Whey and Casein Proteins and Medium-Chain Saturated Fatty Acids from Milk Do Not Increase Low-Grade Inflammation in Abdominally Obese Adults.

PubMed

Bohl, Mette; Bjørnshave, Ann; Gregersen, Søren; Hermansen, Kjeld

2016-01-01

Low-grade inflammation is involved in the development of diabetes and cardiovascular disease (CVD). Inflammation can be modulated by dietary factors. Dairy products are rich in saturated fatty acids (SFA), which are known to possess pro-inflammatory properties. However, different fatty acid compositions may exert different effects. Other components such as milk proteins may exert anti-inflammatory properties which may compensate for the potential negative effects of SFAs. Generally, the available data suggest a neutral role of dairy product consumption on inflammation. To investigate the effects of, and potential interaction between, a dietary supplementation with whey protein and milk fat, naturally enriched in medium-chain SFA (MC-SFA), on inflammatory markers in abdominal obese adults. The study was a 12-week, randomized, double-blinded, intervention study. Sixty-three adults were equally allocated to one of four groups which received a supplement of either 60 g/day whey or 60 g/day casein plus 63 g/day milk fat either high or low in MC-SFA content. Fifty-two subjects completed the study. Before and after the intervention, changes in plasma interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA), high-sensitive C-reactive protein (hsCRP), adiponectin, and monocyte chemoattractant protein-1 (MCP-1) were measured. Changes in inflammatory genes in the subcutaneous adipose tissue were also documented. There were no differences in circulating inflammatory markers between protein types or fatty acid compositions in abdominally obese subjects, with the exception of an increase in adiponectin in response to high compared to low MC-SFA consumption in women. We found that combined dairy proteins and MC-SFAs influenced inflammatory gene expression in adipose tissue, while no effect was detected by dairy proteins or MC-SFA per se. Whey protein compared with casein and MC-SFA-enriched milk fat did not alter circulating markers of low-grade inflammation in abdominally obese subjects, except for an increase in circulating adiponectin in response to high MC-SFA in abdominally obese women.

Cruciferous vegetable intake is inversely correlated with circulating levels of proinflammatory markers in women.

PubMed

Jiang, Yu; Wu, Sheng-Hui; Shu, Xiao-Ou; Xiang, Yong-Bing; Ji, Bu-Tian; Milne, Ginger L; Cai, Qiuyin; Zhang, Xianglan; Gao, Yu-Tang; Zheng, Wei; Yang, Gong

2014-05-01

Higher intakes of cruciferous vegetables or their constituents have been shown to lower inflammation in animal studies. However, evidence for this anti-inflammatory effect of cruciferous vegetable consumption in humans is scarce. In this cross-sectional analysis, we evaluated associations of vegetable intake with a panel of inflammatory and oxidative stress markers among 1,005 middle-aged Chinese women. Dietary intake of foods was assessed by a food frequency questionnaire. Multivariable-adjusted circulating concentrations of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), and IL-6 were lower among women with higher intakes of cruciferous vegetables. The differences in concentrations of inflammatory biomarkers between extreme quintiles of cruciferous vegetable intake were 12.66% for TNF-α (Ptrend=0.01), 18.18% for IL-1β (Ptrend=0.02), and 24.68% for IL-6 (Ptrend=0.02). A similar, but less apparent, inverse association was found for intakes of all vegetables combined but not for noncruciferous vegetables. Levels of the urinary oxidative stress markers F2-isoprostanes and their major metabolite, 2,3-dinor-5,6-dihydro-15-F2t-IsoP, were not associated with intakes of cruciferous vegetables or all vegetables combined. This study suggests that the previously observed health benefits of cruciferous vegetable consumption may be partly associated with the anti-inflammatory effects of these vegetables. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Evaluation of Chitotriosidase as a Marker of Inflammatory Status in Critical Limb Ischemia.

PubMed

Ciocan, Răzvan A; Drugan, Cristina; Gherman, Claudia D; Cătană, Cristina-Sorina; Ciocan, Andra; Drugan, Tudor C; Bolboacă, Sorana D

2017-11-01

Chitotriosidase is an enzyme secreted by activated macrophages. This study aims to investigate the usefulness of circulating chitotriosidase activity as a marker of inflammatory status in patients with critical limb ischemia (CLI). An observational gender-matched case-control study was conducted on patients hospitalized with the primary diagnosis of CLI, as well as a control group. The control group consisted of healthy volunteers. Forty-three patients were included in each group. Similar demographic characteristics (median age of 60-62 years and overweight) were observed in both groups. Chitotriosidase activity ranged from 110 nmol/ml/hr to 1530 nmol/ml/hr in the CLI group and from 30 nmol/ml/hr to 440 nmol/ml/hr in the control group; demonstrating significantly elevated values in the CLI group ( p <0.001). Median plasma chitotriosidase activity was significantly elevated in smokers compared with non-smokers in both groups ( p <0.05). However, this activity had higher values in CLI than in control subjects. Receiver operating characteristic (ROC) analysis was then performed in order to verify the diagnostic accuracy of chitotriosidase as an inflammatory biomarker in CLI. Circulating chitotriosidase is a test which can potentially be used for the monitoring of CLI patients without other inflammatory conditions. However, the interpretation of elevated values must take into account the inflammatory response induced by tobacco exposure. © 2017 by the Association of Clinical Scientists, Inc.

Regular exercise during haemodialysis promotes an anti-inflammatory leucocyte profile

PubMed Central

Dungey, Maurice; Young, Hannah M L; Churchward, Darren R; Burton, James O; Smith, Alice C

2017-01-01

Abstract Background Cardiovascular disease is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leucocyte phenotypes. Methods Twenty-two HD patients from a centre where intradialytic cycling was offered thrice weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at rating of perceived exertion of ‘somewhat hard’. Baseline characteristics were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leucocyte phenotypes were assessed again after 6 months of regular exercise. Results Patients were less active than their healthy counterparts and had significant elevations in measures of inflammation [interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), intermediate and non-classical monocytes; all P < 0.001]. Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months, the proportion of intermediate monocytes in the exercising patients reduced compared with non-exercisers (7.58 ± 1.68% to 6.38 ± 1.81% versus 6.86 ± 1.45% to 7.88 ± 1.66%; P < 0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P < 0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations. Conclusions These findings suggest that regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of cardiovascular disease and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes. PMID:29225811

Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: effects of pioglitazone and metformin treatment.

PubMed

Ciaraldi, Theodore P; Aroda, Vanita; Mudaliar, Sunder R; Henry, Robert R

2013-11-01

Chronic low-grade inflammation is a common feature of insulin resistant states, including obesity and type 2 diabetes. Less is known about inflammation in Polycystic Ovary Syndrome (PCOS). Thus we evaluated the impact of PCOS on circulating cytokine levels and the effects of anti-diabetic therapies on insulin action, cytokine and chemokine levels and inflammatory signaling in skeletal muscle. Twenty subjects with PCOS and 12 healthy normal cycling (NC) subjects of similar body mass index were studied. PCOS subjects received oral placebo or pioglitazone, 45 mg/d, for 6 months. All PCOS subjects then had metformin, 2 g/day, added to their treatment. Circulating levels of cytokines, chemokines, and adiponectin, skeletal muscle markers of inflammation and phosphorylation of signaling proteins, insulin action evaluated by the hyperinsulinemic/euglycemic clamp procedure and Homeostasis Model Assessment of Insulin Resistance were measured. Circulating levels of a number of cytokines and chemokines were generally similar between PCOS and NC subjects. Levels in PCOS subjects were not altered by pioglitazone or metformin treatment, even though whole body insulin action and adiponectin levels increased with pioglitazone. In spite of the lack of change in levels of cytokines and chemokines, several markers of inflammation in skeletal muscle were improved with Pio treatment. PCOS may represent a state of elevated sensitivity of inflammatory cells in skeletal muscle to cytokines and chemokines, a property that could be reversed by pioglitazone treatment together with improved insulin action. © 2013.

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury.

PubMed

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-12-04

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q(-/-)) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q(-/-) mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury*

PubMed Central

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-01-01

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q−/−) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q−/− mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. PMID:26487714

Circulating Endothelial Progenitor Cells Present an Inflammatory Phenotype and Function in Patients With Alcoholic Liver Cirrhosis

PubMed Central

Kaur, Savneet; Sehgal, Rashi; Shastry, Saggere M.; McCaughan, Geoffrey; McGuire, Helen M.; Fazekas St de Groth, Barbara; Sarin, Shiv; Trehanpati, Nirupma; Seth, Devanshi

2018-01-01

Background and Aim: Endothelial progenitor cells (EPCs) have been implicated in liver injury and repair. However, the phenotype and potential of these heterogenous EPCs remain elusive. In particular, their involvement in the pathogenesis of alcoholic liver cirrhosis (ALC) remains unclear. The current study extensively characterized the phenotype and functions of EPCs to understand their role in ALC pathogenesis. Methods: Circulating EPCs were identified as CD34+CD133+CD31+ cells by flow cytometer in ALC patients (n = 7) and healthy controls (HC, n = 7). A comprehensive characterization of circulating EPCs using more than 30 phenotype markers was performed by mass cytometer time of flight (CyTOF) in an independent cohort of age and gender matched ALC patients (n = 4) and controls (n = 5). Ex vivo cultures of circulating EPCs from ALC patients (n = 20) and controls (n = 18) were also tested for their functions, including colony formation, LDL uptake, lectin binding and cytokine secretion (ELISA). Results: Three distinct populations of circulating EPCs (CD34+CD133+CD31+) were identified, classified on their CD45 expression (negative: CD45−; intermediate: CD45int; high: CD45hi). CD45int and CD45hi EPCs significantly increased in ALC patients compared to controls (p-val = 0.006). CyTOF data showed that CD45hi EPCs were distinct from CD45− and CD45int EPCs, with higher expression of T cell and myeloid markers, including CD3, CD4, HLA-DR, and chemokine receptors, CCR2, CCR5, CCR7, and CX3CR1. Similar to circulating EPCs, percentage of CD45hiCD34+CD31+ EPCs in ex-vivo cultures from patients, were significantly higher compared to controls (p < 0.05). Cultured EPCs from patients also showed increased LDL uptake, lectin binding and release of TNF-alpha, RANTES, FGF-2, and VEGF. Conclusions: We report the first extensive characterization of circulating human EPCs with distinct EPC subtypes. Increase in CD45hi EPC subtype in ALC patients with enhanced functions, inflammatory cytokines and angiogenic mediators in patients suggests an inflammatory role for these cells in ALC. PMID:29872403

Host response biomarkers in the diagnosis of sepsis: a general overview.

PubMed

Parlato, Marianna; Cavaillon, Jean-Marc

2015-01-01

Critically ill patients who display a systemic inflammatory response syndrome (SIRS) are prone to develop nosocomial infections. The challenge remains to distinguish as early as possible among SIRS patients those who are developing sepsis. Following a sterile insult, damage-associated molecular patterns (DAMPs) released by damaged tissues and necrotic cells initiate an inflammatory response close to that observed during sepsis. During sepsis, pathogen-associated molecular patterns (PAMPs) trigger the release of host mediators involved in innate immunity and inflammation through identical receptors as DAMPs. In both clinical settings, a compensatory anti-inflammatory response syndrome (CARS) is concomitantly initiated. The exacerbated production of pro- or anti-inflammatory mediators allows their detection in biological fluids and particularly within the bloodstream. Some of these mediators can be used as biomarkers to decipher among the patients those who developed sepsis, and eventually they can be used as prognosis markers. In addition to plasma biomarkers, the analysis of some surface markers on circulating leukocytes or the study of mRNA and miRNA can be helpful. While there is no magic marker, a combination of few biomarkers might offer a high accuracy for diagnosis.

[Antioxidant and anti-inflammatory modulation of exercise during aging].

PubMed

Galle, Fernando Alexis; Martella, Diana; Bresciani, Guilherme

2018-06-10

Aging is characterised by a gradual loss of the functional reserve. This, along with the fostering of sedentary habits and the increase in risk factors, causes a deterioration of antioxidant defences and an increase of the circulatory levels of inflammatory and oxidative markers, boosting a low-rate chronic inflammation, defined as inflamm-aging. This phenomenon is present in the aetiopathology of chronic diseases, as well as in cognitive deterioration cases associated with aging. The objective of this review is to describe the modulation of antioxidant and anti-inflammatory effects of physical exercise of moderate intensity and volume in the elderly. Evidence of its effectiveness as a non-pharmacological resource is presented, which decreases some deleterious effects of aging. This is mainly due to its neuroprotective action, the increase in circulating anti-inflammatory markers, and the improvement of antioxidant defence derived from its practice. Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

A life course approach to explore the biological embedding of socioeconomic position and social mobility through circulating inflammatory markers.

PubMed

Castagné, Raphaële; Delpierre, Cyrille; Kelly-Irving, Michelle; Campanella, Gianluca; Guida, Florence; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Kyrtopoulos, Soterios; Hosnijeh, Fatemeh Saberi; Lang, Thierry; Vermeulen, Roel; Vineis, Paolo; Stringhini, Silvia; Chadeau-Hyam, Marc

2016-04-27

Lower socioeconomic position (SEP) has consistently been associated with poorer health. To explore potential biological embedding and the consequences of SEP experiences from early life to adulthood, we investigate how SEP indicators at different points across the life course may be related to a combination of 28 inflammation markers. Using blood-derived inflammation profiles measured by a multiplex array in 268 participants from the Italian component of the European Prospective Investigation into Cancer and Nutrition cohort, we evaluate the association between early life, young adulthood and later adulthood SEP with each inflammatory markers separately, or by combining them into an inflammatory score. We identified an increased inflammatory burden in participants whose father had a manual occupation, through increased plasma levels of CSF3 (G-CSF; β = 0.29; P = 0.002), and an increased inflammatory score (β = 1.96; P = 0.029). Social mobility was subsequently modelled by the interaction between father's occupation and the highest household occupation, revealing a significant difference between "stable Non-manual" profiles over the life course versus "Manual to Non-manual" profiles (β = 2.38, P = 0.023). Low SEP in childhood is associated with modest increase in adult inflammatory burden; however, the analysis of social mobility suggests a stronger effect of an upward social mobility over the life course.

Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation.

PubMed

Melek, Flora Eli; Baroncini, Liz Andréa Villela; Repka, João Carlos Domingus; Nascimento, Celso Soares; Précoma, Dalton Bertolim

2012-01-01

Thiobarbituric acid-reactive substance is a marker of oxidative stress and has cytotoxic and genotoxic actions. C- reactive protein is used to evaluate the acute phase of inflammatory response. To assess the thiobarbituric acid-reactive substance and C-reactive protein levels during extracorporeal circulation in patients submitted to cardiopulmonary bypass. Twenty-five consecutive surgical patients (16 men and nine women; mean age 61.2 ± 9.7 years) with severe coronary artery disease diagnosed by angiography scheduled for myocardial revascularization surgery with extracorporeal circulation were selected. Blood samples were collected immediately before initializing extracorporeal circulation, T0; in 10 minutes, T10; and in 30 minutes, T30. The thiobarbituric acid-reactive substance levels increased after extracorporeal circulation (P=0.001), with average values in T0=1.5 ± 0.07; in T10=5.54 ± 0.35; and in T30=3.36 ± 0.29 mmoles/mg of serum protein. The C-reactive protein levels in T0 were negative in all samples; in T10 average was 0.96 ± 0.7 mg/dl; and in T30 average was 0.99 ± 0.76 mg/dl. There were no significant differences between the dosages in T10 and T30 (P=0.83). C-reactive protein and thiobarbituric acid-reactive substance plasma levels progressively increased during extracorporeal circulation, with maximum values of thiobarbituric acid-reactive substance at 10 min and of C-reactive protein at 30 min. It suggests that there are an inflammatory response and oxidative stress during extracorporeal circulation.

Sickle Cell Vaso-occlusive Crisis Induces the Release of Circulating Serum Heat Shock Protein-70

PubMed Central

Adewoye, Adeboye H.; Klings, Elizabeth S.; Farber, Harrison W.; Palaima, Elizabeth; Bausero, Maria A.; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H.; Asea, Alexzander

2006-01-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P < 0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P < 0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD. PMID:15726596

Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70.

PubMed

Adewoye, Adeboye H; Klings, Elizabeth S; Farber, Harrison W; Palaima, Elizabeth; Bausero, Maria A; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H; Asea, Alexzander

2005-03-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD.

Adiponectin, interleukin-6, monocyte chemoattractant protein-1, and regional fat mass during 12-month randomized treatment with metformin and/or oral contraceptives in polycystic ovary syndrome.

PubMed

Glintborg, Dorte; Mumm, Hanne; Altinok, Magda Lambaa; Richelsen, Bjørn; Bruun, Jens Meldgaard; Andersen, Marianne

2014-08-01

Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. To evaluate if improved body composition during treatment with metformin (M) vs. oral contraceptive pills (OCP) was associated with changes in circulating adiponectin, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Ninety patients with PCOS were randomized to 12-month treatment with M (2 g/day), M + OCP (150 mg desogestrel + 30 microgram ethinylestradiol) or OCP. Adiponectin, IL-6, MCP-1, whole body DXA scans, and clinical evaluations were performed before and after the intervention period in the 65 study completers. Changes in inflammatory markers and changes in total and regional fat mass estimates. Adiponectin, IL-6, and MCP-1 levels were unchanged during the three types of medical intervention. Treatment with M and M + OCP was superior to OCP regarding decreased regional fat mass. Baseline adiponectin and IL-6 were associated with BMI, waist, and trunk fat mass. Changes in trunk fat were significantly associated with changes in IL-6 and MCP-1 during M + OCP. Long-term treatment with M alone or in combination with OCP was associated with improved body composition compared to OCP, whereas inflammatory markers were unchanged. OCP was not associated with increased inflammatory markers despite a small but significant weight gain.

H2S dependent and independent anti-inflammatory activity of zofenoprilat in cells of the vascular wall.

PubMed

Monti, Martina; Terzuoli, Erika; Ziche, Marina; Morbidelli, Lucia

2016-11-01

Cardiovascular diseases as atherosclerosis are associated to an inflammatory state of the vessel wall which is accompanied by endothelial dysfunction, and adherence and activation of circulating inflammatory cells. Hydrogen sulfide, a novel cardiovascular protective gaseous mediator, has been reported to exert anti-inflammatory activity. We have recently demonstrated that the SH containing ACE inhibitor zofenoprilat, the active metabolite of zofenopril, controls the angiogenic features of vascular endothelium through H 2 S enzymatic production by cystathionine gamma lyase (CSE). Based on H 2 S donor/generator property of zofenoprilat, the objective of this study was to evaluate whether zofenoprilat exerts anti-inflammatory activity in vascular cells through its ability to increase H 2 S availability. Here we found that zofenoprilat, in a CSE/H 2 S-mediated manner, abolished all the inflammatory features induced by interlukin-1beta (IL-1β) in human umbilical vein endothelial cells (HUVEC), especially the NF-κB/cyclooxygenase-2 (COX-2)/prostanoid biochemical pathway. The pre-incubation with zofenoprilat/CSE dependent H 2 S prevented IL-1β induced paracellular hyperpermeability through the control of expression and localization of cell-cell junctional markers ZO-1 and VE-cadherin. Moreover, zofenoprilat/CSE dependent H 2 S reduced the expression of the endothelial markers CD40 and CD31, involved in the recruitment of circulating mononuclear cells and platelets. Interestingly, this anti-inflammatory activity was also confirmed in vascular smooth muscle cells and fibroblasts as zofenoprilat reduced, in both cell lines, proliferation, migration and COX-2 expression induced by IL-1β, but independently from the SH moiety and H 2 S availability. These in vitro data document the anti-inflammatory activity of zofenoprilat on vascular cells, reinforcing the cardiovascular protective effect of this multitasking drug. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patterns of Circulating Inflammatory Biomarkers in Older Persons with Varying Levels of Physical Performance: A Partial Least Squares-Discriminant Analysis Approach

PubMed Central

Marzetti, Emanuele; Landi, Francesco; Marini, Federico; Cesari, Matteo; Buford, Thomas W.; Manini, Todd M.; Onder, Graziano; Pahor, Marco; Bernabei, Roberto; Leeuwenburgh, Christiaan; Calvani, Riccardo

2014-01-01

Background: Chronic, low-grade inflammation and declining physical function are hallmarks of the aging process. However, previous attempts to correlate individual inflammatory biomarkers with physical performance in older people have produced mixed results. Given the complexity of the inflammatory response, the simultaneous analysis of an array of inflammatory mediators may provide more insights into the relationship between inflammation and age-related physical function decline. This study was designed to explore the association between a panel of inflammatory markers and physical performance in older adults through a multivariate statistical approach. Methods: Community-dwelling older persons were categorized into “normal walkers” (NWs; n = 27) or “slow walkers” (SWs; n = 11) groups using 0.8 m s−1 as the 4-m gait speed cutoff. A panel of 14 circulating inflammatory biomarkers was assayed by multiplex analysis. Partial least squares-discriminant analysis (PLS-DA) was used to identify patterns of inflammatory mediators associated with gait speed categories. Results: The optimal complexity of the PLS-DA model was found to be five latent variables. The proportion of correct classification was 88.9% for NW subjects (74.1% in cross-validation) and 90.9% for SW individuals (81.8% in cross-validation). Discriminant biomarkers in the model were interleukin 8, myeloperoxidase, and tumor necrosis factor alpha (all higher in the SW group), and P-selectin, interferon gamma, and granulocyte–macrophage colony-stimulating factor (all higher in the NW group). Conclusion: Distinct profiles of circulating inflammatory biomarkers characterize older subjects with different levels of physical performance. The dissection of these patterns may provide novel insights into the role played by inflammation in the disabling cascade and possible new targets for interventions. PMID:25593902

Circulating FABP4 is a marker of metabolic and cardiovascular risk in SLE patients.

PubMed

Parra, S; Cabré, A; Marimon, F; Ferré, R; Ribalta, J; Gonzàlez, M; Heras, M; Castro, A; Masana, L

2014-03-01

The aim of this study is to determine if circulating fatty acid-binding protein 4 (FABP4) plasma levels are a possible marker of metabolic risk in SLE patients. Circulating levels of adipose FABP4 are associated with adiposity, insulin resistance (IR), metabolic syndrome, diabetes and cardiovascular diseases. Patients affected by systemic lupus erythematosus (SLE) show an accelerated atherosclerosis that cannot be entirely explained by traditional cardiovascular risk factors. Sixty consecutive patients with SLE and 34 non-SLE age-matched controls were recruited for the study. Total plasma lipids and circulating FABP4 were determined. Subclinical atherosclerosis was evaluated by measuring carotid intimae-media thickness (c-IMT) by sonography, and the distribution of lipoprotein subclasses was analysed by nuclear magnetic resonance (NMR) spectroscopy. In the SLE group, FABP4 was associated with IR, atherogenic dyslipidaemia, as measured by NMR, and the presence of subclinical atherosclerosis. In multivariate analyses FABP4 was associated with increased c-IMT independent of the inflammatory state of the patient. In sum, circulating FABP4 is involved in the metabolic disturbances of SLE affecting lipid metabolism and IR, and it could be a biomarker of atherosclerosis in this population.

Childhood maltreatment and inflammatory markers: a systematic review.

PubMed

Coelho, R; Viola, T W; Walss-Bass, C; Brietzke, E; Grassi-Oliveira, R

2014-03-01

Childhood maltreatment (CM) has been associated with several diseases in adult life, including diabetes, obesity and mental disorders. Inflammatory conditions have been postulated as possible mediators of this relationship. The aim was to conduct a systematic review regarding the association between CM and inflammatory markers in adulthood. A literature search of the PubMed, ISI, EMBASE and PsychINFO databases was conducted. The key terms used were as follows: 'Child Maltreatment', 'Childhood Trauma', 'Early Life Stress', 'Psychological Stress', 'Emotional Stress', 'Child Abuse' and 'Child Neglect'. They were cross-referenced separately with the terms: 'C-reactive Protein (CRP)', 'Tumor Necrosis Factor', 'Cytokine', 'Interleukin', 'Inflammatory' and 'Inflammation'. Twenty articles remained in the review after exclusion criteria were applied. Studies showed that a history of CM was associated with increased levels of CRP, fibrinogen and proinflammatory cytokines. Increased levels of circulating CRP in individuals with a history of CM were the most robust finding among the studies. Data about anti-inflammatory mediators are still few and inconsistent. Childhood maltreatment is associated with a chronic inflammatory state independent of clinical comorbidities. However, studies are heterogeneous regarding CM assessment and definition. Important methodological improvements are needed to better understand the potential impact of CM on inflammatory response. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A life course approach to explore the biological embedding of socioeconomic position and social mobility through circulating inflammatory markers

PubMed Central

Castagné, Raphaële; Delpierre, Cyrille; Kelly-Irving, Michelle; Campanella, Gianluca; Guida, Florence; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Kyrtopoulos, Soterios; Hosnijeh, Fatemeh Saberi; Lang, Thierry; Vermeulen, Roel; Vineis, Paolo; Stringhini, Silvia; Chadeau-Hyam, Marc

2016-01-01

Lower socioeconomic position (SEP) has consistently been associated with poorer health. To explore potential biological embedding and the consequences of SEP experiences from early life to adulthood, we investigate how SEP indicators at different points across the life course may be related to a combination of 28 inflammation markers. Using blood-derived inflammation profiles measured by a multiplex array in 268 participants from the Italian component of the European Prospective Investigation into Cancer and Nutrition cohort, we evaluate the association between early life, young adulthood and later adulthood SEP with each inflammatory markers separately, or by combining them into an inflammatory score. We identified an increased inflammatory burden in participants whose father had a manual occupation, through increased plasma levels of CSF3 (G-CSF; β = 0.29; P = 0.002), and an increased inflammatory score (β = 1.96; P = 0.029). Social mobility was subsequently modelled by the interaction between father’s occupation and the highest household occupation, revealing a significant difference between “stable Non-manual” profiles over the life course versus “Manual to Non-manual” profiles (β = 2.38, P = 0.023). Low SEP in childhood is associated with modest increase in adult inflammatory burden; however, the analysis of social mobility suggests a stronger effect of an upward social mobility over the life course. PMID:27117519

Effects of Olive Oil Phenolic Compounds on Inflammation in the Prevention and Treatment of Coronary Artery Disease

PubMed Central

de Souza, Priscilla Azambuja Lopes; Marcadenti, Aline; Portal, Vera Lúcia

2017-01-01

Coronary artery disease (CAD) is responsible for more than 7 million deaths worldwide. In the early stages of the development of atherosclerotic plaques, cardiovascular risk factors stimulate vascular endothelial cells, initiating an inflammatory process, fundamental in the pathogenesis of CAD. The inclusion of potentially cardioprotective foods, such as olive oil, to the diet, may aid in the control of these risk factors, and in the reduction of cytokines and inflammatory markers. The present review aims to address the interaction between phenolic compounds present in olive oil, and inflammation, in the prevention and treatment of CAD. In vitro and in vivo studies suggest that phenolic compounds, such as hydroxytyrosol, tyrosol, and their secoiridoid derivatives, may reduce the expression of adhesion molecules and consequent migration of immune cells, modify the signaling cascade and the transcription network (blocking the signal and expression of the nuclear factor kappa B), inhibit the action of enzymes responsible for the production of eicosanoids, and consequently, decrease circulating levels of inflammatory markers. Daily consumption of olive oil seems to modulate cytokines and inflammatory markers related to CAD in individuals at risk for cardiovascular diseases. However, clinical studies that have evaluated the effects of olive oil and its phenolic compounds on individuals with CAD are still scarce. PMID:28973999

Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

PubMed

Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

2015-01-01

Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

Emotional Processes in Patients Undergoing Coronary Artery Bypass Graft Surgeries with Extracorporeal Circulation in View of Selected Indicators of the Inflammatory Condition

PubMed Central

Płotek, Włodzimierz; Pielok, Joanna; Cybulski, Marcin; Samborska, Regina

2015-01-01

Background The aim of this study was to describe positive and negative emotions in patients undergoing coronary artery bypass graft (CABG) surgeries with extracorporeal circulation and the correlations between emotions and basic indicators of the inflammatory condition: C-reactive protein (CRP) concentration, body temperature, and leukocyte count. Material/Methods Standardized tools were used to select 52 patients (aged 47–63 years, 6 women – 11.5% and 46 men – 88.5%) without dementia or depression. The Positive and Negative Affect Schedule (PANAS) was used to examine positive affect (PA) and negative affect (NA) and the State-Trait Anxiety Inventory (STAI X1 and X2) was used to examine the anxiety level. The patients underwent CABG surgery according to a common anesthesia protocol and for 5 consecutive days they were observed in the ward, where selected indicators of the inflammatory condition were monitored. Results A detailed description of the results of examinations of emotions was presented. The patients with low PA-trait level, high NA-trait level, and high anxiety-trait level (STAI X2) exhibited statistically significantly higher body temperatures than the other patients in the postoperative period. The patients with high NA-trait and anxiety-state levels (STAI X1) had statistically significantly lower CRP levels in the postoperative period than the patients with low NA-trait and anxiety-state levels (STAI X1). Conclusions Patients undergoing CABG operations express both positive and negative affects. The changes in the inflammatory markers are expressed mostly by CRP concentration. There exist relationships between the result of tests assessing emotions and the markers of the inflammatory condition. PMID:25573296

Links demystified: Periodontitis and cancer

PubMed Central

Pendyala, Gowri; Joshi, Saurabh; Chaudhari, Shantanu; Gandhage, Dhananjay

2013-01-01

Cancer is marked by the uncontrolled growth of cells, tissue invasion and metastasis to various organs via the circulatory and lymphatic systems. Recent data have expanded the concept that inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. The tumor microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival, and migration. Periodontal disease, a chronic inflammatory condition is characterized by an oral bacterial infection leading to inflammation within the supporting tissues of the teeth, which often leads to the destruction of the periodontal tissues and alveolar bone that support the teeth. This oral inflammation often has systemic effects leading to an increased concentration of circulating inflammatory markers with the severity of disease being correlated directly with levels of serum inflammatory markers. Periodontal infection has been linked to organ and systemic diseases. There is documented evidence of significant associations between cancer of the lung, kidney, pancreas, hematological and oral cancers, and periodontal disease. This articles reviews and summarizes the possible biological mechanisms involved between periodontal infection and cancer. PMID:24379856

Links demystified: Periodontitis and cancer.

PubMed

Pendyala, Gowri; Joshi, Saurabh; Chaudhari, Shantanu; Gandhage, Dhananjay

2013-11-01

Cancer is marked by the uncontrolled growth of cells, tissue invasion and metastasis to various organs via the circulatory and lymphatic systems. Recent data have expanded the concept that inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. The tumor microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival, and migration. Periodontal disease, a chronic inflammatory condition is characterized by an oral bacterial infection leading to inflammation within the supporting tissues of the teeth, which often leads to the destruction of the periodontal tissues and alveolar bone that support the teeth. This oral inflammation often has systemic effects leading to an increased concentration of circulating inflammatory markers with the severity of disease being correlated directly with levels of serum inflammatory markers. Periodontal infection has been linked to organ and systemic diseases. There is documented evidence of significant associations between cancer of the lung, kidney, pancreas, hematological and oral cancers, and periodontal disease. This articles reviews and summarizes the possible biological mechanisms involved between periodontal infection and cancer.

A Double-Blinded Randomized Study Investigating a Possible Anti-Inflammatory Effect of Saxagliptin versus Placebo as Add-On Therapy in Patients with Both Type 2 Diabetes And Stable Coronary Artery Disease.

PubMed

Njerve, Ida Unhammer; Åkra, Sissel; Weiss, Thomas W; Solheim, Svein; Øvstebø, Reidun; Aass, Hans Christian D; Byrkjeland, Rune; Arnesen, Harald; Seljeflot, Ingebjørg

2017-01-01

Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM. Patients ( n = 12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at -150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR). HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo ( p = 0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group ( p = 0.043, both), significantly different from that in the placebo ( p = 0.009 and p = 0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers. In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies.

Grape Consumption Increases Anti-Inflammatory Markers and Upregulates Peripheral Nitric Oxide Synthase in the Absence of Dyslipidemias in Men with Metabolic Syndrome

PubMed Central

Barona, Jacqueline; Blesso, Christopher N.; Andersen, Catherine J.; Park, Youngki; Lee, Jiyoung; Fernandez, Maria Luz

2012-01-01

We evaluated the effects of grape consumption on inflammation and oxidation in the presence or absence of dyslipidemias in metabolic syndrome (MetS). Men with MetS (n = 24), 11 with high triglycerides and low HDL and 13 with no dyslipidemia were recruited and randomly allocated to consume daily either 46 g of lyophilized grape powder (GRAPE), equivalent to 252 g fresh grapes, or placebo with an identical macronutrient composition and caloric value as GRAPE for four weeks. After a three-week washout, participants followed the alternate treatment. We measured changes between placebo and GRAPE periods in inflammatory and oxidative stress markers both in circulation and in gene expression. Changes in plasma adiponectin (p < 0.05), interleukin (IL)-10 (p < 0.005) and in mRNA expression of the inducible isoform of nitric oxide synthase (iNOS) (p < 0.25) were increased in the GRAPE compared to the placebo period only in those individuals without dyslipidemia. Additionally, plasma IL-10 was negatively correlated with NOX2 expression, a marker of oxidative stress (r = −0.55, p < 0.01), while iNOS expression was positively correlated with the expression of superoxide dismutase 2 (r = 0.642, p < 0.01), a key anti-oxidative enzyme. Grape consumption displayed anti-oxidative and increased anti-inflammatory markers in the absence of the inflammatory milieu associated with dyslipidemias. PMID:23222963

Social relationships and inflammatory markers: an analysis of Taiwan and the U.S.

PubMed

Glei, Dana A; Goldman, Noreen; Ryff, Carol D; Lin, Yu-Hsuan; Weinstein, Maxine

2012-06-01

We evaluated the association between two aspects of social relationships and six inflammatory markers in Taiwan and the U.S. These two countries share similar levels of current life expectancy, but exhibit important differences in social structure. The data comprised population based samples from Taiwan (aged 53+; n=962) and the U.S. (aged 35-86; n=990) collected between 2003 and 2009. Circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and soluble forms of intercellular adhesion molecule 1, E-selectin, and IL-6 receptor (sIL-6R) were measured in fasting blood samples. A social integration score was based on marital status, contact with family and friends, church attendance, and other social participation. A perceived social support index was based on questions regarding the availability of care and support from family and friends. Linear regression models tested the association between these two measures and each inflammatory marker controlling for sociodemographic characteristics, obesity, medication use, and baseline health status. After adjusting for potential confounders, social integration had a significant but weak inverse association with CRP in Taiwan. Perceived social support was significant in two of 12 models, and the coefficient was positive (i.e., higher support was associated with higher CRP and sIL-6R in the U.S.). We found no evidence that the coefficients for social relationship measures varied by sex or age. Our results yielded limited evidence of a weak association between two dimensions of social relationships and six inflammatory markers in Taiwan and the U.S. Given that the literature suggests a strong link between social relationships and mortality, and that inflammation plays an important role in the leading causes of death, we had expected to find consistent and moderately strong associations between social relationships and inflammatory markers. The small effect sizes and lack of robustness across markers were surprising. Copyright © 2012 Elsevier Ltd. All rights reserved.

Social Relationships and Inflammatory Markers: An Analysis of Taiwan and the U.S.

PubMed Central

Glei, Dana A.; Goldman, Noreen; Ryff, Carol D.; Lin, Yu-Hsuan; Weinstein, Maxine

2012-01-01

We evaluated the association between two aspects of social relationships and six inflammatory markers in Taiwan and the U.S. These two countries share similar levels of current life expectancy, but exhibit important differences in social structure. The data comprised population based samples from Taiwan (aged 53+; n = 962) and the U.S. (aged 35-86; n = 990) collected between 2003 and 2009. Circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and soluble forms of intercellular adhesion molecule 1, E-selectin, and IL-6 receptor (sIL-6R) were measured in fasting blood samples. A social integration score was based on marital status, contact with family and friends, church attendance, and other social participation. A perceived social support index was based on questions regarding the availability of care and support from family and friends. Linear regression models tested the association between these two measures and each inflammatory marker controlling for sociodemographic characteristics, obesity, medication use, and baseline health status. After adjusting for potential confounders, social integration had a significant but weak inverse association with CRP in Taiwan. Perceived social support was significant in two of 12 models, and the coefficient was positive (i.e., higher support was associated with higher CRP and sIL-6R in the U.S.). We found no evidence that the coefficients for social relationship measures varied by sex or age. Our results yielded limited evidence of a weak association between two dimensions of social relationships and six inflammatory markers in Taiwan and the U.S. Given that the literature suggests a strong link between social relationships and mortality, and that inflammation plays an important role in the leading causes of death, we had expected to find consistent and moderately strong associations between social relationships and inflammatory markers. The small effect sizes and lack of robustness across markers were surprising. PMID:22483707

Oxidative stress and inflammatory markers in relation to circulating levels of adiponectin.

PubMed

Gustafsson, Stefan; Lind, Lars; Söderberg, Stefan; Zilmer, Mihkel; Hulthe, Johannes; Ingelsson, Erik

2013-07-01

Previous epidemiological studies together with animal studies have suggested an association between adiponectin and oxidative stress and inflammation, but community-based studies are lacking. Our objective was to investigate the relative importance of oxidative stress and inflammatory markers, representing different pathways in relation to adiponectin. In a cross-sectional sample of 929 70-year-old individuals (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors study, relations between serum adiponectin and oxidative stress [conjugated dienes (CD), homocysteine, total antioxidant capacity, oxidized low-density lipoprotein (OxLDL), OxLDL antibodies, baseline CD of LDL, glutathione (GSH), total glutathione (TGSH), glutathione disulfide], circulation interleukins (IL-6, IL-8), other cytokines [tumor necrosis factor α, monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor], cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, P-selectin, L-selectin), and systemic inflammatory markers [C-reactive protein (CRP), leukocyte count] in separate models were investigated. In age- and sex-adjusted, as well as multivariable-adjusted models, adiponectin was significantly and positively associated with GSH, log TGSH, whereas an inverse association was observed for CD and log EGF. An inverse association between adiponectin and MCP-1, log E-selectin, and log CRP was significant in age- and sex-adjusted models, but not in multivariable-adjusted models. Our results imply that higher levels of adiponectin are associated with a more beneficial oxidative stress profile, with higher levels of principal anti-oxidative GSH and total GSH together with lower levels of lipid peroxidation, possibly through shared pathways. Further studies are needed to investigate whether changes in the oxidative stress profile may be a mechanism linking adiponectin with type 2 diabetes and/or cardiovascular disease. Copyright © 2012 The Obesity Society.

An exploratory factor analysis of inflammatory and coagulation markers associated with femoral artery atherosclerosis in the San Diego Population Study.

PubMed

Egnot, Natalie Suder; Barinas-Mitchell, Emma; Criqui, Michael H; Allison, Matthew A; Ix, Joachim H; Jenny, Nancy S; Wassel, Christina L

2018-04-01

Several biomarkers of inflammation and coagulation have been implicated in lower extremity atherosclerosis. We utilized an exploratory factor analysis (EFA) to identify distinct factors derived from circulating inflammatory and coagulation biomarkers then examined the associations of these factors with measures of lower extremity subclinical atherosclerosis, including the ankle-brachial index (ABI), common and superficial femoral intima-media thickness (IMT), and atherosclerotic plaque presence, burden, and characteristics. The San Diego Population Study (SDPS) is a prospective, community-living, multi-ethnic cohort of 1103 men and women averaged age 70. Regression analysis was used to assess cross-sectional associations between the identified groupings of biomarkers (factors) and the ABI and femoral artery atherosclerosis measurements. Two biomarker factors emerged from the factor analysis. Factor 1 consisting of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen was significantly associated with higher odds (OR = 1.99, p < 0.01) of a borderline ABI value (0.91-0.99), while Factor 2 containing D-dimer and pentraxin (PTX)-3 was significantly associated with higher common femoral artery (CFA) IMT (β = 0.23, p < 0.01) and lower ABI (β = -0.03, p < 0.01). Two groupings of biomarkers were identified via EFA of seven circulating biomarkers of inflammation and coagulation. These distinct groups are differentially associated with markers of lower extremity subclinical atherosclerosis. Our findings suggest that high inflammatory and coagulation burden were better markers of more severe lower-extremity disease as indicated by low ABI rather than early atherosclerotic lesion development in the femoral artery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study

PubMed Central

Williams, Catherine J.; Fargnoli, Jessica L.; Hwang, Janice J.; van Dam, Rob M.; Blackburn, George L.; Hu, Frank B.; Mantzoros, Christos S.

2009-01-01

To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1058 non-diabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank ≥4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 μg/ml, respectively, in diabetic women, P=0.004; 15.0 vs. 13.2 μg/ml in nondiabetic women, P=0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein and tumor necrosis factor-α receptor II. Adjustment for adiponectin did not weaken these associations, nor did adjustment for inflammatory markers attenuate the association between coffee consumption and adiponectin. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations. PMID:18070989

Effects of endurance exercise training on inflammatory circulating progenitor cell content in lean and obese adults.

PubMed

Niemiro, Grace M; Allen, Jacob M; Mailing, Lucy J; Khan, Naiman A; Holscher, Hannah D; Woods, Jeffrey A; De Lisio, Michael

2018-06-19

Chronic inflammation underlies many of the health decrements associated with obesity. Circulating progenitor cells can sense and respond to inflammatory stimuli, increasing the local inflammatory response within tissues. Here we show that 6 weeks of endurance exercise training significantly decreases inflammatory circulating progenitor cells in obese adults. These findings provide novel cellular mechanisms for the beneficial effects of exercise in obese adults. Circulating progenitor cells (CPCs) and subpopulations are normally found in the bone marrow, but can migrate to peripheral tissues to participate in local inflammation and/or remodelling. The purpose of this study was to compare the CPC response, particularly the inflammatory-primed haematopoietic stem and progenitor (HSPC) subpopulation, to a 6 week endurance exercise training (EET) intervention between lean and obese adults. Seventeen healthy weight (age: 23.9 ± 5.4 years, body mass index (BMI): 22.0 ± 2.6 kg m -2 ) and 10 obese (age: 29.0 ± 8.0 years, BMI: 33.1 ± 6.0 kg m -2 ) previously sedentary adults participated in an EET. Blood was collected before and after EET for quantification of CPCs and subpopulations via flow cytometry, colony forming unit assays and plasma concentrations of C-X-C motif chemokine 12 (CXCL12), granulocyte-colony stimulating factor (G-CSF), and chemokine (C-C motif) ligand 2 (CCL2). Exercise training reduced the number of circulating HSPCs and adipose tissue-derived mesenchymal stem cells (AT-MSCs). EET increased the colony forming potential of granulocytes and macrophages irrespective of BMI. EET reduced the number of HSPCs expressing the chemokine receptor CCR2 and the pro-inflammatory marker TLR4. EET-induced changes in adipose tissue-derived MSCs and bone marrow-derived MSCs were negatively related to changes in absolute fitness. Our results indicate that EET, regardless of BMI status, decreases CPCs and subpopulations, particularly those primed for contribution to tissue inflammation. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population.

PubMed

Coen, Paul M; Flynn, Michael G; Markofski, Melissa M; Pence, Brandt D; Hannemann, Robert E

2010-12-01

Statin treatment and exercise training can reduce markers of inflammation when administered separately. The purpose of this study was to determine the effect of rosuvastatin treatment and the addition of exercise training on circulating markers of inflammation including C-reactive protein (CRP), monocyte toll-like receptor 4 (TLR4) expression, and CD14+CD16+ monocyte population size. Thirty-three hypercholesterolemic and physically inactive subjects were randomly assigned to rosuvastatin (R) or rosuvastatin/exercise (RE) groups. A third group of physically active hypercholesterolemic subjects served as a control (AC). The R and RE groups received rosuvastatin treatment (10 mg/d) for 20 weeks. From week 10 to week 20, the RE group also participated in an exercise training program (3d/wk). Measurements were made at baseline (Pre), week 10 (Mid), and week 20 (Post), and included TLR4 expression on CD14+ monocytes and CD14+CD16+ monocyte population size as determined by 3-color flow cytometry. Serum CRP was quantified by enzyme-linked immunosorbent assay. TLR4 expression on CD14+ monocytes was higher in the R group at week 20. When treatment groups (R and RE) were combined, serum CRP was lower across time. Furthermore, serum CRP and inflammatory monocyte population size were lower in the RE group compared with the R group at the Post time point. When all groups (R, RE, and AC) were combined, TLR4 expression was greater on inflammatory monocytes (CD14+CD16+) compared with classic monocytes (CD14+CD16⁻) at all time points. In conclusion, rosuvastatin may influence monocyte inflammatory response by increasing TLR4 expression on circulating monocytes. The addition of exercise training to rosuvastatin treatment further lowered CRP and reduced the size of the inflammatory monocyte population, suggesting an additive anti-inflammatory effect of exercise. Copyright © 2010 Elsevier Inc. All rights reserved.

Childhood trauma and parental style: Relationship with markers of inflammation, oxidative stress, and aggression in healthy and personality disordered subjects.

PubMed

Fanning, Jennifer R; Lee, Royce; Gozal, David; Coussons-Read, Mary; Coccaro, Emil F

2015-12-01

Recent studies suggest that early life trauma is associated with elevations in circulating markers of inflammation in human subjects. History of aggression as a behavior, or aggression as a personality trait, is also associated with elevations of these inflammatory markers. Since early life trauma is associated with the development and maintenance of aggression in later life we examined the relationship of early life adversity, plasma inflammation markers (IL-6 and CRP) and oxidative stress markers (8-OH-DG and 8-ISO), and aggression in adult subjects with (n=79) and without (n=55) personality disorder. We used a series of mediated and moderated path models to test whether the effects of early adversity on later aggression may be mediated through markers of inflammation. Childhood abuse and parental control were associated with basal IL-6 and CRP concentrations. Path modeling suggested that childhood abuse was associated with aggression indirectly through CRP while parental control influenced aggression indirectly through IL-6 and CRP. Furthermore, these effects were independent of the effect of current depression. The results suggest that disruption of inflammatory processes represent one pathway by which early adversity influences aggression. Copyright © 2015 Elsevier B.V. All rights reserved.

The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia.

PubMed

Kale, Sachin; Yende, Sachin; Kong, Lan; Perkins, Amy; Kellum, John A; Newman, Anne B; Vallejo, Abbe N; Angus, Derek C

2010-11-04

To determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly. In an observational cohort of subjects with community-acquired pneumonia (CAP) recruited from emergency departments (ED) in 28 hospitals, we divided subjects into 5 age groups (<50, 51-64, 65-74, 75-84, and ≥85). We measured circulating levels of inflammatory (TNF, IL-6, and IL-10), hemostasis (D-dimer, Factor IX, thrombin-antithrombin complex, antithrombin and plasminogen-activator inhibitor-1), and cell-surface markers (TLR-2, TLR-4, and HLA-DR) during the first week of hospitalization and at discharge and compared 90-day mortality. We used logistic regression to compare odds ratios (OR) for 90-day mortality between age groups, adjusting for differences in pre-infection factors alone and then additionally adjusting for immune markers. Of 2,183 subjects, 495, 444, 403, 583, and 258 subjects were <50, 51-64, 65-74, 75-84, and ≥85 years of age, respectively. Large age-related differences were observed in 90-day mortality (0.82% vs. 3.2% vs. 6.4% vs. 12.8% vs. 13.6%, p<0.01). No age-related differences in inflammatory and cell surface markers occurred during the first week. Older subjects had higher pro-coagulant markers on ED presentation and over first week (p ≤ 0.03), but these differences were modest (1.0-1.7-fold differences). Odds of death for older adults changed minimally in models incorporating differences in hemostasis and inflammatory markers (for subjects ≥ 85 compared to those <50, OR = 4.36, when adjusted for pre-infection factors and OR = 3.49 when additionally adjusted for hemostasis markers). At discharge, despite clinical recovery as evidenced by normal vital signs in >85% subjects, older subjects had modestly increased hemostasis markers and IL-6 levels (p<0.01). Modest age-related increases in coagulation response occur during hospitalization for CAP; however these differences do not explain the large differences in mortality. Despite clinical recovery, immune resolution may be delayed in older adults at discharge.

CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor.

PubMed

Ronan, Nicola J; Einarsson, Gisli G; Twomey, Maria; Mooney, Denver; Mullane, David; NiChroinin, Muireann; O'Callaghan, Grace; Shanahan, Fergus; Murphy, Desmond M; O'Connor, Owen J; Shortt, Cathy A; Tunney, Michael M; Eustace, Joseph A; Maher, Michael M; Elborn, J Stuart; Plant, Barry J

2018-02-01

Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. Significant improvements in FEV 1 , BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Evidence in obese children: contribution of hyperlipidemia, obesity-inflammation, and insulin sensitivity.

PubMed

Chang, Chi-Jen; Jian, Deng-Yuan; Lin, Ming-Wei; Zhao, Jun-Zhi; Ho, Low-Tone; Juan, Chi-Chang

2015-01-01

Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children. We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits. Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%). Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.

Systemic and myocardial inflammatory response in coronary artery bypass graft surgery with miniaturized extracorporeal circulation: differences with a standard circuit and off-pump technique in a randomized clinical trial.

PubMed

Formica, Francesco; Mariani, Silvia; Broccolo, Francesco; Caruso, Rosa; Corti, Fabrizio; D'Alessandro, Stefano; Amigoni, Pietro; Sangalli, Fabio; Paolini, Giovanni

2013-01-01

Inflammatory response and hemodilution are the main drawbacks of extracorporeal circulation. We hypothesize that the use of miniaturized extracorporeal circulation (MECC) might lower the systemic and myocardial inflammatory patterns compared with a standard system (SECC) and off-pump coronary artery bypass grafting (OPCABG). Sixty-one patients undergoing isolated coronary artery bypass graft were prospectively randomized to MECC (n = 19), SECC (n = 20), or OPCABG (n = 22). Blood samples were collected from radial artery and coronary sinus to analyze blood lactate, hemodilution, and markers for inflammation and endothelial activation such as tumor necrosis factor (TNF)-α, interleukin-6, monocyte chemotactic protein-1, and E-selectin. No differences were observed in early clinical outcome. Interleukin -6 levels increased in every group during and after cardiac surgery, whereas TNF-α values grew in the SECC group (p = 0.05). E-selectin systemic values decreased during and after operation (p = 0.001) in every group. Monocyte chemotactic protein-1 systemic and cardiac levels raised only in SECC group (p = 0.014). In conclusion, MECC is comparable to SECC and OPCABG in the clinical outcome of low-risk patients, and it might be extensively used with no additional intraoperative risk. The analysis of the inflammatory patterns of endothelial activation shows MECC as effective as OPCABG, suggesting further studies to clarify MECC recommendation in high-risk patients.

Salivary Markers of Inflammation in Response to Acute Stress

PubMed Central

Slavish, Danica C.; Graham-Engeland, Jennifer E.; Smyth, Joshua M.; Engeland, Christopher G.

2014-01-01

There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1β, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1β, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research. PMID:25205395

A Double-Blinded Randomized Study Investigating a Possible Anti-Inflammatory Effect of Saxagliptin versus Placebo as Add-On Therapy in Patients with Both Type 2 Diabetes And Stable Coronary Artery Disease

PubMed Central

Åkra, Sissel; Weiss, Thomas W.; Øvstebø, Reidun; Aass, Hans Christian D.; Byrkjeland, Rune; Arnesen, Harald

2017-01-01

Background Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM. Methods Patients (n = 12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at −150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR). Results HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo (p = 0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group (p = 0.043, both), significantly different from that in the placebo (p = 0.009 and p = 0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers. Conclusion In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies. PMID:28596642

Supplementation with α-Lipoic Acid Alone or in Combination with Eicosapentaenoic Acid Modulates the Inflammatory Status of Healthy Overweight or Obese Women Consuming an Energy-Restricted Diet.

PubMed

Huerta, Ana E; Prieto-Hontoria, Pedro L; Sáinz, Neira; Martínez, J Alfredo; Moreno-Aliaga, María J

2016-03-09

The proinflammatory state induced by obesity plays an important role in obesity-related metabolic complications. Our objective was to evaluate whether dietary supplementation with α-lipoic acid (LA) and eicosapentaenoic acid (EPA), separately or in combination, could improve inflammatory and cardiovascular disease risk markers in healthy overweight or obese women consuming an energy-restricted diet. Within the context of the Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP) study, Caucasian women (n = 73) aged 20-50 y with a BMI (in kg/m 2 ) between 27.5 and 40 consumed an energy-restricted diet for 10 wk after being randomly assigned to 1 of 4 parallel experimental groups: a control group or groups supplemented with 1.3 g EPA/d, 0.3 g LA/d, or both. Secondary outcomes were measured at baseline and at the end of the study. These included circulating inflammatory [C-reactive protein (CRP), adiponectin, interleukin 6 (IL-6), chemerin, haptoglobin, amyloid A, and leukocytes] and cardiovascular disease risk markers (platelet count and circulating apelin, asymmetric dimethylarginine, vascular endothelial growth factor, and plasminogen activator inhibitor 1). Gene expression of IL6, adhesion G protein-coupled receptor E1 (ADGRE1), interleukin 10 (IL10), chemokine (C-C motif) ligand 2, and adiponectin was measured in subcutaneous abdominal adipose tissue biopsies at endpoint. Supplementation with LA caused a greater reduction in some circulating inflammatory risk markers, such as CRP (-0.13 ± 0.07 mg/dL compared with 0.06 ± 0.07 mg/dL, P < 0.05) and leukocyte count (-0.74 ± 0.18 × 10 3 /mm 3 compared with 0.06 ± 0.18 × 10 3 /mm 3 , P < 0.01), than in the groups that were not supplemented with LA. In contrast, the fall in apelin concentrations that accompanied weight loss was less pronounced in groups that were supplemented with LA (-1.1 ± 4.9 pg/mL) than in those that were not (-21.3 ± 4.8 pg/mL, P < 0.01). In adipose tissue, compared with those who did not receive EPA, EPA-supplemented groups exhibited a downregulation of ADGRE1 (0.7 ± 0.1-fold compared with 1.0 ± 0.1-fold) (P < 0.05) and an upregulation of IL10 (1.8 ± 0.2-fold compared with 1.0 ± 0.2-fold) (P < 0.05) gene expression. Dietary supplementation with LA improves some systemic inflammatory and cardiovascular disease-related risk markers in healthy overweight or obese women independently of weight loss, whereas EPA modulates inflammation-related genes in adipose tissue. This trial was registered at clinicaltrials.gov as NCT01138774. © 2016 American Society for Nutrition.

Systemic inflammatory response following acute myocardial infarction

PubMed Central

Fang, Lu; Moore, Xiao-Lei; Dart, Anthony M; Wang, Le-Min

2015-01-01

Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial infarction, and heart failure) in patients with AMI. PMID:26089856

Impairment of Circulating CD4⁺CD25⁺GARP⁺ regulatory T cells in patients with acute coronary syndrome.

PubMed

Meng, Kai; Zhang, Wei; Zhong, Yucheng; Mao, Xiaobo; Lin, Yingzhong; Huang, Ying; Lang, Mingjian; Peng, Yudong; Zhu, Zhengfeng; Liu, Yuzhou; Zhao, Xiaoqi; Yu, Kunwu; Wu, Bangwei; Ji, Qingwei; Zeng, Qiutang

2014-01-01

Atherosclerosis (AS) is an inflammatory and immune disease. Regulatory T cells (Tregs) suppress the activation of T cells and have been shown to play a protective role during the pathogenesis of AS. However, specific markers for Tregs are lacking. Recently, glycoprotein A repetitions predominant (GARP) was discovered as a specific marker of activated Tregs, and we therefore utilized GARP as a specific surface marker for Tregs in the current study. To assess whether GARP(+) Tregs are downregulated in patients with acute coronary syndrome (ACS), we examined CD4(+)CD25(+)GARP(+) T cell frequencies as well as their associated cytokines and suppressive function. Additionally, we compared GARP expression to that of FOXP3, which may be more sensitive as a marker of activated Tregs in patients with ACS. Patients with ACS demonstrated a significant decrease in circulating CD4(+)CD25(+)GARP(+) Tregs. Moreover, the suppressive function of Tregs and levels of related cytokines were also impaired in ACS patients compared to those with stable angina (SA) or normal coronary artery (NCA). Additionally, after TCR stimulation, peripheral blood mononuclear cells (PBMCs) from patients with ACS exhibited a decrease in CD4(+)CD25(+)GARP(+) Tregs. These fnding indicate that circulating CD4(+)CD25(+)GARP(+) Tregs are impaired in patients withACS. Thus, targeting GARP may promote the protective function of Tregs in ACS. © 2014 S. Karger AG, Basel.

Organisational justice and markers of inflammation: the Whitehall II study.

PubMed

Elovainio, Marko; Ferrie, Jane E; Singh-Manoux, Archana; Gimeno, David; De Vogli, Roberto; Shipley, Martin; Vahtera, Jussi; Brunner, Eric; Marmot, Michael G; Kivimäki, Mika

2010-02-01

Low organisational justice has been shown to be associated with increased risk of various health problems, but the underlying mechanisms remain unclear. We tested whether organisational injustice contributes to chronic inflammation in a population of middle-aged men and women. This prospective cohort study uses data from 3205 men and 1204 women aged 35-55 years at entry into the Whitehall II study (phase 1, 1985-1988). Organisational justice perceptions were assessed at phase 1 and phase 2 (1989-1990) and circulating inflammatory markers C-reactive protein (CRP) and interleukin (IL)-6 at phase 3 (1991-1993) and phase 7 (2003-2004). In men, low organisational justice was associated with increased CRP levels at both follow-ups (phase 3 and 7) and increased IL-6 at the second follow-up (phase 7). The long term (phase 7) associations were largely independent of covariates, such as age, employment grade, body mass index and depressive symptoms. In women, no relationship was found between organisational justice and CRP or IL-6. This study suggests that organisational injustice is associated with increased long-term levels of inflammatory markers among men.

Inflammatory biomarkers for persistent fatigue in breast cancer survivors.

PubMed

Collado-Hidalgo, Alicia; Bower, Julienne E; Ganz, Patricia A; Cole, Steve W; Irwin, Michael R

2006-05-01

This study seeks to define immunologic and inflammatory variables associated with persistent post-treatment fatigue in breast cancer survivors. Leukocyte subsets, plasma inflammatory markers, and ex vivo proinflammatory cytokine production were assessed in 50 fatigued and nonfatigued breast cancer survivors recruited > or = 2 years after successful primary therapy. Multivariate statistical analyses were used to define a composite immunologic biomarker of fatigue risk. Fatigued breast cancer survivors were distinguished from nonfatigued survivors by increased ex vivo monocyte production of interleukin (IL)-6 and tumor necrosis factor-alpha following lipopolysaccharide stimulation, elevated plasma IL-1ra and soluble IL-6 receptor (sIL-6R/CD126), decreased monocyte cell-surface IL-6R, and decreased frequencies of activated T lymphocytes and myeloid dendritic cells in peripheral blood (all P < 0.05). An inverse correlation between sIL-6R and cell-surface IL-6R was consistent with inflammation-mediated shedding of IL-6R, and in vitro studies confirmed that proinflammatory cytokines induced such shedding. Multivariate linear discriminant function analysis identified two immunologic markers, the ratio of sIL-6R to monocyte-associated IL-6R and decreased circulating CD69+ T lymphocytes, as highly diagnostic of fatigue (P = 0.0005), with cross-validation estimates indicating 87% classification accuracy (sensitivity = 0.83; specificity = 0.83). These results extend links between fatigue and inflammatory markers to show a functional alteration in proinflammatory cytokine response to lipopolysaccharide and define a prognostic biomarker of behavioral fatigue.

Consumption of protein-enriched milk has minor effects on inflammation in older adults-A 12-week double-blind randomized controlled trial.

PubMed

Gjevestad, Gyrd O; Ottestad, Inger; Biong, Anne Sofie; Iversen, Per Ole; Retterstøl, Kjetil; Raastad, Truls; Skålhegg, Bjørn S; Ulven, Stine M; Holven, Kirsten B

2017-03-01

Aging is associated with increased levels of circulating inflammatory markers and reduced muscle mass and strength. We investigated whether intake of protein-enriched milk for 12 weeks would influence markers of inflammation among adults ≥70years of age with reduced physical strength. In a double-blind randomized controlled intervention study, subjects were randomly allocated into two groups, receiving a protein-enriched milk (2×20g protein/d, n=14, mean (±SD) age 76.9±4.9 yrs) or an isocaloric carbohydrate drink (n=17, age 77.7±4.8 yrs) for 12 weeks. We measured serum and mRNA expression levels of inflammatory markers in PBMCs. Significant differences in the mRNA expression of nuclear receptor subfamily, group H, member 3 (NR1H3, encoding the LXRα transcription factor) and interferon gamma (INFG) were observed between groups. The mRNA level of TNFRSF1A was significantly reduced, while the mRNA level of dipeptidyl-peptidase 4 (DPP4) was significantly increased, in the control group. The serum level of TNFα increased significantly in the control group, while sTNFRSF1A increased significantly in both groups, but with no significant differences between groups. Consumption of a low-fat, protein-enriched milk for 12 weeks had minor effects on inflammatory related markers in older adults compared to an isocaloric carbohydrate drink. Copyright © 2017 Elsevier B.V. All rights reserved.

The Hypothalamic Inflammatory/Gliosis Response to Neonatal Overnutrition Is Sex and Age Dependent.

PubMed

Argente-Arizón, Pilar; Díaz, Francisca; Ros, Purificación; Barrios, Vicente; Tena-Sempere, Manuel; García-Segura, Luis Miguel; Argente, Jesús; Chowen, Julie A

2018-01-01

Astrocytes participate in both physiological and pathophysiological responses to metabolic and nutrient signals. Although most studies have focused on the astrocytic response to weight gain due to high-fat/high-carbohydrate intake, surplus intake of a balanced diet also induces excess weight gain. We have accessed the effects of neonatal overnutrition, which has both age- and sex-dependent effects on weight gain, on hypothalamic inflammation/gliosis. Although both male and female Wistar rats accumulate excessive fat mass as early as postnatal day (PND) 10 with neonatal overnutrition, no increase in hypothalamic cytokine levels, markers of astrocytes or microglia, or inflammatory signaling pathways were observed. At PND 50, no effect of neonatal overnutriton was found in either sex, whereas at PND 150, males again weighed significantly more than their controls, and this was coincident with an increase in markers of inflammation and astrogliosis in the hypothalamus. Circulating triglycerides and free fatty acids were also elevated in these males, but not in females or in either sex at PND 10. Thus, the effects of fatty acids and estrogens on astrocytes in vitro were analyzed. Our results indicate that changes in circulating fatty acid levels may be involved in the induction of hypothalamic inflammation/gliosis in excess weight gain, even on a normal diet, and that estrogens could participate in the protection of females from these processes. In conclusion, the interaction of developmental influences, dietary composition, age, and sex determines the central inflammatory response and the associated long-term outcomes of excess weight gain. Copyright © 2018 Endocrine Society.

Leptin Resistance: A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease

PubMed Central

Martin, Seth S.; Qasim, Atif; Reilly, Muredach P.

2015-01-01

Nonstructured Abstract Leptin is an adipocyte-derived hormone and cytokine that regulates energy balance through a wide range of functions, including several important to cardiovascular health. Increased circulating leptin, a marker of leptin resistance, is common in obesity and independently associated with insulin resistance and cardiovascular disease (CVD) in humans. Mechanisms of leptin resistance include genetic mutation, leptin self regulation, limited tissue access and cellular or circulating molecular regulation. Evidence suggests that central leptin resistance causes obesity and that obesity-induced leptin resistance injures numerous peripheral tissues, including liver, pancreas, platelets, vasculature, and myocardium. This metabolic- and inflammatory-mediated injury may result from either resistance to leptin’s action in selective tissues, or excess leptin action from adiposity associated hyperleptinemia. In this sense, the term “leptin resistance” encompasses a complex pathophysiological phenomenon. The leptin axis has functional interactions with elements of metabolism, such as insulin, and inflammation, including mediators of innate immunity such as interleukin-6. Leptin is even purported to physically interact with C-reactive protein (CRP), resulting in leptin resistance, which is particularly intriguing given CRP’s well-studied relationship to CVD. Given that plasma levels of leptin and inflammatory markers are correlated and also predict cardiovascular risk, it is conceivable that part of this risk may be mediated through leptin-resistance related insulin resistance, chronic inflammation, type II diabetes, hypertension, atherothrombosis and myocardial injury. Leptin resistance and its interactions with metabolic and inflammatory factors, therefore, represent potential novel diagnostic and therapeutic targets in obesity-related cardiovascular disease. PMID:18926322

Effects of fish and krill oil on gene expression in peripheral blood mononuclear cells and circulating markers of inflammation: a randomised controlled trial.

PubMed

Rundblad, Amanda; Holven, Kirsten B; Bruheim, Inge; Myhrstad, Mari C; Ulven, Stine M

2018-01-01

Marine n -3 (omega-3) fatty acids alter gene expression by regulating the activity of transcription factors. Krill oil is a source of marine n -3 fatty acids that has been shown to modulate gene expression in animal studies; however, the effect in humans is not known. Hence, we aimed to compare the effect of intake of krill oil, lean and fatty fish with a similar content of n -3 fatty acids, and high-oleic sunflower oil (HOSO) with added astaxanthin on the expression of genes involved in glucose and lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC) as well as circulating inflammatory markers. In an 8-week trial, healthy men and women aged 18-70 years with fasting TAG of 1·3-4·0 mmol/l were randomised to receive krill oil capsules ( n 12), HOSO capsules ( n 12) or lean and fatty fish ( n 12). The weekly intakes of marine n -3 fatty acids from the interventions were 4654, 0 and 4103 mg, respectively. The mRNA expression of four genes, PPAR γ coactivator 1A ( PPARGC1A ), steaoryl-CoA desaturase ( SCD ), ATP binding cassette A1 ( ABCA1 ) and cluster of differentiation 40 ( CD40 ), were differently altered by the interventions. Furthermore, within-group analyses revealed that krill oil down-regulated the mRNA expression of thirteen genes, including genes involved in glucose and cholesterol metabolism and β-oxidation. Fish altered the mRNA expression of four genes and HOSO down-regulated sixteen genes, including several inflammation-related genes. There were no differences between the groups in circulating inflammatory markers after the intervention. In conclusion, the intake of krill oil and HOSO with added astaxanthin alter the PBMC mRNA expression of more genes than the intake of fish.

Targeting B cells in immune-mediated inflammatory disease: a comprehensive review of mechanisms of action and identification of biomarkers.

PubMed

Dörner, Thomas; Kinnman, Nils; Tak, Paul P

2010-03-01

B cell-depletion therapy, particularly using anti-CD20 treatment, has provided proof of concept that targeting B cells and the humoral response may result in clinical improvements in immune-mediated inflammatory disease. In this review, the mechanisms of action of B cell-targeting drugs are investigated, and potential biomarkers associated with response to treatment in patients with autoimmune diseases are identified. Most available data relate to B cell depletion using anti-CD20 therapy (rituximab) in patients with rheumatoid arthritis (RA). Treatment leads to significant clinical benefit, but apparently fails to deplete long-lived plasma cells, and discontinuation is associated with relapse. Biomarkers commonly used in studies of B cell-targeted therapies include rheumatoid factor, anti-citrullinated peptide antibodies, and immunoglobulin (Ig) levels. More recently, there has been interest in markers such as B cell phenotype analysis, and B lymphocyte stimulator (BLyS)/a proliferation-inducing ligand (APRIL), the latter particularly in studies of the IgG Fc-transmembrane activator and CAML interactor (TACI) fusion protein (atacicept) and anti-BLyS therapy (belimumab). Data from clinical trials of B cell-depleting agents in RA suggest that specific autoantibodies, BLyS, APRIL, and circulating and synovial B lineage cell levels may have potential as biomarkers predictive of response to treatment. Further trials validating these markers against clinical outcomes in RA are required. In patients with systemic lupus erythematosus, Fc receptors and levels of circulating immune cells (including B cells and natural killer cells) may be relevant markers. 2010 Elsevier Inc. All rights reserved.

Coxiella burnetii Induces Inflammatory Interferon-Like Signature in Plasmacytoid Dendritic Cells: A New Feature of Immune Response in Q Fever

PubMed Central

Ka, Mignane B.; Mezouar, Soraya; Ben Amara, Amira; Raoult, Didier; Ghigo, Eric; Olive, Daniel; Mege, Jean-Louis

2016-01-01

Plasmacytoid dendritic cells (pDCs) play a major role in antiviral immunity via the production of type I interferons (IFNs). There is some evidence that pDCs interact with bacteria but it is not yet clear whether they are protective or contribute to bacterial pathogenicity. We wished to investigate whether Coxiella burnetii, the agent of Q fever, interacts with pDCs. The stimulation of pDCs with C. burnetii increased the expression of activation and migratory markers (CD86 and CCR7) as determined by flow cytometry and modulated gene expression program as revealed by a microarray approach. Indeed, genes encoding for pro-inflammatory cytokines, chemokines, and type I INF were up-regulated. The up-regulation of type I IFN was correlated with an increase in IFN-α release by C. burnetii-stimulated pDCs. We also investigated pDCs in patients with Q fever endocarditis. Using flow cytometry and a specific gating strategy, we found that the number of circulating pDCs was significantly lower in patients with Q fever endocarditis as compared to healthy donors. In addition, the remaining circulating pDCs expressed activation and migratory markers. As a whole, our study identified non-previously reported activation of pDCs by C. burnetii and their modulation during Q fever. PMID:27446817

Inflammatory markers in relation to long-term air pollution.

PubMed

Mostafavi, Nahid; Vlaanderen, Jelle; Chadeau-Hyam, Marc; Beelen, Rob; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard; Kyrtopoulos, Soterios Α; Vermeulen, Roel

2015-08-01

Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65 μg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2 μg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Yoga and immune system functioning: a systematic review of randomized controlled trials.

PubMed

Falkenberg, R I; Eising, C; Peters, M L

2018-02-10

Yoga is an ancient mind-body practice that is increasingly recognized to have health benefits in a variety of clinical and non-clinical conditions. This systematic review summarizes the findings of randomized controlled trials examining the effects of yoga on immune system functioning which is imperative to justify its application in the clinic. Fifteen RCTs were eligible for the review. Even though the existing evidence is not entirely consistent, a general pattern emerged suggesting that yoga can downregulate pro-inflammatory markers. In particular, the qualitative evaluation of RCTs revealed decreases in IL-1beta, as well as indications for reductions in IL-6 and TNF-alpha. These results imply that yoga may be implemented as a complementary intervention for populations at risk or already suffering from diseases with an inflammatory component. Beyond this, yoga practice may exert further beneficial effects by enhancing cell-mediated and mucosal immunity. It is hypothesized that longer time spans of yoga practice are required to achieve consistent effects especially on circulating inflammatory markers. Overall, this field of investigation is still young, hence the current body of evidence is small and for most immune parameters, more research is required to draw distinct conclusions.

Efficacy of Metreleptin in Obese Patients With Type 2 Diabetes: Cellular and Molecular Pathways Underlying Leptin Tolerance

PubMed Central

Moon, Hyun-Seuk; Matarese, Giuseppe; Brennan, Aoife M.; Chamberland, John P.; Liu, Xiaowen; Fiorenza, Christina G.; Mylvaganam, Geetha H.; Abanni, Luisa; Carbone, Fortunata; Williams, Catherine J.; De Paoli, Alex M.; Schneider, Benjamin E.; Mantzoros, Christos S.

2011-01-01

OBJECTIVE Metreleptin has been efficacious in improving metabolic control in patients with lipodystrophy, but its efficacy has not been tested in obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We studied the role of leptin in regulating the endocrine adaptation to long-term caloric deprivation and weight loss in obese diabetic subjects over 16 weeks in the context of a double-blinded, placebo–controlled, randomized trial. We then performed detailed interventional and mechanistic signaling studies in humans in vivo, ex vivo, and in vitro. RESULTS In obese patients with diabetes, metreleptin administration for 16 weeks did not alter body weight or circulating inflammatory markers but reduced HbA1c marginally (8.01 ± 0.93–7.96 ± 1.12, P = 0.03). Total leptin, leptin-binding protein, and antileptin antibody levels increased, limiting free leptin availability and resulting in circulating free leptin levels of ∼50 ng/mL. Consistent with clinical observations, all metreleptin signaling pathways studied in human adipose tissue and peripheral blood mononuclear cells were saturable at ∼50 ng/mL, with no major differences in timing or magnitude of leptin-activated STAT3 phosphorylation in tissues from male versus female or obese versus lean humans in vivo, ex vivo, or in vitro. We also observed for the first time that endoplasmic reticulum (ER) stress in human primary adipocytes inhibits leptin signaling. CONCLUSIONS In obese patients with diabetes, metreleptin administration did not alter body weight or circulating inflammatory markers but reduced HbA1c marginally. ER stress and the saturable nature of leptin signaling pathways play a key role in the development of leptin tolerance in obese patients with diabetes. PMID:21617185

Resveratrol supplementation decreases blood glucose without changing the circulating CD14+CD16+ monocytes and inflammatory cytokines in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.

PubMed

Khodabandehloo, Hadi; Seyyedebrahimi, ShadiSadat; Esfahani, Ensieh Nasli; Razi, Farideh; Meshkani, Reza

2018-06-01

Chronic low-grade inflammation is the hallmark of type 2 diabetes (T2D). Although in vitro and animal studies have shown that resveratrol exerts anti-inflammatory effects, clinical trials addressing these effects in patients with T2D are limited. Therefore, in the present study, we hypothesized that supplementation of resveratrol might improve inflammatory markers in patients with T2D in a randomized, double-blind, placebo-controlled clinical trial. A total of 45 T2D patients were supplemented with either of 800 mg/d resveratrol or placebo capsules for 8 weeks. Percentage of CD14 + CD16 + monocytes, plasma levels of inflammatory cytokines (tumor necrosis factor α, interleukin [IL] 1β, IL-6, and monocyte chemoattractant protein-1), the expression levels of genes involved in the inflammatory responses (toll-like receptor 2, toll-like receptor 4, and nuclear factor κB), lipopolysaccharide-stimulated cytokine (tumor necrosis factor α, IL-1β, and IL-6) secretion from peripheral blood mononuclear cells, and metabolic and anthropometric parameters were assessed at both the baseline level and the end of the study. Compared with the placebo group, we could not detect any significant difference in the percentage of CD14 + CD16 + monocytes, lipopolysaccharide-induced cytokine secretion, plasma levels of inflammatory cytokines, and the expression of inflammatory genes in resveratrol group. Moreover, we did not find any significant change in the metabolic and anthropometric parameters except for a significant reduction in fasting blood glucose and blood pressure. In conclusion, 8-week supplementation of resveratrol reduces blood glucose level in patients with T2D without improving their inflammatory markers. Copyright © 2018 Elsevier Inc. All rights reserved.

Mesenchymal-Epithelial Transition and Circulating Tumor Cells in Small Cell Lung Cancer.

PubMed

Hamilton, Gerhard; Rath, Barbara

2017-01-01

Cancer patients die of metastatic disease but knowledge regarding individual steps of this complex process of intravasation, spread and extravasation leading to secondary lesions is incomplete. Subpopulations of tumor cells are supposed to undergo an epithelial-mesenchymal transition (EMT), to enter the bloodstream and eventually establish metastases in a reverse process termed mesenchymal-epithelial transition (MET). Small cell lung cancer (SCLC) represents a unique model to study metastatic spread due to early dissemination and relapse, as well as availability of a panel of circulating cancer cell (CTC) lines recently. Additionally, chemosensitive SCLC tumor cells switch to a completely resistant phenotype during cancer recurrence. In advanced disease, SCLC patients display extremely high blood counts of CTCs in contrast to other tumors, like breast, prostate and colon cancer. Local inflammatory conditions at the primary tumor site and recruitment of macrophages seem to increase the shedding of tumor cells into the circulation in processes which may proceed independently of EMT. Since millions of cells are released by tumors into the circulation per day, analysis of a limited number of CTCs at specific time points are difficult to be related to the development of metastatic lesions which may occur approximately one year later. We have obtained a panel of SCLC CTC cell line from patients with relapsing disease, which share characteristic markers of this malignancy and a primarily epithelial phenotype with unique formation of large tumorospheres, containing quiescent and hypoxic cells. Although smoking and inflammation promote EMT, partial expression of vimentin indicates a transitional state with partial EMT in these cell lines at most. The CTC lines exhibit high expression of EpCAM , absent phosphorylation of β-catenin and background levels of Snail. Provided that these tumor cells had ever undergone EMT, here in advanced disease MET seem to have occurred already in the peripheral circulation. Alternative explanations for the expression of mesenchymal markers of the CTC lines are the heterogeneity of SCLC cells, cooperative migration or altered gene expression in response to the inflammatory tumor microenvironment allowing for tumor spread without EMT/MET.

Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness.

PubMed

Mikacenic, Carmen; Hahn, William O; Price, Brenda L; Harju-Baker, Susanna; Katz, Ronit; Kain, Kevin C; Himmelfarb, Jonathan; Liles, W Conrad; Wurfel, Mark M

2015-01-01

Endothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS. We studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers. Higher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes. In critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.

Psychophysiological Correlates of Systemic Inflammation in Black and White Men

PubMed Central

Lockwood, Kimberly G.; Jennings, J. Richard; Matthews, Karen A.

2016-01-01

Inflammation plays a critical role in the pathophysiology of cardiovascular disease (CVD) and levels of circulating inflammatory markers are associated with future CVD risk. However, the physiological mechanisms that control systemic levels of circulating inflammatory markers are not well understood. Here, we explore possible autonomic nervous system mechanisms by testing whether resting and stressor-evoked cardiovascular responses are associated with two markers of systemic inflammation: interleukin(IL)-6 and C-reactive protein (CRP). Subjects were 159 Black and 129 White men (M = 33.0 years) who completed a laboratory protocol including an anger recall speech task. Electrocardiography and impedance cardiography data were collected during a resting baseline, the speech task, and a final recovery period. Hierarchical regressions tested whether resting or stressor-evoked levels of heart rate (HR), high-frequency heart rate variability (HF-HRV), pre-ejection period (PEP), and pulse transit time (PTT) were associated with CRP or IL-6. Higher resting HR was associated with higher CRP (β = .19, p = .003) and IL-6 (β = .13, p < .05). Similarly, shorter resting PTT was associated with higher CRP (β = −.21, p < .001) and IL-6 (β = −.14, p = .02). In addition, greater stressor-evoked decreases in HF-HRV were associated with higher CRP (β = −.14, p = .01). Associations were independent of age, race, body mass index (BMI), smoking behavior, and socioeconomic status. Resting HF-HRV and PEP were also associated with CRP and IL-6, but associations were not significant after controlling for BMI and smoking behavior. These findings indicate that resting HR and PTT, as well stressor-evoked HF-HRV reactivity, are associated with systemic inflammation. Our results suggest that both tonic and stressor-evoked sympathetic and parasympathetic nervous system activity may contribute to regulation of systemic inflammation. PMID:27568363

Innate immunity, insulin resistance and type 2 diabetes.

PubMed

Fernández-Real, José Manuel; Pickup, John C

2008-01-01

Recent evidence has disclosed previously unrecognized links among insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to altered production or function of circulating innate immune proteins, cellular pattern-recognition receptors and inflammatory cytokines have been linked with insulin resistance, type 2 diabetes, obesity and atherosclerosis. Cellular innate immune associations with obesity and insulin resistance include increased white blood cell count and adipose tissue macrophage numbers. The innate immune response is modulated possibly by both predisposition (genetic or fetal programming), perhaps owing to evolutionary pressures caused by acute infections at the population level (pandemics), and chronic low exposure to environmental products or infectious agents. The common characteristics shared among innate immunity activation, obesity and insulin resistance are summarized.

Inflammatory and bone turnover markers in relation to PTH and vitamin D status among saudi postmenopausal women with and without osteoporosis

PubMed Central

Al-Daghri, Nasser M; Yakout, Sobhy; Al-Shehri, Eman; Al-Fawaz, Hanan A; Aljohani, Naji; Al-Saleh, Yousef

2014-01-01

Postmenopausal osteoporosis is characterized by rapid bone loss occurring in the post-menopausal period. The bone loss predominantly involves the trabecular bone and is brought about by an imbalance between the bone remodeling process which can be influenced by factors that could cause or contribute to osteoporosis. Pro-inflammatory cytokines (Il-1β, Il-6, IL-8 and TNF-α) have been implicated in the regulation of bone cells and play a critical role in bone remodeling. They act both directly and indirectly to increase bone resorption, and/or inhibit bone formation. The aim of the study is to determine whether pro-inflammatory cytokines correlate with bone turnover markers (BTM) in a cohort of Saudi post-menopausal women with or without osteoporosis and which BTMs will correlate with PTH and Vitamin D for use in osteoporosis diagnosis. The study is composed of 100 post-menopausal patients and 100 controls aged around 50 years. Serum concentrations of pro-inflammatory and BTMs as well as PTH and vitamin D were determined by ELISA, Luminex and electrochemiluminescence. Serum calcium, phosphorus, glucose, and lipid profile were measured by using a chemical analyzer. There was a significant increase in the levels of pro-inflammatory cytokines, PTH, CTx, and glucose. A significantly lower vitamin D and osteocalcin levels were observed in subjects with osteoporosis than those without. No significant differences were recorded in the circulating lipid profile between groups. The present study proved that the pro-inflammatory cytokines accelerate the bone loss in postmenopausal women. PMID:25419393

Inflammatory and bone turnover markers in relation to PTH and vitamin D status among Saudi postmenopausal women with and without osteoporosis

PubMed Central

Al-Daghri, Nasser M; Yakout, Sobhy; Al-Shehri, Eman; Al-Fawaz, Hanan; Aljohani, Naji; Al-Saleh, Yousef

2014-01-01

Postmenopausal osteoporosis is characterized by rapid bone loss occurring in the post-menopausal period. The bone loss predominantly involves the trabecular bone and is brought about by an imbalance between the bone remodeling process which can be influenced by factors that could cause or contribute to osteoporosis. Pro-inflammatory cytokines (Il-1β, Il-6, IL-8 and TNF-α) have been implicated in the regulation of bone cells and play a critical role in bone remodeling. They act both directly and indirectly to increase bone resorption, and/or inhibit bone formation. The aim of the study is to determine whether pro-inflammatory cytokines correlate with bone turnover markers (BTM) in a cohort of Saudi post-menopausal women with or without osteoporosis and which BTMs will correlate with PTH and Vitamin D for use in osteoporosis diagnosis. The study is composed of 100 post-menopausal patients and 100 controls aged 50 years and above. Serum concentrations of pro-inflammatory and BTMs as well as PTH and vitamin D were determined by ELISA, Luminex and electrochemiluminescence. Serum calcium, phosphorus, glucose, and lipid profile were measured by using a chemical analyzer. There was a significant increase in the levels of pro-inflammatory cytokines, PTH, CTx, and glucose. A significantly lower vitamin D and osteocalcin levels were observed in subjects with osteoporosis than those without. No significant differences were recorded in the circulating lipid profile between groups. The present study proved that the pro-inflammatory cytokines accelerate the bone loss in postmenopausal women. PMID:25356143

A Preliminary Study of the Effects of Repeated Massage on Hypothalamic–Pituitary–Adrenal and Immune Function in Healthy Individuals: A Study of Mechanisms of Action and Dosage

PubMed Central

Schettler, Pamela; Bresee, Catherine

2012-01-01

Abstract Objectives This study gathers preliminary data about the biologic effects of repeated Swedish massage therapy compared to a light-touch control condition. Design The study design was a 5-week comparison of repeated Swedish massage and light touch on oxytocin (OT), arginine-vasopressin (AVP), adrenal corticotropin hormone (ACTH), cortisol (CORT), circulating phenotypic lymphocyte markers, and mitogen-stimulated cytokine function. Setting The setting was an outpatient research unit in an academic medical center. Participants The study subjects were medically and psychiatrically healthy young adults. Intervention The study comprised 45 minutes of Swedish massage or light touch, using highly specified and identical protocols, either weekly or twice weekly for 5 weeks. Outcome measures The outcome measures were mean differences between massage and light touch on OT, AVP, ACTH, CORT, lymphocyte markers, and cytokine levels. Results Compared to the touch control condition, weekly Swedish massage stimulated a sustained pattern of increased circulating phenotypic lymphocyte markers and decreased mitogen-stimulated cytokine production, similar to what was previously reported for a single massage session, while having minimal effect on hypothalamic–pituitary–adrenal function. Twice-weekly massage produced a different response pattern with increased OT levels, decreased AVP, and decreased CORT but little effect on circulating lymphocyte phenotypic markers and a slight increase in mitogen-stimulated interferon-γ, tumor necrosis factor-α, interleukin (IL)-1b and IL-2 levels, suggesting increased production of pro-inflammatory cytokines. Conclusions There are sustained cumulative biologic actions for the massage and touch interventions that persist for several days or a week, and these differ profoundly depending on the dosage (frequency) of sessions. Confirmatory studies in larger samples are needed. PMID:22775448

Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals.

PubMed

Luthold, Renata V; Fernandes, Gabriel R; Franco-de-Moraes, Ana Carolina; Folchetti, Luciana G D; Ferreira, Sandra Roberta G

2017-04-01

Due to immunomodulatory properties, vitamin D status has been implicated in several diseases beyond the skeletal disorders. There is evidence that its deficiency deteriorates the gut barrier favoring translocation of endotoxins into the circulation and systemic inflammation. Few studies investigated whether the relationship between vitamin D status and metabolic disorders would be mediated by the gut microbiota composition. We examined the association between vitamin D intake and circulating levels of 25(OH)D with gut microbiota composition, inflammatory markers and biochemical profile in healthy individuals. In this cross-sectional analysis, 150 young healthy adults were stratified into tertiles of intake and concentrations of vitamin D and their clinical and inflammatory profiles were compared. The DESeq2 was used for comparisons of microbiota composition and the log2 fold changes (log2FC) represented the comparison against the reference level. The association between 25(OH)D and fecal microbiota (16S rRNA sequencing, V4 region) was tested by multiple linear regression. Vitamin D intake was associated with its concentration (r=0.220, p=0.008). There were no significant differences in clinical and inflammatory variables across tertiles of intake. However, lipopolysaccharides increased with the reduction of 25(OH)D (p-trend <0.05). Prevotella was more abundant (log2FC 1.67, p<0.01), while Haemophilus and Veillonella were less abundant (log2FC -2.92 and -1.46, p<0.01, respectively) in the subset with the highest vitamin D intake (reference) than that observed in the other subset (first plus second tertiles). PCR (r=-0.170, p=0.039), E-selectin (r=-0.220, p=0.007) and abundances of Coprococcus (r=-0.215, p=0.008) and Bifdobacterium (r=-0.269, p=0.001) were inversely correlated with 25(OH)D. After adjusting for age, sex, season and BMI, 25(OH)D maintained inversely associated with Coprococcus (β=-9.414, p=0.045) and Bifdobacterium (β=-1.881, p=0.051), but significance disappeared following the addition of inflammatory markers in the regression models. The role of vitamin D in the maintenance of immune homeostasis seems to occur in part by interacting with the gut microbiota. The attenuation of association of bacterial genera by inflammatory markers suggests that inflammation participate in part in the relationship between the gut microbiota and vitamin D concentration. Studies with appropriate design are necessary to address hypothesis raised in the current study. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in circulating cytokines and markers of muscle damage in elite cyclists during a multi-stage competition.

PubMed

Córdova Martínez, Alfredo; Martorell Pons, Miquel; Sureda Gomila, Antoni; Tur Marí, Josep A; Pons Biescas, Antoni

2015-09-01

The purpose of this study was to determine the changes in the basal and post-exercise plasma markers of muscular damage, lipid peroxidation and cytokines in eight male well-trained semiprofessional cyclists, in response to a three consecutive-day cycling competition. Serum markers of oxidative and muscular damage - creatine kinase activity, lactate dehydrogenase activity, myoglobin and malondialdehyde (MDA), creatinine and nitrite levels - followed a sawtooth-type representation throughout the competition. MDA showed an accumulative pattern, evidenced in the post-race values of the third stage which were significantly higher with respect to the values of the first stage. Cortisol levels were significantly influenced by an interaction between the exercise and the stage factors, with higher values on the 4th day. Plasma cytokine levels were only determined before the first stage and post-race, after the third stage. The exercise increased TNFα, IL6, IL2 and IFNγ levels, whereas IL1β was unchanged. In conclusion, cyclist stages induced oxidative and cellular muscle damage which is partially recovered to basal values by the next morning. Repetitive stages during the cycling competition accumulated plasma muscular damage and lipid peroxidation markers and pro-inflammatory cytokines, probably as a result of local inflammatory responses. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Interleukin10-1082 A/G polymorphism: Allele frequency, correlation with disease markers, messenger RNA and serum levels in North Indian rheumatoid arthritis patients.

PubMed

Jahid, Mohd; Rehan-Ul-Haq; Avasthi, Rajnish; Ahmed, Rafat Sultana

2018-05-01

Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder of unknown etiology. IL-10 stimulates B cell survival and is involved in antibody isotype switching. The serum IL-10 levels are increased in RA patients. Ethnicity influences polymorphisms in cytokine genes. Therefore, this study was designed to explore possible association, if any, between polymorphism of IL10-1082 A/G, serum cytokine levels, inflammatory markers and gene expression in RA patients of North India. A total of 187 RA patients classified according to American college of rheumatology 2010 criteria and 214 controls were included in the study. Levels of serum IL-10 and inflammatory markers were estimated by ELISA. PCR-RFLP was used to analyze IL10-1082 A/G polymorphism. Quantitative real time PCR was used to measure the mRNA expression of IL-10 gene. The serum inflammatory markers were significantly higher in RA patients. Circulating IL-10 levels were positively and significantly correlated with RF (r = 0.28), anti-CCP (r = 0.26), CRP (r = 0.17) and mRNA expression levels (r = 0.59) among RA patients. Homozygous mutant variant (GG) and heterozygous mutant variant (AG) were associated with patients of RA (OR = 2.87 and 1.55, p < 0.05) as compared to controls. The association still persisted when the heterozygous and homozygous mutants (AG + GG) were clubbed together (OR = 1.67, p < 0.05). The mRNA expression of IL-10 was found to be 3.63 folds higher (housekeeping gene, β-actin) and 2.42 folds higher (housekeeping gene, 18S rRNA) in RA patients as compared to controls. The results indicate that IL10-1082 A/G polymorphism is associated with genetic susceptibility/predisposition to RA in North Indian population. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Omega-3 fatty acids, inflammatory status and biochemical markers of patients with systemic lupus erythematosus: a pilot study.

PubMed

Curado Borges, Mariane; de Miranda Moura Dos Santos, Fabiana; Weiss Telles, Rosa; Melo de Andrade, Marcus Vinícius; Toulson Davisson Correia, Maria Isabel; Lanna, Cristina Costa Duarte

Studies have shown that omega-3 fatty acids reduce the concentrations of eicosanoids, cytokines, chemokines, C-reactive protein (CRP) and other inflammatory mediators. To investigate the effects of omega-3 fatty acids on circulating levels of inflammatory mediators and biochemical markers in women with systemic lupus erythematosus (SLE). Experimental clinical study (clinical trial: NCT02524795); 49 women with SLE (ACR1982/1997) were randomized: 22 to the omega-3 group (daily intake of 1080mg EPA+200mg DHA, for 12 weeks) and 27 to the control group. The inflammatory mediators and biochemical markers at T0 and T1 in omega-3 group were compared using Wilcoxon test. U-Mann-Whitney test was used to compare variations of measured variables [ΔV=pre-treatment (T0)-post-treatment (T1) concentrations] between groups. p<0.05 was considered significant. The median (interquartile range - IQR) of age was 37 (29-48) years old, of disease duration was 7 (4-13) years, and of SLEDAI-2K was 1 (0-2). The median (IQR) of variation in CRP levels between the two groups showed a decrease in omega-3 group while there was an increase in control group (p=0.008). The serum concentrations of IL-6 and IL-10, leptin and adiponectin did not change after a 12 week treatment. Supplementation with omega-3 had no impact on serum concentrations of IL-6, IL-10, leptin and adiponectin in women with SLE and low disease activity. There was a significant decrease of CRP levels as well as evidence that omega-3 may impact total and LDL-cholesterol. Copyright © 2016. Published by Elsevier Editora Ltda.

Salivary inflammatory markers and microbiome in normoglycemic lean and obese children compared to obese children with type 2 diabetes.

PubMed

Janem, Waleed F; Scannapieco, Frank A; Sabharwal, Amarpeet; Tsompana, Maria; Berman, Harvey A; Haase, Elaine M; Miecznikowski, Jeffrey C; Mastrandrea, Lucy D

2017-01-01

There is emerging evidence linking diabetes with periodontal disease. Diabetes is a well-recognized risk factor for periodontal disease. Conversely, pro-inflammatory molecules released by periodontally-diseased tissues may enter the circulation to induce insulin resistance. While this association has been demonstrated in adults, there is little information regarding periodontal status in obese children with and without type 2 diabetes (T2D). We hypothesized that children with T2D have higher rates of gingivitis, elevated salivary inflammatory markers, and an altered salivary microbiome compared to children without T2D. Three pediatric cohorts ages 10-19 years were studied: lean (normal weight-C), obese (Ob), and obese with T2D (T2D). Each subject completed an oral health survey, received a clinical oral examination, and provided unstimulated saliva for measurement of inflammatory markers and microbiome analysis. The diabetes group was less likely to have had a dental visit within the last six months. Body mass index (BMI) Z-scores and waist circumference/height ratios were similar between Ob and T2D cohorts. The number of carious lesions and fillings were similar for all three groups. The gingival index was greater in the T2D group compared to the Ob and C groups. Although salivary microbial diversity was minimal between groups, a few differences in bacterial genus composition were noted. Obese children with T2D show a trend toward poorer oral health compared to normal weight and obese children without T2D. This study characterizes the salivary microbiome of children with and without obesity and T2D. This study supports a modest link between T2D and periodontal inflammation in the pediatric population.

Implication of Progranulin and C1q/TNF-Related Protein-3 (CTRP3) on Inflammation and Atherosclerosis in Subjects with or without Metabolic Syndrome

PubMed Central

Yoo, Hye Jin; Hwang, Soon Young; Hong, Ho Cheol; Choi, Hae Yoon; Yang, Sae Jeong; Choi, Dong Seop; Baik, Sei Hyun; Blüher, Matthias

2013-01-01

Objective Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance. Research Design and Methods We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT). Results Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = −0.21), diastolic blood pressure (r = −0.21), fasting glucose (r = −0.20), triglyceride (r = −0.34), total cholesterol (r = −0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R 2 = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R 2 = 0.365). Conclusions Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome. Trial Registration ClinicalTrials.gov NCT01668888 PMID:23409033

Implication of progranulin and C1q/TNF-related protein-3 (CTRP3) on inflammation and atherosclerosis in subjects with or without metabolic syndrome.

PubMed

Yoo, Hye Jin; Hwang, Soon Young; Hong, Ho Cheol; Choi, Hae Yoon; Yang, Sae Jeong; Choi, Dong Seop; Baik, Sei Hyun; Blüher, Matthias; Youn, Byung-Soo; Choi, Kyung Mook

2013-01-01

Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance. We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT). Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = -0.21), diastolic blood pressure (r = -0.21), fasting glucose (r = -0.20), triglyceride (r = -0.34), total cholesterol (r = -0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R(2) = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R(2) = 0.365). Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome. ClinicalTrials.gov NCT01668888.

Inflammatory response in multiple organs in a mouse model of acute alcohol intoxication and burn injury*

PubMed Central

Li, Xiaoling; Akhtar, Suhail; Kovacs, Elizabeth J.; Gamelli, Richard L.; Choudhry, Mashkoor A.

2011-01-01

The present study characterized the inflammatory response following burn injury and determined whether ethanol (EtOH) intoxication at the time of burn injury influences this response. To accomplish this, male mice were gavaged with EtOH (2.9 g/Kg) 4 hours prior to 12–15% total body surface area sham or burn injury. Mice were sacrificed on day one after injury; blood, small intestine, lung and liver were collected to measure IL-6, IL-10, IL-18 and MCP-1 levels. In addition, neutrophil infiltration, MPO activity and edema formation were also measured in the small intestine, lung and liver. There was no difference in the inflammatory markers in the small intestine, lung and liver in mice receiving either sham or burn injury alone except IL-6 which was increased in all 4 tissue compartments following burn injury alone. However, as compared to EtOH or burn injury alone, EtOH combined with burn injury resulted in a significant increase in cytokines, neutrophil infiltration, MPO activity and edema in the small intestine, liver and lung tissue. Furthermore, a significant increase in IL-6 and MCP-1 was observed in circulation following EtOH and burn injury compared to either EtOH intoxication or burn injury alone, no other cytokines were detected in circulation. These findings suggest that acute EtOH intoxication exacerbates the inflammatory response following burn injury. PMID:21593683

Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review.

PubMed

Agbalalah, Tari; Hughes, Stephen F; Freeborn, Ellen J; Mushtaq, Sohail

2017-10-01

This systematic review aims to evaluate randomised controlled trials (RCTs) investigating the effect of vitamin D supplementation on endothelial function and inflammation in adults. An electronic search of published randomised controlled trials, using Cochrane, Pubmed and Medline databases was conducted, with the search terms related to vitamin D and endothelial function. Inclusion criteria were RCTs in adult humans with a measure of vitamin D status using serum/plasma 25(OH)D and studies which administered the intervention through the oral route. Among the 1107 studies retrieved, 29 studies met the full inclusion criteria for this systematic review. Overall, 8 studies reported significant improvements in the endothelial/inflammatory biomarkers/parameters measured. However, in 2 out of the 8 studies, improvements were reported at interim time points, but improvements were absent post-intervention. The remaining 21 trial studies did not show significant improvements in the markers of interest measured. Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults, results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters. This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Relationship between inflammatory markers of cardiovascular disease and VO2peak in asymptomatic females.

PubMed

Omran Simin, F; Narges, Z; Sajad, A; Parisa, Y; Omrani Vahid, F

2013-04-01

The objective of this study was to investigate the relationship between inflammatory markers of cardiovascular disease (IL-6 and acute-phase reactants) and VO2peak in asymptomatic females. Study subjects were females not affected by coronary heart diseases. Forty healthy female subjects (age, 45±4.2 years; height, 161±3.5 cm; weight, 65±3.1 kg; history of regular physical activity, 5.2±0.45 years) participated in this study Analysis of data was carried out by Pearson's correlation. Statistical analysis of data indicated a negative significant relationship between IL-6 and VO2peak (r=-0.48, r2=0.23, P<0.048), CRP and VO2peak (r=-0.40, r2= 0.16, P<0.002), fibrinogen and VO2peak (r=-0.42, r2=0.17, P<0.001), and WBC and VO2peak (r=-0.22, r2=0.04, P<0.044). In conclusion higher circulating levels of IL-6, CRP and fibrinogen are associated with lower VO2peak in females.

Sleep characteristics as predictor variables of stress systems markers in insomnia disorder.

PubMed

Floam, Samantha; Simpson, Norah; Nemeth, Emese; Scott-Sutherland, Jennifer; Gautam, Shiva; Haack, Monika

2015-06-01

This study investigates the extent to which sleep characteristics serve as predictor variables for inflammatory, hypothalamic-pituitary-adrenal and autonomic systems markers. Twenty-nine participants with a diagnosis of insomnia disorder based on the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (age 25.3 ± 1.6 years, insomnia duration 6.6 ± 0.8 years) and 19 healthy control sleepers (age 25.4 ± 1.4 years) underwent a 2-week at-home evaluation keeping a sleep diary and wearing an actigraph, followed by a visit to the Research Center to measure blood pressure, and collect blood and urine samples. The actigraphy- and diary-based variables of sleep duration, sleep-onset latency, wake after sleep onset and sleep fragmentation/number of night-time awakenings were averaged and entered as dependent variables in regression analyses. Composite scores were calculated for the autonomic (blood pressure, norepinephrine), inflammatory (monocyte counts, interleukin-6, C-reactive protein) and hypothalamic-pituitary-adrenal systems (cortisol), and used as predictor variables in regression models. Compared with controls, individuals with insomnia had a shorter sleep duration (P < 0.05), and a higher hypothalamic-pituitary-adrenal and inflammatory composite score (P < 0.05). The higher inflammatory score was mainly due to higher circulating monocytes (P < 0.05), rather than differences in interleukin-6 or C-reactive protein. In persistent insomnia disorder, cortisol is upregulated and associated with actigraphy- and diary-based wake after sleep onset, suggesting that wake after sleep onset may serve as a marker to identify individuals at increased risks for disorders associated with a hyperactive hypothalamic-pituitary-adrenal system. The absence of autonomic and pro-inflammatory changes (interleukin-6, C-reactive protein), despite a substantial decrease in actigraphic sleep duration, may relate to a higher resilience to the adverse biological consequences of insomnia in this young age group. © 2014 European Sleep Research Society.

Exposure to Traffic-Related Air Pollution and Serum Inflammatory Cytokines in Children

PubMed Central

Merid, Simon Kebede; Gref, Anna; Gajulapuri, Ashwini; Lemonnier, Nathanaël; Ballereau, Stéphane; Gigante, Bruna; Kere, Juha; Auffray, Charles; Melén, Erik; Pershagen, Göran

2017-01-01

Background: Long-term exposure to ambient air pollution can lead to adverse health effects in children; however, underlying biological mechanisms are not fully understood. Objectives: We evaluated the effect of air pollution exposure during different time periods on mRNA expression as well as circulating levels of inflammatory cytokines in children. Methods: We measured a panel of 10 inflammatory markers in peripheral blood samples from 670 8-y-old children in the Barn/Child, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) birth cohort. Outdoor concentrations of nitrogen dioxide (NO2) and particulate matter (PM) with aerodynamic diameter <10μm (PM10) from road traffic were estimated for residential, daycare, and school addresses using dispersion modeling. Time-weighted average exposures during infancy and at biosampling were linked to serum cytokine levels using linear regression analysis. Furthermore, gene expression data from 16-year-olds in BAMSE (n=238) were used to evaluate links between air pollution exposure and expression of genes coding for the studied inflammatory markers. Results: A 10 μg/m3 increase of NO2 exposure during infancy was associated with a 13.6% (95% confidence interval (CI): 0.8; 28.1%) increase in interleukin-6 (IL-6) levels, as well as with a 27.8% (95% CI: 4.6, 56.2%) increase in IL-10 levels, the latter limited to children with asthma. However, no clear associations were observed for current exposure. Results were similar using PM10, which showed a high correlation with NO2. The functional analysis identified several differentially expressed genes in response to air pollution exposure during infancy, including IL10, IL13, and TNF. Conclusion: Our results indicate alterations in systemic inflammatory markers in 8-y-old children in relation to early-life exposure to traffic-related air pollution. https://doi.org/10.1289/EHP460 PMID:28669936

Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.

PubMed

Jones, Gregory T; Phillips, L Victoria; Williams, Michael J A; van Rij, Andre M; Kabir, Tasnuva D

2016-04-28

Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA. Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T-cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP-1b), had increased expression in AAA, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA-free controls (n=970) suggested a (risk factor adjusted) AAA-association with eotaxin, RANTES, and high sensitivity C-reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI, 3.5-6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking. Contrary to reports suggesting a distinct T helper 2-associated inflammatory profile in AAA, this current study suggests a more-generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as AAA biomarkers. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Oral involvement in a case of AA amyloidosis: a case report

PubMed Central

2010-01-01

Introduction Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein causes systemic amyloidosis, a serious inflammatory disorder. We document a male patient who developed reactive amyloidosis (AA type), most likely secondary to his long standing periodontitis. Case presentation A 67-year-old Turkish man complained of pain in his oral cavity (burning mouth) especially on the tongue, and had difficulty chewing and swallowing foods. A careful dental/periodontal examination was performed, including assessment of plaque, gingival condition and periodontal probing depths on all his remaining teeth. Prosthetic rehabilitation was provided three months after the completion of his periodontal and surgical therapy. The concentration of serum inflammatory markers including erythrocyte sedimentation rate, white blood cell count, fibrinogen and high sensitive C-reactive protein were measured at baseline, at the second and sixth weeks, and at three and six months after the periodontal and surgical therapy. Conclusions Oral examination revealed a few papules on the dorsum of the tongue with two slightly painful, small ulcers, localized on the vestibule of the mouth. The mean probing depth was 9.10 ± 0.84 mm. Biopsies of the tongue, buccal mucosa and retromolar trigone were performed and amyloid deposits were found. The serum inflammatory markers improved more dramatically at the second week of periodontal therapy than any other time intervals. Amyloidosis may manifest as periodontal destruction that leads to severe chronic periodontitis. Proper periodontal treatment may alleviate systemic inflammatory mediators caused by the amyloidosis. PMID:20591157

Microparticles Mediate Hepatic Ischemia-Reperfusion Injury and Are the Targets of Diannexin (ASP8597)

PubMed Central

Wong, Heng Jian; Croft, Kevin; Mori, Trevor; Farrell, Geoffrey C.

2014-01-01

Background & Aims Ischemia–reperfusion injury (IRI) can cause hepatic failure after liver surgery or transplantation. IRI causes oxidative stress, which injures sinusoidal endothelial cells (SECs), leading to recruitment and activation of Kupffer cells, platelets and microcirculatory impairment. We investigated whether injured SECs and other cell types release microparticles during post-ischemic reperfusion, and whether such microparticles have pro-inflammatory, platelet-activating and pro-injurious effects that could contribute to IRI pathogenesis. Methods C57BL6 mice underwent 60 min of partial hepatic ischemia followed by 15 min–24 hrs of reperfusion. We collected blood and liver samples, isolated circulating microparticles, and determined protein and lipid content. To establish mechanism for microparticle production, we subjected murine primary hepatocytes to hypoxia-reoxygenation. Because microparticles express everted phosphatidylserine residues that are the target of annexin V, we analyzed the effects of an annexin V-homodimer (Diannexin or ASP8597) on post-ischemia microparticle production and function. Results Microparticles were detected in the circulation 15–30 min after post-ischemic reperfusion, and contained markers of SECs, platelets, natural killer T cells, and CD8+ cells; 4 hrs later, they contained markers of macrophages. Microparticles contained F2-isoprostanes, indicating oxidative damage to membrane lipids. Injection of mice with TNF-α increased microparticle formation, whereas Diannexin substantially reduced microparticle release and prevented IRI. Hypoxia-re-oxygenation generated microparticles from primary hepatocytes by processes that involved oxidative stress. Exposing cultured hepatocytes to preparations of microparticles isolated from the circulation during IRI caused injury involving mitochondrial membrane permeability transition. Microparticles also activated platelets and induced neutrophil migration in vitro. The inflammatory properties of microparticles involved activation of NF-κB and JNK, increased expression of E-selectin, P-selectin, ICAM-1 and VCAM-1. All these processes were blocked by coating microparticles with Diannexin. Conclusions Following hepatic IRI, microparticles circulate and can be taken up by hepatocytes, where they activate signaling pathways that mediate inflammation and hepatocyte injury. Diannexin prevents microparticle formation and subsequent inflammation. PMID:25222287

Higher Circulating Leukocytes in Women with PCOS is Reversed by Aerobic Exercise

PubMed Central

Covington, Jeffrey D.; Tam, Charmaine S.; Pasarica, Magdalena; Redman, Leanne M.

2014-01-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r= -0.73, p=0.03; and r= -0.82, p=0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. PMID:25446648

Proinflammatory state and circulating erythropoietin in persons with and without anemia.

PubMed

Ferrucci, Luigi; Guralnik, Jack M; Woodman, Richard C; Bandinelli, Stefania; Lauretani, Fulvio; Corsi, Anna Maria; Chaves, Paulo H M; Ershler, William B; Longo, Dan L

2005-11-01

High circulating levels of proinflammatory cytokines cause anemia, perhaps by interacting with erythropoietin production or biological activity. We characterize the relationships of systemic inflammation, erythropoietin, and hemoglobin. Data are from the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study population. A sample of 1270 persons aged 65 years or older and 30 men and 30 women from each age-decade 20 to 70 years were randomly selected from the residents in the Chianti, Italy, geographic area. Of the 1714 eligible persons, 1235 had complete data on inflammatory markers, erythropoietin, hemoglobin, potential causes of anemia, and other relevant covariates. Anemia was defined as hemoglobin less than 12 g/dL in women and less than 13 g/dL in men. Independent of age, sex, and hemoglobin, the number of elevated inflammatory markers (C-reactive protein, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha) was associated with progressively higher erythropoietin in non-anemic participants but lower erythropoietin in anemic participants. Findings were consistent across different causes of anemia. The threshold at which the effect of inflammation on erythropoietin reversed was close to 13.0 g/dL of hemoglobin. Our findings suggest that anemia of inflammation evolves from a "pre-anemic" stage characterized by a compensatory increment of erythropoietin that maintains normal hemoglobin levels to a stage of clinically evident anemia in which erythropoietin levels are not high enough to maintain normal hemoglobin, possibly because of the inhibitory effect of inflammation on erythropoietin production. This hypothesis requires testing in a longitudinal study.

Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.

PubMed

Brooks, Marjory B; Turk, James R; Guerrero, Abraham; Narayanan, Padma K; Nolan, John P; Besteman, Elizabeth G; Wilson, Dennis W; Thomas, Roberta A; Fishman, Cindy E; Thompson, Karol L; Ellinger-Ziegelbauer, Heidrun; Pierson, Jennifer B; Paulman, April; Chiang, Alan Y; Schultze, Albert E

2017-01-01

Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions.

Analysis of circulating angiopoietin-like protein 3 and genetic variants in lipid metabolism and liver health: the DiOGenes study.

PubMed

Hess, Anne Lundby; Carayol, Jérôme; Blædel, Trine; Hager, Jörg; Di Cara, Alessandro; Astrup, Arne; Saris, Wim H M; Larsen, Lesli Hingstrup; Valsesia, Armand

2018-01-01

Angiopoietin-like protein 3 (ANGPTL3), a liver-derived protein, plays an important role in the lipid and lipoprotein metabolism. Using data available from the DiOGenes study, we assessed the link with clinical improvements (weight, plasma lipid, and insulin levels) and changes in liver markers, alanine aminotransferase, aspartate aminotransferase (AST), adiponectin, fetuin A and B, and cytokeratin 18 (CK-18), upon low-calorie diet (LCD) intervention. We also examined the role of genetic variation in determining the level of circulating ANGPTL3 and the relation between the identified genetic markers and markers of hepatic steatosis. DiOGenes is a multicenter, controlled dietary intervention where obese participants followed an 8-week LCD (800 kcal/day, using a meal replacement product). Plasma ANGPTL3 and liver markers were measured using the SomaLogic (Boulder, CO) platform. Protein quantitative trait locus (pQTL) analyses assessed the link between more than four million common variants and the level of circulating ANGPTL3 at baseline and changes in levels during the LCD intervention. Changes in ANGPTL3 during weight loss showed only marginal association with changes in triglycerides (nominal p  = 0.02) and insulin ( p  = 0.04); these results did not remain significant after correcting for multiple testing. However, significant association (after multiple-testing correction) were observed between changes in ANGPTL3 and AST during weight loss ( p  = 0.004) and between ANGPTL3 and CK-18 (baseline p  = 1.03 × 10 -7 , during weight loss p  = 1.47 × 10 -13 ). Our pQTL study identified two loci significantly associated with changes in ANGPTL3. One of these loci (the APOA4 - APOA5-ZNF259 - BUD13 gene cluster) also displayed significant association with changes in CK-18 levels during weight loss ( p  = 0.007). We clarify the link between circulating levels of ANGPTL3 and specific markers of liver function. We demonstrate that changes in ANGPLT3 and CK-18 during LCD are under genetic control from trans -acting variants. Our results suggest an extended function of ANGPTL3 in the inflammatory state of liver steatosis and toward liver metabolic processes.

Exercise in fibromyalgia and related inflammatory disorders: known effects and unknown chances.

PubMed

Ortega, E; García, J J; Bote, M E; Martín-Cordero, L; Escalante, Y; Saavedra, J M; Northoff, H; Giraldo, E

2009-01-01

Fibromyalgia (FM) is characterised by chronic widespread pain and allodynia (pain from stimuli which are not normally painful with pain that may occur other than in the area stimulated) of more than 3 months duration. The current hypothesis of the aetiology of FM includes inflammatory and neuroendocrine disorders. The biophysiology of this syndrome, however; remains still widely elusive, and there are no formally approved therapies. Non-pharmacological interventions in FM patients include habitual exercise programs which improve physical function and quality of life of patients and may even reduce pain. However the mechanisms through which exercise benefits FM symptoms needs to be elucidated. In this article we firstly review the main topics and characteristics of the FM syndrome, while focusing our attention on the inflammatory hypothesis of FM, as well as on the beneficial effects of habitual exercise as a co-therapy for FM patients. In this context, the latest developments in research on anti-inflammatory effects of exercise are also reviewed and discussed. To find out what is known about the connection between benefits of exercise for FM and anti-inflammatory effects of exercise, we carried out a PubMed search using the term "fibromyalgia" and "exercise" together with "inflammation", and no more than ten published articles were found (six of them reviews), which are also discussed. In the second part of the article we present a pilot investigation on a group of 14 female FM patients with a diagnosis of FM by a rheumatologist. They took part in a pool-aquatic program in warm water over a period of fourth months (three weekly 60-min sessions). Circulating inflammatory (IL-1beta, IL-2, IFNgamma, TNFalpha, IL-8, IL-6, IL-4, IL-10 and CRP) and neuroendocrine (NA and cortisol) markers were determined. FM patients showed higher circulating levels of IL-8, IFNgamma and CRP as well as cortisol and NA than age-matched healthy control women. After the exercise program, a significant decrease in IL-8, IFNgamma, and CRP were found, in parallel with a decrease in circulating concentrations of cortisol and increased levels of NA. The results confirm an elevated "inflammatory status" in the FM syndrome and strengthen the hypothesis that the benefits of exercise in FM patients are mediated, at least in part, by its anti-inflammatory effects. A better regulation of the cytokine-HPA axis feedback may be also involved.

PPAR-γ in the Cardiovascular System

PubMed Central

Duan, Sheng Zhong; Ivashchenko, Christine Y.; Usher, Michael G.; Mortensen, Richard M.

2008-01-01

Peroxisome proliferator-activated receptor-γ (PPAR-γ), an essential transcriptional mediator of adipogenesis, lipid metabolism, insulin sensitivity, and glucose homeostasis, is increasingly recognized as a key player in inflammatory cells and in cardiovascular diseases (CVD) such as hypertension, cardiac hypertrophy, congestive heart failure, and atherosclerosis. PPAR-γ agonists, the thiazolidinediones (TZDs), increase insulin sensitivity, lower blood glucose, decrease circulating free fatty acids and triglycerides, lower blood pressure, reduce inflammatory markers, and reduce atherosclerosis in insulin-resistant patients and animal models. Human genetic studies on PPAR-γ have revealed that functional changes in this nuclear receptor are associated with CVD. Recent controversial clinical studies raise the question of deleterious action of PPAR-γ agonists on the cardiovascular system. These complex interactions of metabolic responsive factors and cardiovascular disease promise to be important areas of focus for the future. PMID:18288291

Retinol Binding Protein 4 in children with Inflammatory Bowel Disease: a negative correlation with the disease activity.

PubMed

Roma, E; Krini, M; Hantzi, E; Sakka, S; Panayiotou, I; Margeli, A; Papassotiriou, I; Kanaka-Gantenbein, C

2012-10-01

Retinol Binding Protein-4 (RBP-4), the action of which was initially thought to be only the transport of vitamin A, is a major circulating adipocytokine involved in the inflammation. We evaluated the serum RBP-4 levels in children with inflammatory bowel disease (IBD) and correlated them with transthyretin (TTR), inflammation markers, disease activity, and body mass index (BMI). In 41 children of mean age 11.9 ± 3.6 years (range 5-17.7 y) with IBD (19 with Crohn's disease (CD) and 22 with Ulcerative colitis (UC) serum RBP-4, TTR, Amyloid A (SAA), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), disease activity and BMI were prospectively determined and compared with those of 42 matched controls. No difference in the RBP-4 and TTR serum levels, between patients and controls as well as between active and remission state of the disease was noticed. A negative correlation of serum RBP-4 with the disease activity, SAA and ESR and a positive correlation with TTR was found, but no significant correlation with CRP or BMI was found. Inflammation markers were significantly increased in patients compared to controls and had a positive correlation with the disease activity. RBP-4 negatively correlated with disease activity of children with IBD probably indicating a protective anti-inflammatory mechanism of action in addition to transport of vitamin A.

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

PubMed Central

Jonsdottir, Ingibjörg H.; Hägg, Daniel A.; Glise, Kristina; Ekman, Rolf

2009-01-01

Background Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. Methodology/Principal Findings Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n = 89) and controls (n = 88) showing a small but significant increase of CRP levels in the patients. Conclusions/Significance MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured. PMID:19888340

A comparative evaluation of two decompression procedures for technical diving using inflammatory responses: compartmental versus ratio deco.

PubMed

Spisni, Enzo; Marabotti, Claudio; De Fazio, Luigia; Valerii, Maria Chiara; Cavazza, Elena; Brambilla, Stefano; Hoxha, Klarida; L'Abbate, Antonio; Longobardi, Pasquale

2017-03-01

The aim of this study was to compare two decompression procedures commonly adopted by technical divers: the ZH-L16 algorithm modified by 30/85 gradient factors (compartmental decompression model, CDM) versus the 'ratio decompression strategy' (RDS). The comparison was based on an analysis of changes in diver circulating inflammatory profiles caused by decompression from a single dive. Fifty-one technical divers performed a single trimix dive to 50 metres' sea water (msw) for 25 minutes followed by enriched air (EAN50) and oxygen decompression. Twenty-three divers decompressed according to a CDM schedule and 28 divers decompressed according to a RDS schedule. Peripheral blood for detection of inflammatory markers was collected before and 90 min after diving. Venous gas emboli were measured 30 min after diving using 2D echocardiography. Matched groups of 23 recreational divers (dive to 30 msw; 25 min) and 25 swimmers were also enrolled as control groups to assess the effects of decompression from a standard air dive or of exercise alone on the inflammatory profile. Echocardiography at the single 30 min observation post dive showed no significant differences between the two decompression procedures. Divers adopting the RDS showed a worsening of post-dive inflammatory profile compared to the CDM group, with significant increases in circulating chemokines CCL2 (P = 0.001) and CCL5 (P = 0.006) levels. There was no increase in chemokines following the CDM decompression. The air scuba group also showed a statistically significant increase in CCL2 (P < 0.001) and CCL5 (P = 0.003) levels post dive. No cases of decompression sickness occurred. The ratio deco strategy did not confer any benefit in terms of bubbles but showed the disadvantage of increased decompression-associated secretion of inflammatory chemokines involved in the development of vascular damage.

Acute Immune-Inflammatory Responses to a Single Bout of Aerobic Exercise in Smokers; The Effect of Smoking History and Status

PubMed Central

Kastelein, Tegan Emma; Duffield, Rob; Marino, Frank E.

2015-01-01

This study examined the acute immune and inflammatory responses to exercise in smokers compared to non-smokers, and further, the effect of smoking history on these immune-inflammatory responses. Fifty-four recreationally active males who were either smokers (SM; n = 27) or non-smokers (NS; n = 27) were allocated into either young (YSM, YNS) or middle-aged groups (MSM, MNS) based on smoking status. Participants were matched for fitness and smoking habits and following familiarization and baseline testing, undertook an exercise protocol that involved 40 min of cycle ergometry at 50% of VO2peak. Venous blood was obtained pre- and post- (0 min, 1, and 4 h) exercise to measure circulating leukocytes and inflammatory markers interleukin (IL)-6, IL-1β, IL-1ra, and monocyte chemoattractant protein-1 (MCP-1). Compared to MNS, MSM showed elevated basal concentrations of MCP-1, which were increased with a longer smoking history (P < 0.05). In response to exercise, YSM demonstrated an amplified IL-6 response from immediately- to 1 h-post compared to YNS. Furthermore, IL-1ra in YSM was elevated above that of YNS across all time points (P < 0.05). The MSM group had higher IL-1β at baseline when compared to YSM, although IL-1ra was greater for YSM at baseline (P < 0.05). Finally, the post-exercise leukocyte response was greater in MSM compared to YSM and non-smokers (P < 0.05). In conclusion, smoker’s exhibit elevated MCP-1 and IL-1β that seem to be evident with a longer smoking history (~15 years). Furthermore, the differences in exercise-induced inflammatory responses noted in YSM may be indicative tobacco smoke exposure priming circulating leukocytes to amplify inflammatory responses. PMID:26779179

Inflammatory markers in relation to body composition, physical activity and assessment of nutritional status of the adolescents.

PubMed

Neves Miranda, Valter Paulo; Gouveia Peluzio, Maria do Carmo; Rodrigues de Faria, Eliana; Castro Franceschini, Sylvia do Carmo; Eloiza Priore, Silvia

2015-05-01

The evaluation of inflammatory markers during adolescence can monitor different stages and manifestation of chronic diseases in adulthood. The control of the subclinical inflammation process through changes in lifestyle, especially in the practice of physical activity and dietary education can mitigate the effects of risk factors that trigger the process of atherosclerosis. To do a critical review regarding inflammatory markers as a risk factor of cardiovascular disease in relation to body composition, physical activity and assessment of nutritional status of adolescents. A literature review was performed in the following electronic databases: PUBMED, SCIELO and CONCHRANE COLLECTION. The following associated terms were used "inflammation AND cardiovascular diseases AND nutritional status OR body composition OR physical activity". There were topics created for the discussion of subjects: obesity and risk factors for cardiovascular disease during adolescence; expression of inflammatory markers in adolescence; development of cardiovascular disease with inflammatory markers, and finally, inflammatory markers, physical activity and nutritional evaluation. It was observed that the inflammatory markers may manifest in adolescence and be related to risk factors for cardiovascular diseases. Physical activity and nutritional evaluation featured as non-pharmacological measures to control the incidence of inflammatory markers and cardiovascular risk factor. Intervention studies may clarify how the adoption of a more proper lifestyle can influence the inflammatory process. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Associations between Markers of Inflammation and Physiological and Pharmacological Levels of Circulating Sex Hormones in Postmenopausal Women

PubMed Central

Karim, Roksana; Stanczyk, Frank Z.; Hodis, Howard N.; Cushman, Mary; Lobo, Roger A.; Hwang, Juliana; Mack, Wendy J.

2010-01-01

Objective Hormone therapy has been shown to reduce markers of vascular inflammation in postmenopausal women. C-reactive protein (CRP), a marker of generalized inflammation, is raised by oral estradiol therapy. It is not known how sex hormone concentrations relate to the markers of inflammation in postmenopausal women taking or not taking hormone therapy. Methods This observational study includes postmenopausal women participating in the Estrogen in the Prevention of Atherosclerosis Trial (EPAT). Multiple measures of serum sex hormone and sex hormone binding globulin (SHBG) levels from 107 postmenopausal women taking oral estradiol therapy (ET) and 109 taking placebo over 2 years were correlated with markers of inflammation over the same time period using generalized estimating equations. Results Levels of soluble intercellular adhesion molecule-1 (sICAM-1) were significantly inversely associated with estrone (p = 0.05), total and free estradiol (p = 0.008 and 0.02, respectively), and SHBG (p = 0.03) only among oral ET users. Serum homocysteine levels were also inversely associated with estrone (p = 0.0001), total and free estradiol (p = 0.0006 and 0.0009, respectively) in ET-treated women only. No such associations were observed among women taking placebo. C-reactive protein (CRP) was positively associated with estrogens and SHBG among women taking oral ET but inversely associated with SHBG among the placebo group. Conclusions The inverse associations of estrogens with sICAM-1, and homocysteine support an anti-inflammatory property of estrogen, which was only observed at pharmacologic levels in postmenopausal women. The positive associations between estrogens and CRP in the ET-treated women can be explained by the first-pass hepatic effect rather than a pro-inflammatory response. PMID:20632462

Sleep Variability, Health-Related Practices and Inflammatory Markers in a Community Dwelling Sample of Older Adults

PubMed Central

Okun, Michele L.; Reynolds, Charles F.; Buysse, Daniel J.; Monk, Timothy H; Mazumdar, Sati; Begley, Amy; Hall, Martica

2011-01-01

Background Low-grade chronic inflammation is an important risk factor for age-related morbidity. Health behaviors, including average aggregate measures of sleep, have been linked to increased inflammation in older adults. Variability in sleep timing may also be associated with increased inflammation. This study evaluated relationships among several health behaviors and circulating proinflammatory cytokines (IL-6 and TNF-α). Method Participants were community dwelling older adults >60 years (N = 222: 39 bereaved, 55 caregivers, 52 with insomnia, and 76 good sleepers). Mean values and intra-individual variability in sleep, as well as caffeine and alcohol use, exercise, and daytime napping were assessed by sleep diaries. Blood draws were obtained in the morning. Results Several interactions were noted between sleep behaviors, inflammatory markers, and participant group. Greater variability in wake time and time in bed was associated with higher IL-6 among good sleepers relative to caregivers and older adults with insomnia. Good sleepers who consumed moderate amounts of alcohol had the lowest concentrations of IL-6 compared to the other three groups who consumed alcohol. Insomnia subjects, but not good sleepers, showed increased concentrations of IL-6 associated with caffeine use. Caregivers showed increased concentrations of TNF-α with alcohol use relative to good sleepers. Greater variability in bedtime, later wake times and longer time in bed was associated with higher TNF-α regardless of group. Conclusions Moderation and regularity in the practice of certain health behaviors, including sleep practices, were associated with lower plasma levels of inflammatory markers in older adults. Life circumstances and specific sleep disorders may modify these associations. PMID:21097658

Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

PubMed

Lee, Miryoung; Czerwinski, Stefan A; Choh, Audrey C; Demerath, Ellen W; Sun, Shumei S; Chumlea, Wm C; Towne, Bradford; Siervogel, Roger M

2006-03-01

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis.

PubMed

Hammana, I; Malet, A; Costa, M; Brochiero, E; Berthiaume, Y; Potvin, S; Chiasson, J-L; Coderre, L; Rabasa-Lhoret, R

2007-06-01

Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.

Worse inflammatory profile in omnivores than in vegetarians associates with the gut microbiota composition.

PubMed

Franco-de-Moraes, Ana Carolina; de Almeida-Pititto, Bianca; da Rocha Fernandes, Gabriel; Gomes, Everton Padilha; da Costa Pereira, Alexandre; Ferreira, Sandra Roberta G

2017-01-01

To describe the abundance of major phyla and some genera in the gut microbiota of individuals according to dietary habits and examine their associations with inflammatory markers, insulin resistance, and cardiovascular risk profile. A total of 268 non-diabetic individuals were stratified into groups of dietary types (strict vegetarians, lacto-ovo-vegetarians, and omnivores). The taxonomic composition and phylogenetic structure of the microbiota were obtained through the analysis of the 16S rRNA gene. Samples were clustered into operational taxonomic units at 97% similarity using GreenGenes 13.5 database. Clinical, biochemical, and circulating inflammatory markers were compared by ANOVA or Kruskal-Wallis test. The sample (54.2% women, mean age 49.5 years) was composed of 66 strict vegetarians, 102 lacto-ovo-vegetarians and 100 omnivores. Considering the entire sample, the greatest abundant phyla were Firmicutes (40.7 ± 15.9%) and Bacteroidetes (39.5 ± 19.9%), and no difference in abundances was found between individuals with normal and excess weight. Stratifying by dietary types, the proportion of Firmicutes was lower and of Bacteroidetes was higher in strict vegetarians when compared to lacto-ovo-vegetarians and omnivores. At the genus level, strict vegetarians had a higher Prevotella abundance and Prevotella/Bacteroides ratio than the other groups. They also had a lower proportion of Faecalibacterium than lacto-ovo-vegetarians, and both vegetarian groups had higher proportions than did omnivores. Succinivibrio and Halomonas from the Proteobacteria phylum were overrepresented in omnivores. The omnivorous group showed higher values of anthropometric data, insulin, HOMA-IR, and a worse lipid profile. Inflammatory markers exhibited a gradual and significant increase from the vegetarians and lacto-ovo-vegetarians to the omnivorous group. There are differences in gut microbiota composition of individuals with distinct dietary habits, who differ according to their inflammatory and metabolic profiles. Based on the findings relative to bacteria abundances and on their recognized actions in the metabolism, we suggest that exposure to animal foods may favor an intestinal environment which could trigger systemic inflammation and insulin resistance-dependent metabolic disorders.

Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.

PubMed

Yende, Sachin; D'Angelo, Gina; Kellum, John A; Weissfeld, Lisa; Fine, Jonathan; Welch, Robert D; Kong, Lan; Carter, Melinda; Angus, Derek C

2008-06-01

Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown. To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes. Prospective cohort study at 28 sites. We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Gray's survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008). Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.

A novel small animal extracorporeal circulation model for studying pathophysiology of cardiopulmonary bypass.

PubMed

Fujii, Yutaka; Shirai, Mikiyasu; Inamori, Shuji; Takewa, Yoshiaki; Tatsumi, Eisuke

2015-03-01

Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite the fact that ECCcauses damage to blood components and is non-physiologic, its pathophysiology has not been fully elucidated. This is because difficulty in clinical research and animal experiments keeps the knowledge insufficient. Therefore, it is desirable to have a miniature ECC model for small animals, which enables repetitive experiments, to study the mechanism of pathophysiological changes during ECC. We developed a miniature ECC system and applied it to the rat. We measured changes in hemodynamics, blood gases and hemoglobin (Hb) concentration, serum cytokines (TNF-α, IL-6, IL-10), biochemical markers (LDH, AST, ALT), and the wet-to-dry weight (W/D) ratio of the lung for assessing whether the rat ECC model is comparable to the human ECC. The ECC system consisted of a membranous oxygenator (polypropylene, 0.03 m(2)), tubing line (polyvinyl chloride), and roller pump. Priming volume of this system is only 8 ml. Rats (400-450 g) were divided into the SHAM group (n = 7) and the ECC group (n = 7). Blood samples were collected before, 60 and 120 min after initiation of ECC. During ECC, blood pressure and Hb were maintained around 80 mmHg and 10 g/dL, respectively. The levels of the inflammatory and biochemical markers and the W/D ratio were significantly elevated in the ECC group, indicating some organ damages and systemic inflammatory responses during ECC. We successfully established the ECC for the rat. This miniature ECC model could be a useful approach for studying the mechanism of pathophysiology during ECC and basic assessment of the ECC devices.

Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis

PubMed Central

Deshpande, Dipti; Kethireddy, Sravani; Janero, David R.; Amiji, Mansoor M.

2016-01-01

Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE)-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs) with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/-) mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease. PMID:26840601

Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome

PubMed Central

Rizza, Stefano; Muniyappa, Ranganath; Iantorno, Micaela; Kim, Jeong-a; Chen, Hui; Pullikotil, Philomena; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide; Cardillo, Carmine

2011-01-01

Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H2O2. Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. PMID:21346065

Perioperative Outcomes, Transfusion Requirements, and Inflammatory Response After Coronary Artery Bypass Grafting With Off-Pump, Mini-Extracorporeal, and On-Pump Circulation Techniques.

PubMed

Brinkman, William T; Squiers, John J; Filardo, Giovanni; Arsalan, Mani; Smith, Robert L; Moore, David; Mack, Michael J; DiMaio, J Michael

2015-12-01

Mini-extracorporeal circulation (MECC) units were developed to reduce postoperative morbidity, transfusion requirements, and inflammation associated with conventional on-pump coronary artery bypass (ONCAB) surgery without the technical demands of the off-pump (OPCAB) technique. We compared perioperative outcomes and inflammatory mediation among OPCAB, MECC, and ONCAB techniques. We prospectively enrolled 102 patients undergoing elective isolated coronary bypass grafting. Perfusion methods were OPCAB (n = 34), MECC (n = 34), and ONCAB (n = 34). Serial blood samples were collected to measure serum inflammatory markers. There were no operative deaths or strokes. Total red blood cell (RBC) products used in OPCAB, MECC, and ONCAB patients were 0.676, 1.000, and 1.235 units, respectively. Adjusted (by splined Society of Thoracic Surgeons operative risk score) analysis showed no statistically significant differences in mean RBC product use among the different operative systems (OPCAB vs MECC, P = 0.580; OPCAB vs ONCAB, P = 0.311; MECC vs ONCAB, P = 0.633). Adjusted (by Society of Thoracic Surgeons risk score and baseline level) mean plasma level differences (24 hours postoperative - baseline) of C-reactive protein for OPCAB (117.89; 95% confidence interval [95% CI], 106.23-129.54) and for MECC (124.88; 95% CI, 113.45-136.32) were significantly higher than for ONCAB (98.82; 95% CI, 86.40-111.24). No significant adjusted differences (P = 0.304) in interleukin-6 level changes were observed. Off-pump coronary artery bypass and MECC did not significantly reduce mean total RBC transfusion requirements. Off-pump coronary artery bypass and MECC were associated with greater C-reactive protein elevation than ONCAB, suggestive of an increased inflammatory response to each of these techniques.

Influence of vitamin C supplementation on oxidative stress and neutrophil inflammatory response in acute and regular exercise.

PubMed

Popovic, Ljiljana M; Mitic, Nebojsa R; Miric, Dijana; Bisevac, Boban; Miric, Mirjana; Popovic, Brankica

2015-01-01

Exercise induces a multitude of physiological and biochemical changes in blood affecting its redox status. Tissue damage resulting from exercise induces activation of inflammatory cells followed by the increased activity of myeloperoxidase (MPO) in circulation. Vitamin C readily scavenges free radicals and may thereby prevent oxidative damage of important biological macromolecules. The aim of this study was to examine the effect of vitamin C supplementation on oxidative stress and neutrophil inflammatory response induced by acute and regular exercise. Experiment was conducted on acute exercise group (performing Bruce Treadmill Protocol (BTP)) and regular training group. Markers of lipid peroxidation, malondialdehyde (MDA), MPO activity, and vitamin C status were estimated at rest and after BTP (acute exercise group) and before and after vitamin C supplementation in both groups. Our results showed increased postexercise Asc in serum independently of vitamin supplementation. They also showed that vitamin C can significantly decrease postexercise MDA level in both experimental groups. Increased postexercise MPO activity has been found in both groups and was not affected by vitamin C supplementation. We concluded that vitamin C supplementation can suppress lipid peroxidation process during exercise but cannot affect neutrophil inflammatory response in either exercise group.

Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids.

PubMed

Bower, Julienne E; Ganz, Patricia A; Aziz, Najib; Olmstead, Richard; Irwin, Michael R; Cole, Steve W

2007-03-01

Fatigue is a common problem following cancer treatment and our previous studies suggest that a chronic inflammatory process might contribute to cancer-related fatigue. However, immune responses to challenge have not yet been evaluated among individuals with cancer-related fatigue, and it is not known what mechanisms drive increased levels of inflammatory markers in fatigued cancer survivors. We have previously reported that fatigued breast cancer survivors show a blunted cortisol response to an experimental psychological stressor. In this report, we focus on inflammatory responses to this stressor and their relationship to circulating glucocorticoids and cellular sensitivity to glucocorticoid inhibition. Relative to non-fatigued control survivors, participants experiencing persistent fatigue showed significantly greater increases in LPS-stimulated production of IL-1beta and IL-6 following the stressor (Group x Time interaction: p<.05). Fatigued participants did not show any difference in cellular sensitivity to cortisol inhibition of cytokine production, but they did show significantly less salivary cortisol increase in the aftermath of the stressor. Moreover, blunted cortisol responses were associated with significantly increased production of IL-6 in response to LPS stimulation (p<.05). These data provide further evidence of enhanced inflammatory processes in fatigued breast cancer survivors and suggest that these processes may stem in part from decreased glucocorticoid response to stress.

Recovery of endocrine and inflammatory mediators following an extended energy deficit.

PubMed

Henning, Paul C; Scofield, Dennis E; Spiering, Barry A; Staab, Jeffery S; Matheny, Ronald W; Smith, Martha A; Bhasin, Shalender; Nindl, Bradley C

2014-03-01

Due to current operational requirements, elite soldiers deploy quickly after completing arduous training courses. Therefore, it is imperative that endocrine and inflammatory mediators have fully recovered. Our objective was to determine whether a short-term (2-6 wk) recovery period was sufficient to restore endocrine and inflammatory homeostasis after sustained energy deficit. Before and immediately after the course, serum concentrations of inflammatory and endocrine markers were taken along with anthropometric measures prior to and immediately after the Army Ranger course. In addition, nine soldiers were assessed between 2 and 6 weeks after the course. This research occurred in a field setting during an intensive 8-week military training course characterized by high-energy expenditure, energy restriction, and sleep deprivation (U.S. Army Ranger School). Twenty-three male soldiers (23.0 ± 2.8 y; 177.6 ± 7.9 cm; 81.0 ± 9.6 kg, 16.8 ± 3.9% body fat) participated in this study. There were no interventions used in this research. Significant changes occurred in circulating total testosterone (-70%), brain-derived neurotrophic factor (-33%), total IGF-1 (-38.7%), free IGF-1 (-41%), IGF binding protein (IGFBP-6; -23.4%), sex-hormone binding globulin (+46%), thyroid stimulating hormone (+85%), IGFBP-1 (+534.4%), IGFBP-2 (+98.3%), IGFBP-3 (+14.7%), IL-4 (+135%), IL-6 (+217%), and IL-8 (+101%). Significant changes in body mass (-8%), bicep (-14%), forearm (-5%), thigh (-7%), and calf (-2%) circumferences, sum of skinfolds (-52%), and percentage body fat (-54%). All anthropometric, inflammatory, and hormonal values, except T3, were restored to baseline levels within 2-6 weeks after the course. Endocrine markers and anthropometric measures were degraded, and inflammatory mediators increased after an extended energy deficit. A short-term recovery of 2-6 weeks was sufficient to restore these mediators.

Diet and diet combined with chronic aerobic exercise decreases body fat mass and alters plasma and adipose tissue inflammatory markers in obese women.

PubMed

Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

2013-12-01

The purpose of this study was to investigate the effect of 6 months aerobic exercise and diet alone or in combination on markers of inflammation (MOI) in circulation and in adipose abdominal tissue (AT) in obese women. Thirty obese subjects were randomized into a 24-week intervention: (1) exercise (EX), (2) diet (DI), and (3) exercise and diet (EXD). Blood samples were collected at baseline, after 12 and 24 weeks. AT biopsies were obtained only at baseline and after 24 weeks. In the EXD and DI groups, the fat loss was after 12 weeks was -13.74 and -7.8 % (P < 0.01) and after 24 weeks was -21.82 and -17 % (P < 0.01) with no changes in the EX group. After 12 and 24 weeks, maximal oxygen consumption (VO2max) was increased by 21.81-39.54 % (P < 0.05) in the EXD group and 18.09-40.95 % in the EX group with no changes in the DI group. In the EXD and DI groups, circulating levels of tumor necrosis factor α and interleukin 6 were decreased after 24 weeks for both groups (P < 0.01). No changes in the EX group. Homeostatic model assessment for insulin resistance decreased (P < 0.05) only after 24 weeks in the EXD group. In AT biopsies, subjects in the EXD and DI groups exhibited a significant decrease in MO (P < 0.01 for all). No changes in AT biopsies were found in the EX group. In conclusion, chronic aerobic exercise was found to have no effects on circulating and AT MOI despite an increased VO2max. Rather important body composition modifications were found to have beneficial effects on circulating and AT MOI in these obese women.

Circulating monocyte chemoattractant protein‐1 (MCP‐1) is associated with cachexia in treatment‐naïve pancreatic cancer patients

PubMed Central

Talbert, Erin E.; Lewis, Heather L.; Farren, Matthew R.; Ramsey, Mitchell L.; Chakedis, Jeffery M.; Rajasekera, Priyani; Haverick, Ericka; Sarna, Angela; Bloomston, Mark; Pawlik, Timothy M.; Zimmers, Teresa A.; Lesinski, Gregory B.; Hart, Phil A.; Dillhoff, Mary E.; Schmidt, Carl R.

2018-01-01

Abstract Background Cancer‐associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer‐induced cachexia in patients with earlier stages of disease. Methods A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high‐sensitivity multiplex was used for increased sensitivity for nine cytokines. Results Resectable pancreatic cancer patients with cachexia had low levels of canonical pro‐inflammatory cytokines including interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), interferon‐γ (IFN‐γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein‐1 (MCP‐1) was increased in treatment‐naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were found to be decreased in the same cohort of treatment‐naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers. Conclusions Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment‐naïve patients have higher levels of MCP‐1, suggesting that MCP‐1 may be useful as a biomarker of cancer cachexia. PMID:29316343

Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise.

PubMed

Covington, Jeffrey D; Tam, Charmaine S; Pasarica, Magdalena; Redman, Leanne M

2016-05-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r = -0.73, p = 0.03; and r = -0.82, p = 0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. Copyright © 2014 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Gestational glucocorticoid exposure disrupts glucose homeostasis that is accompanied by increased endoglin and DPP-4 activity instead of GSK-3 in rats.

PubMed

Badmus, Olufunto O; Michael, Olugbenga S; Rabiu, Saheed; Olatunji, Lawrence A

2018-04-13

Gestational glucocorticoid (GC) treatment has been associated with cardiometabolic disorder (CMD) in offspring's in later life. Elevated dipeptidyl peptidase-4 (DPP-4) activity, endoglin and glycogen synthase kinase-3 (GSK-3) has also been implicated in the development of insulin resistance (IR) and/or vascular inflammation. We aimed to investigate the impact of GC exposure on glucose metabolism and the circulating levels of inflammatory biomarkers, DPP-4 activity and GSK-3 in pregnant rats. Pregnant Wistar rats received either vehicle or dexamethasone (DEX; 0.2 mg/kg; po) between gestational days 14 and 19. Gestational GC exposure resulted in impaired glucose homeostasis that is accompanied with elevated circulating levels of inflammatory biomarkers (endoglin, uric acid, and platelet/lymphocyte ratio), oxidative stress (malondialdehyde), blood viscosity, reduced NO level and increased DPP-4 activity. However, these effects were associated with atherogenic dyslipidemia and reduced GSK-3.We conclude that plasma endoglin, a marker of vascular inflammation, and plasma DPP-4 activity are increased in pregnant rats treated with GC during late gestation. Therefore, glucose deregulation associated with gestational GC exposure is through endoglin-/DPP-4-dependent but GSK-3-independent pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.

PubMed

Borges, Maria Carolina; Barros, Aluísio J D; Ferreira, Diana L Santos; Casas, Juan Pablo; Horta, Bernardo Lessa; Kivimaki, Mika; Kumari, Meena; Menon, Usha; Gaunt, Tom R; Ben-Shlomo, Yoav; Freitas, Deise F; Oliveira, Isabel O; Gentry-Maharaj, Aleksandra; Fourkala, Evangelia; Lawlor, Debbie A; Hingorani, Aroon D

2017-12-01

Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis -acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant. © 2017 The Authors.

Do acute phase markers explain body temperature and brain temperature after ischemic stroke?

PubMed Central

Whiteley, William N.; Thomas, Ralph; Lowe, Gordon; Rumley, Ann; Karaszewski, Bartosz; Armitage, Paul; Marshall, Ian; Lymer, Katherine; Dennis, Martin

2012-01-01

Objective: Both brain and body temperature rise after stroke but the cause of each is uncertain. We investigated the relationship between circulating markers of inflammation with brain and body temperature after stroke. Methods: We recruited patients with acute ischemic stroke and measured brain temperature at hospital admission and 5 days after stroke with multivoxel magnetic resonance spectroscopic imaging in normal brain and the acute ischemic lesion (defined by diffusion-weighted imaging [DWI]). We measured body temperature with digital aural thermometers 4-hourly and drew blood daily to measure interleukin-6, C-reactive protein, and fibrinogen, for 5 days after stroke. Results: In 44 stroke patients, the mean temperature in DWI-ischemic brain soon after admission was 38.4°C (95% confidence interval [CI] 38.2–38.6), in DWI-normal brain was 37.7°C (95% CI 37.6–37.7), and mean body temperature was 36.6°C (95% CI 36.3–37.0). Higher mean levels of interleukin-6, C-reactive protein, and fibrinogen were associated with higher temperature in DWI-normal brain at admission and 5 days, and higher overall mean body temperature, but only with higher temperature in DWI-ischemic brain on admission. Conclusions: Systemic inflammation after stroke is associated with elevated temperature in normal brain and the body but not with later ischemic brain temperature. Elevated brain temperature is a potential mechanism for the poorer outcome observed in stroke patients with higher levels of circulating inflammatory markers. PMID:22744672

Chemerin as an independent predictor of cardiovascular event risk

PubMed Central

İnci, Sinan; Aksan, Gökhan; Doğan, Pınar

2016-01-01

Currently, coronary artery disease (CAD) is considered a major ailment in humans with widespread prevalence. CAD also accounts for high mortality rates around the world that involves several known risk factors. Chemerin is a novel adipokinine that is associated with inflammation and adipogenesis. Furthermore, experimental and clinical data indicate that localized as well as circulating chemerin expression and activation are elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. Chemerin is accepted as being a strong marker because the serum chemerin levels are increased in a CAD condition. However, the chimeric characteristics of chemerin have not been fully investigated. Although chemerin is known to be responsible for CAD development among other factors, authors still investigate it at the marker level. This review focuses on chemerin expression, processing, biological function and relevance to human diseases, and on the role of chemerin in the maintenance of a cardiovascular disease. PMID:27092231

Association between local inflammation and breast tissue age-related lobular involution among premenopausal and postmenopausal breast cancer patients

PubMed Central

Hanna, Mirette; Dumas, Isabelle; Orain, Michèle; Jacob, Simon; Têtu, Bernard; Sanschagrin, François; Bureau, Alexandre; Poirier, Brigitte; Diorio, Caroline

2017-01-01

Increased levels of pro-inflammatory markers and decreased levels of anti-inflammatory markers in the breast tissue can result in local inflammation. We aimed to investigate whether local inflammation in the breast tissue is associated with age-related lobular involution, a process inversely related to breast cancer risk. Levels of eleven pro- and anti-inflammatory markers were assessed by immunohistochemistry in normal breast tissue obtained from 164 pre- and postmenopausal breast cancer patients. Involution status of the breast (degree of lobular involution and the predominant lobule type) was microscopically assessed in normal breast tissue on hematoxylin-eosin stained mastectomy slides. Multivariate generalized linear models were used to assess the associations. In age-adjusted analyses, higher levels of pro-inflammatory markers IL-6, TNF-α, CRP, COX-2, leptin, SAA1 and IL-8; and anti-inflammatory marker IL-10, were inversely associated with the prevalence of complete lobular involution (all P≤0.04). Higher levels of the pro-inflammatory marker COX-2 were also associated with lower prevalence of predominant type 1/no type 3 lobules in the breast, an indicator of complete involution, in age-adjusted analysis (P = 0.017). Higher tissue levels of inflammatory markers, mainly the pro-inflammatory ones, are associated with less involuted breasts and may consequently be associated with an increased risk of developing breast cancer. PMID:28846716

Acculturative stress and inflammation among Chinese immigrant women.

PubMed

Fang, Carolyn Y; Ross, Eric A; Pathak, Harsh B; Godwin, Andrew K; Tseng, Marilyn

2014-06-01

Among Chinese immigrant populations, increasing duration of US residence is associated with elevated risk for various chronic diseases. Although life-style changes after migration have been extensively studied in immigrant populations, the psychosocial impact of acculturative stress on biological markers of health is less understood. Thus, the purpose of the present study is to examine associations between acculturative stress and inflammatory markers in a Chinese immigrant population. Study participants (n = 407 foreign-born Chinese American women) completed questionnaires assessing levels of stress, including acculturative stress and positive and negative life events in the previous year. Participant height and weight were measured using standard protocols, and blood samples were drawn for assessment of circulating serum levels of C-reactive protein (CRP) and soluble tumor necrosis factor receptor 2 (sTNFR2). Higher levels of acculturative stress were significantly associated with higher levels of CRP (B = 0.07, 95% confidence interval = 0.01-0.13, p = .031) and sTNFR2 (B = 0.02, 95% confidence interval = 0.004-0.03, p = .012), adjusting for age and body mass index. The latter association was no longer statistically significant when overall acculturation (i.e., identification with American culture) was included in the model. Life events were not associated with CRP or sTNFR2. This is one of the first studies to demonstrate that acculturative stress is associated with inflammatory markers in a Chinese immigrant population. Replication in other immigrant samples is needed to fully establish the biological correlates and clinical consequences of acculturative stress.

Maintaining brain health by monitoring inflammatory processes: a mechanism to promote successful aging.

PubMed

Rosano, Caterina; Marsland, Anna L; Gianaros, Peter J

2012-02-01

Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests that inflammation is a shared mechanism, contributing to both cognitive decline and abnormalities in brain structure and metabolism. Thus, inflammation may provide a target for intervention. Specifically, circulating inflammatory markers have been associated with declines in cognitive function and worsening of brain structural and metabolic characteristics. Additionally, it has been proposed that older brains are characterized by a sensitization to neuroinflammatory responses, even in the absence of overt disease. This increased propensity to central inflammation may contribute to poor brain health and premature brain aging. Still unknown is whether and how peripheral inflammatory factors directly contribute to decline of brain health. Human research is limited by the challenges of directly measuring neuroinflammation in vivo. This review assesses the role that inflammation may play in the brain changes that often accompany aging, focusing on relationships between peripheral inflammatory markers and brain health among well-functioning, community-dwelling adults seventy years and older. We propose that monitoring and maintaining lower levels of systemic and central inflammation among older adults could help preserve brain health and support successful aging. Hence, we also identify plausible ways and novel experimental study designs of maintaining brain health late in age through interventions that target the immune system.

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

PubMed Central

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-01-01

Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults.

PubMed

Peairs, Abigail D; Rankin, Janet W; Lee, Yong Woo

2011-11-07

Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor- α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-κB (NF-κB)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)). O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments. While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-κB responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation. © 2011 Peairs et al; licensee BioMed Central Ltd.

Taurine supplementation regulates Iκ-Bα protein expression in adipose tissue and serum IL-4 and TNF-α concentrations in MSG obesity.

PubMed

Caetano, Luiz Carlos; Bonfleur, Maria Lúcia; Ribeiro, Rosane Aparecida; Nardelli, Tarlliza Romanna; Lubaczeuski, Camila; do Nascimento da Silva, Juliana; Carneiro, Everardo Magalhães; Balbo, Sandra Lucinei

2017-03-01

Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1β or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.

Ghrelin and obestatin levels in rheumatoid arthritis.

PubMed

Koca, Suleyman Serdar; Ozgen, Metin; Aydin, Suleyman; Dag, Sait; Evren, Bahri; Isik, Ahmet

2008-10-01

Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients. Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet's disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay. Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (p<0.05 for both), but when compared with HC group differences were not significant. There was no difference across groups in terms of acylated ghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-alpha in the HC group (r=0.400, p<0.05; r=0.412, p<0.05, r=0.543, p<0.01 and r=0.528, p<0.05, respectively). Our results did not show a significant correlation between circulating ghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.

Acute high-intensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes

PubMed Central

Durrer, Cody; Francois, Monique; Neudorf, Helena

2017-01-01

Type 2 diabetes (T2D) is characterized by chronic low-grade inflammation that contributes to disease pathophysiology. Exercise has anti-inflammatory effects, but the impact of high-intensity interval training (HIIT) is not known. The purpose of this study was to determine the impact of a single session of HIIT on cellular, molecular, and circulating markers of inflammation in individuals with T2D. Participants with T2D (n = 10) and healthy age-matched controls (HC; n = 9) completed an acute bout of HIIT (7 × 1 min at ~85% maximal aerobic power output, separated by 1 min of recovery) on a cycle ergometer with blood samples obtained before (Pre), immediately after (Post), and at 1 h of recovery (1-h Post). Inflammatory markers on leukocytes were measured by flow cytometry, and TNF-α was assessed in both LPS-stimulated whole blood cultures and plasma. A single session of HIIT had an overall anti-inflammatory effect, as evidenced by 1) significantly lower levels of Toll-like receptor (TLR) 2 surface protein expression on both classical and CD16+ monocytes assessed at Post and 1-h Post compared with Pre (P < 0.05 for all); 2) significantly lower LPS-stimulated TNF-α release in whole blood cultures at 1-h Post (P < 0.05 vs. Pre); and 3) significantly lower levels of plasma TNF-α at 1-h Post (P < 0.05 vs. Pre). There were no differences between T2D and HC, except for a larger decrease in plasma TNF-α in HC vs. T2D (group × time interaction, P < 0.05). One session of low-volume HIIT has immunomodulatory effects and provides potential anti-inflammatory benefits to people with, and without, T2D. PMID:28122717

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial.

PubMed

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Della Corte, Vittoriano; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-03-01

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

Systemic Inflammatory Load in Young and Old Ringdoves Is Modulated by Consumption of a Jerte Valley Cherry-Based Product

PubMed Central

Delgado, Jonathan; Terrón, María del Pilar; Garrido, María; Barriga, Carmen; Paredes, Sergio Damián; Espino, Javier

2012-01-01

Abstract A chronic subclinical inflammatory status that coexists with immune dysfunction is commonly found in the elderly population. Consumption of foods rich in antioxidants (e.g., cherries) is an attractive strategy to reduce risk from chronic diseases. Based on previous studies showing the antioxidant effect of a Jerte Valley cherry derivative product in humans, the objective of this work was to evaluate the effect of the intake of a Jerte Valley cherry-based beverage on inflammatory load in both young and old ringdoves (Streptopelia risoria). To this purpose, circulating levels of pro-inflammatory and anti-inflammatory cytokines as well as serum levels of different acute-phase proteins were measured before and after a 10-day treatment with the Jerte Valley cherry-based beverage. Thus, the 10-day treatment with the cherry-based beverage modulated the balance of pro- and anti-inflammatory cytokines in both young and old ringdoves by down-regulating the levels of pro-inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor-α, and interferon-γ) and up-regulating the levels of anti-inflammatory cytokines (IL-4, IL-2, and IL-10). Moreover, the 10-day treatment with the Jerte Valley cherry-based product reduced the levels of several proteins involved in acute-phase responses, such as C-reactive protein, haptoglobin, α2-macroglobulin, and serum amyloid P component. On the other hand, old birds showed imbalanced levels of inflammatory markers toward a pro-inflammatory status, thereby underlining the fact that aging is usually accompanied by systemic inflammation and inflammation-related chronic diseases. To sum up, the data suggest a potential health benefit by consuming the cherry-based beverage, especially in aged populations, through their anti-inflammatory properties. PMID:22846077

Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer.

PubMed

Schinagl, Alexander; Thiele, Michael; Douillard, Patrice; Völkel, Dirk; Kenner, Lukas; Kazemi, Zahra; Freissmuth, Michael; Scheiflinger, Friedrich; Kerschbaumer, Randolf J

2016-11-08

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer.

Attenuated fever in rats during late pregnancy is linked to suppressed interleukin-6 production after localized inflammation with turpentine.

PubMed

Aguilar-Valles, Argel; Poole, Stephen; Mistry, Yogesh; Williams, Sylvain; Luheshi, Giamal N

2007-08-15

An attenuated fever response to pathogens during late pregnancy is a phenomenon that has been described in several mammalian species, and although mechanisms are not completely understood, decreased prostaglandin E2 (PGE2) synthesis has been implicated. Upstream of PGE2, there is evidence to suggest that anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1ra) could play a significant role. In the present study we addressed the role of pro-inflammatory cytokines during late pregnancy, specifically interleukin-6 (IL-6), an important circulating mediator in fever. Turpentine oil (TURP), a very potent pyrogen and activator of IL-6, was injected into the hind-limb muscle of rats at the 18th day of pregnancy (GD 18) or in non-pregnant (NP) age-matched female controls. As expected, TURP injection induced a highly significant fever in the NP animals, which peaked 11 h post-injection and lasted for over 24 h. This was accompanied by a significant rise in circulating IL-6 levels, which correlated with changes in PGE2 synthesizing enzymes expression in the hypothalamus. In complete contrast, TURP-induced fever was totally absent in GD 18 animals whose body temperature did not deviate from basal values. The lack of response was additionally reflected by the absence of change in IL-6 concentration and by the significant attenuation of PGE2 synthesizing enzymes expression, which correlated with the suppressed expression of SOCS3, a hypothalamic marker of IL-6 activity. Contrary to the changes in circulating IL-6 levels at GD 18, IL-1ra was induced to levels comparable to those of NP females, suggesting that the influence of this anti-inflammatory cytokine on the fever response to TURP is at best minimal. These data further confirm the importance of IL-6 in fever generation and provide evidence that it may be a key component of the attenuated fever response in late pregnancy.

Attenuated fever in rats during late pregnancy is linked to suppressed interleukin-6 production after localized inflammation with turpentine

PubMed Central

Aguilar-Valles, Argel; Poole, Stephen; Mistry, Yogesh; Williams, Sylvain; Luheshi, Giamal N

2007-01-01

An attenuated fever response to pathogens during late pregnancy is a phenomenon that has been described in several mammalian species, and although mechanisms are not completely understood, decreased prostaglandin E2 (PGE2) synthesis has been implicated. Upstream of PGE2, there is evidence to suggest that anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1ra) could play a significant role. In the present study we addressed the role of pro-inflammatory cytokines during late pregnancy, specifically interleukin-6 (IL-6), an important circulating mediator in fever. Turpentine oil (TURP), a very potent pyrogen and activator of IL-6, was injected into the hind-limb muscle of rats at the 18th day of pregnancy (GD 18) or in non-pregnant (NP) age-matched female controls. As expected, TURP injection induced a highly significant fever in the NP animals, which peaked 11 h post-injection and lasted for over 24 h. This was accompanied by a significant rise in circulating IL-6 levels, which correlated with changes in PGE2 synthesizing enzymes expression in the hypothalamus. In complete contrast, TURP-induced fever was totally absent in GD 18 animals whose body temperature did not deviate from basal values. The lack of response was additionally reflected by the absence of change in IL-6 concentration and by the significant attenuation of PGE2 synthesizing enzymes expression, which correlated with the suppressed expression of SOCS3, a hypothalamic marker of IL-6 activity. Contrary to the changes in circulating IL-6 levels at GD 18, IL-1ra was induced to levels comparable to those of NP females, suggesting that the influence of this anti-inflammatory cytokine on the fever response to TURP is at best minimal. These data further confirm the importance of IL-6 in fever generation and provide evidence that it may be a key component of the attenuated fever response in late pregnancy. PMID:17556393

Oxidative Burst of Circulating Neutrophils Following Traumatic Brain Injury in Human

PubMed Central

Liao, Yiliu; Liu, Peng; Guo, Fangyuan; Zhang, Zhi-Yuan; Zhang, Zhiren

2013-01-01

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. PMID:23894384

Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG.

PubMed

Maggio, Marcello; Nicolini, Francesco; Cattabiani, Chiara; Beghi, Cesare; Gherli, Tiziano; Schwartz, Robert S; Valenti, Giorgio; Ceda, Gian Paolo

2012-07-01

Testosterone levels decrease with age. This decline is steeper during "critical illnesses". Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as "acute postoperative frailty". We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200 ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Measurement of Circulating Cytokines and Immune-Activation Markers by Multiplex Technology in the Clinical Setting: What Are We Really Measuring?

PubMed

Aziz, Najib

2015-01-01

Measurement of circulating cytokine levels can provide important information in the study of the pathogenesis of disease. John L. Fahey was a pioneer in the measurement of circulating cytokines and immune-activation markers and a leader in the quality assessment/control of assays for measurement of circulating cytokines. Insights into the measurement of circulating cytokines, including consideration of multiplex assays, are presented here.

Olive oil and leaf extract prevent fluoxetine-induced hepatotoxicity by attenuating oxidative stress, inflammation and apoptosis.

PubMed

Elgebaly, Hassan A; Mosa, Nermeen M; Allach, Mariam; El-Massry, Khaled F; El-Ghorab, Ahmed H; Al Hroob, Amir M; Mahmoud, Ayman M

2018-02-01

Olive oil and leaf extract have several health benefits; however, their beneficial effect against fluoxetine-induced liver injury has not been investigated. The present study aimed to scrutinize the impact of fluoxetine on the liver of rats and to evaluate the protective effects of olive oil and leaf extract. Rats received fluoxetine orally at dose of 10 mg/kg body weight for 7 consecutive days. The fluoxetine-induced rats were concurrently treated with olive oil or leaf extract. At the end of the experiment, blood and liver samples were collected for analysis. Fluoxetine administration significantly increased circulating ALT, AST, ALP and the pro-inflammatory cytokines TNF-α and IL-1β levels in rats. Histological analysis showed several alterations, such as inflammatory cells infiltration, hepatocyte vacuolation and dilated sinusoids in the liver of fluoxetine-induced rats. Concurrent supplementation of olive oil and olive leaf extract significantly reduced circulating liver function marker enzymes and pro-inflammatory cytokines, and prevented fluoxetine-induced histological alterations. Both olive oil and leaf extract significantly decreased liver lipid peroxidation and nitric oxide, and ameliorated liver glutathione, superoxide dismutase, catalase and glutathione peroxidase. In addition, olive oil and leaf extract prevented fluoxetine-induced apoptosis in the liver of rats as evidenced by decreased expression of Bax and caspase-3, and up-regulated expression of Bcl-2. In conclusion, olive oil and leaf extract protect against fluoxetine-induced liver injury in rats through attenuation of oxidative stress, inflammation and apoptosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Quantifying oral inflammatory load: oral neutrophil counts in periodontal health and disease.

PubMed

Landzberg, M; Doering, H; Aboodi, G M; Tenenbaum, H C; Glogauer, M

2015-06-01

Neutrophils are the primary white blood cells that are recruited to fight the initial phases of microbial infections. While healthy norms have been determined for circulating blood neutrophil counts in order to identify patients with suspected systemic infections, the levels of oral neutrophils (oPMNs) in oral health and in the presence of periodontal diseases have not been described. It is important to address this deficiency in our knowledge as neutrophils are the primary immune cell present in the crevicular fluid and oral environment and previous work has suggested that they may be good indicators of overall oral inflammation and periodontal disease severity. The objective of this study was to measure oPMN counts obtained in a standardized oral rinse from healthy patients and from those with chronic periodontal disease in order to determine if oPMN levels have clinical relevance as markers of periodontal inflammation. A parallel goal of this investigation was to introduce the concept of 'oral inflammatory load', which constitutes the inflammatory burden experienced by the body as a consequence of oral inflammatory disease. Periodontal examinations of patients with a healthy periodontium and chronic periodontal disease were performed (n = 124). Two standardized consecutive saline rinses of 30 s each were collected before patient examination and instrumentation. Neutrophils were quantified in the rinse samples and correlated with the clinical parameters and periodontal diagnosis. Average oPMN counts were determined for healthy patients and for those with mild, moderate and severe chronic periodontal diseases. A statistically significant correlation was found between oPMN counts and deep periodontal probing, sites with bleeding on probing and overall severity of periodontal disease. oPMN counts obtained through a 30-s oral rinse are a good marker of oral inflammatory load and correlate with measures of periodontal disease severity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Glycoxidation and inflammatory markers in patients on treatment with PMMA-based protein-leaking dialyzers.

PubMed

Galli, Francesco; Benedetti, Serena; Floridi, Ardesio; Canestrari, Franco; Piroddi, Marta; Buoncristiani, Emanuela; Buoncristiani, Umberto

2005-02-01

High-molecular-weight solutes such as glycation and oxidation protein products are putative proinflammatory mediators found in the uremic blood. The elimination of these and other large solutes by protein-leaking dialyzers (PLD) might help to correct the inflammatory status of maintenance hemodialysis (HD) patients. Two matched groups of 13 standard 3 times/week HD patients were treated for 6 months with PMMA-based PLD and non-protein-leaking dialyzers (NPLD), respectively. At baseline, 1, 3, and 6 months, we measured the blood levels of the inflammatory cytokines IL-1beta, TNF-alpha, IL-6, the acute-phase protein C-reactive protein (CRP), the adhesion molecules ICAM-1, VCAM-1, and selectine-E, the chemotaxis factors MCP-1, and the glycation and oxidation protein end products pentosidine, protein carbonyls, and AOPP. In all the patients at baseline, pre-HD levels of glycation and oxidation protein markers, and inflammatory parameters were significantly higher than in healthy control subjects (P < 0.01 or greater). After 6 months, in the group on treatment with PLD, but not in that on NPLD, there was a significant decrease (P < 0.05 or greater) of pre-HD values of total pentosidine (mainly represented by pentosidine in serum albumin; -43%), protein carbonyls (-42%), AOPP (-38%), and the inflammatory cytokines IL-1beta (-49%), IL-6 (-39%), and TNF-alpha (-20%), while IL-10 and INF-gamma increased by 67% and 37%, respectively. Proinflammatory cytokines, and particularly IL-6, showed a positive correlation with the levels of circulating pentosidine. Protidemia was not significantly modified at the end of the study in both the groups. The results in this pilot study show that the removal of large solutes by PLD can improve some indices of chronic inflammation in HD patients. Further studies are required to determine the relevance of the individual solutes removed with PLD as proinflammatory mediators in the uremic environment.

State of the Art: Blood Biomarkers for Risk Stratification in Patients with Stable Ischemic Heart Disease.

PubMed

Omland, Torbjørn; White, Harvey D

2017-01-01

Multiple circulating biomarkers have been associated with the incidence of cardiovascular events and proposed as potential tools for risk stratification in stable ischemic heart disease (IHD), yet current guidelines do not make any firm recommendations concerning the use of biomarkers for risk stratification in this setting. This state-of-the-art review provides an overview of biomarkers for risk stratification in stable IHD. Circulating biomarkers associated with the risk of cardiovascular events in patients with stable IHD reflect different pathophysiological processes, including myocardial injury, myocardial stress and remodeling, metabolic status, vascular inflammation, and oxidative stress. Compared to the primary prevention setting, biomarkers reflecting end-organ damage and future risk of heart failure development and cardiovascular death may play more important roles in the stable IHD setting. Accordingly, biomarkers that reflect chronic, low-grade myocardial injury, and stress, i.e., high-sensitivity cardiac troponins and natriuretic peptides, provide graded and incremental prognostic information to conventional risk markers. In contrast, in stable IHD patients the prognostic value of traditional metabolic biomarkers, including serum lipids, is limited. Among several novel biomarkers, growth-differentiation factor-15 may provide the most robust prognostic information, whereas most inflammatory markers provide limited incremental prognostic information to risk factor models that include conventional risk factors, natriuretic peptides, and high-sensitivity troponins. Circulating biomarkers hold promise as useful tools for risk stratification in stable IHD, but their future incorporation into clinically useful risk scores will depend on prospective, rigorously performed clinical trials that document enhanced risk prediction. © 2016 American Association for Clinical Chemistry.

The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

PubMed Central

Antonelli, Lis R. V.; Leoratti, Fabiana M. S.; Costa, Pedro A. C.; Rocha, Bruno C.; Diniz, Suelen Q.; Tada, Mauro S.; Pereira, Dhelio B.; Teixeira-Carvalho, Andrea; Golenbock, Douglas T.; Gonçalves, Ricardo; Gazzinelli, Ricardo T.

2014-01-01

Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax–infected patients display significant increase in circulating monocytes, which were defined as CD14+CD16− (classical), CD14+CD16+ (inflammatory), and CD14loCD16+ (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16+ cells, in particular the CD14+CD16+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14+CD16+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14+CD16+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.

PubMed

Calder, P C; Ahluwalia, N; Albers, R; Bosco, N; Bourdet-Sicard, R; Haller, D; Holgate, S T; Jönsson, L S; Latulippe, M E; Marcos, A; Moreines, J; M'Rini, C; Müller, M; Pawelec, G; van Neerven, R J J; Watzl, B; Zhao, J

2013-01-01

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

The Effect of Pressure-Controlled Ventilation and Volume-Controlled Ventilation in Prone Position on Pulmonary Mechanics and Inflammatory Markers.

PubMed

Şenay, Hasan; Sıvacı, Remziye; Kokulu, Serdar; Koca, Buğra; Bakı, Elif Doğan; Ela, Yüksel

2016-08-01

The aim of this present study is to compare the effect of pressure-controlled ventilation and volume-controlled ventilation on pulmonary mechanics and inflammatory markers in prone position. The study included 41 patients undergoing to vertebrae surgery. The patients were randomized into two groups: Group 1 received volume-controlled ventilation, while group 2 received pressure-controlled ventilation. The demographic data, pulmonary mechanics, the inflammatory marker levels just after the induction of anesthetics, at the 6th and 12th hours, and gas analysis from arterial blood samples taken at the beginning and the 30th minute were recorded. The inflammatory marker levels increased in both groups, without any significant difference among groups. Peak inspiratory pressure level was higher in the volume-controlled ventilation group. This study revealed that there is no difference regarding inflammatory marker levels between volume- and pressure-controlled ventilation.

Inflamm-aging does not simply reflect increases in pro-inflammatory markers.

PubMed

Morrisette-Thomas, Vincent; Cohen, Alan A; Fülöp, Tamàs; Riesco, Éléonor; Legault, Véronique; Li, Qing; Milot, Emmanuel; Dusseault-Bélanger, Françis; Ferrucci, Luigi

2014-07-01

Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflicting results due to complex interactions among the markers. A multidimensional approach allows a more robust interpretation of the various relationships between the markers. We applied principal component analysis (PCA) to 19 inflammatory biomarkers from the InCHIANTI study. We identified a clear, stable structure among the markers, with the first axis explaining inflammatory activation (both pro- and anti-inflammatory markers loaded strongly and positively) and the second axis innate immune response. The first but not the second axis was strongly correlated with age (r=0.56, p<0.0001, r=0.08 p=0.053), and both were strongly predictive of mortality (hazard ratios per PCA unit (95% CI): 1.33 (1.16-1.53) and 0.87 (0.76-0.98) respectively) and multiple chronic diseases, but in opposite directions. Both axes were more predictive than any individual markers for baseline chronic diseases and mortality. These results show that PCA can uncover a novel biological structure in the relationships among inflammatory markers, and that key axes of this structure play important roles in chronic disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The expression of inflammatory cytokines, TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity.

PubMed

Filkor, Kata; Németh, Tibor; Nagy, István; Kondorosi, Éva; Urbán, Edit; Kemény, Lajos; Szolnoky, Győző

2016-08-01

The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro- and anti-inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non-responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non-responders. Circulating blood mononuclear cells of patients overexpress pro-inflammatory (IL-1α, TNFα, CXCL-8) and anti-inflammatory (IL-10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL-1α is notably overexpressed in venous leg ulcer treatment non-responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms.

PubMed

You, Tongjian; Arsenis, Nicole C; Disanzo, Beth L; Lamonte, Michael J

2013-04-01

Chronic, systemic inflammation is an independent risk factor for several major clinical diseases. In obesity, circulating levels of inflammatory markers are elevated, possibly due to increased production of pro-inflammatory cytokines from several tissues/cells, including macrophages within adipose tissue, vascular endothelial cells and peripheral blood mononuclear cells. Recent evidence supports that adipose tissue hypoxia may be an important mechanism through which enlarged adipose tissue elicits local tissue inflammation and further contributes to systemic inflammation. Current evidence supports that exercise training, such as aerobic and resistance exercise, reduces chronic inflammation, especially in obese individuals with high levels of inflammatory biomarkers undergoing a longer-term intervention. Several studies have reported that this effect is independent of the exercise-induced weight loss. There are several mechanisms through which exercise training reduces chronic inflammation, including its effect on muscle tissue to generate muscle-derived, anti-inflammatory 'myokine', its effect on adipose tissue to improve hypoxia and reduce local adipose tissue inflammation, its effect on endothelial cells to reduce leukocyte adhesion and cytokine production systemically, and its effect on the immune system to lower the number of pro-inflammatory cells and reduce pro-inflammatory cytokine production per cell. Of these potential mechanisms, the effect of exercise training on adipose tissue oxygenation is worth further investigation, as it is very likely that exercise training stimulates adipose tissue angiogenesis and increases blood flow, thereby reducing hypoxia and the associated chronic inflammation in adipose tissue of obese individuals.

Obstructive sleep apnea as an independent stroke risk factor: possible mechanisms.

PubMed

Godoy, Jaime; Mellado, Patricio; Tapia, Jorge; Santín, Julia

2009-03-01

Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD. The mechanisms involved in this relation are most likely induced by the periodic hypoxia/reoxygenation that characteristically occurs in OSA, which results in oxidative stress, endothelial dysfunction and activation of the inflammatory cascade, all of which favor atherogenesis. Numerous markers of these changes have been reported in OSA patients, including increased circulating free radicals, increased lipid peroxidation, decreased antioxidant capacity, elevation of tumor necrosis factor and interleukines, increased levels of proinflammatory nuclear transcription factor kappa B, decreased circulating nitric oxide, elevation of vascular adhesion molecules and vascular endothelial growth factor. In addition, several authors have described that Continuous Positive Airway Pressure, the standard OSA therapy, reverts these abnormalities. Further research is needed in order to better clarify the complex mechanisms that underlie the relation between OSA, atherogenesis and CVD which most likely will have significant clinical impact.

Metabolic endotoxaemia--a potential novel link between ovarian inflammation and impaired progesterone production.

PubMed

Tremellen, Kelton; Syedi, Naeema; Tan, Sze; Pearce, Karma

2015-04-01

Medical conditions such as obesity and inflammatory bowel disease are associated with impaired luteal function, menstrual disturbance and infertility. It is proposed that the disturbance in gut wall integrity ("leaky gut") seen in these conditions may result in the passage of bacterial endotoxin (LPS) from the colonic lumen into the circulation that may initiate inflammation in the ovary and subsequently impair hormone production. Quantify the association between systemic levels of LBP, a marker of endotoxin exposure, and levels of inflammation in the ovary (follicular fluid IL-6), plus steroid hormone production in 45 women undergoing IVF treatment. Endotoxaemia (LBP) were positively correlated with plasma CRP and inflammation within the ovary (follicular fluid IL-6). Furthermore, endotoxaemia was negatively correlated with progesterone production. The observed correlations, together with previously published animal studies linking endotoxin exposure to impaired luteal function, suggest that the translocation of bacterial endotoxin from the gut lumen into the circulation has the potential to interfere with progesterone production and result in luteal deficiency.

Inflammation in Polycystic Ovary Syndrome: Underpinning of insulin resistance and ovarian dysfunction

PubMed Central

González, Frank

2012-01-01

Chronic low-grade inflammation has emerged as a key contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). A dietary trigger such as glucose is capable of inciting oxidative stress and an inflammatory response from mononuclear cells (MNC) of women with PCOS, and this phenomenon is independent of obesity. This is important because MNC-derived macrophages are the primary source of cytokine production in excess adipose tissue, and also promote adipocyte cytokine production in a paracrine fashion. The proinflammatory cytokine tumor necrosis factor-α (TNFα) is a known mediator of insulin resistance. Glucose-stimulated TNFα release from MNC along with molecular markers of inflammation are associated with insulin resistance in PCOS. Hyperandrogenism is capable of activating MNC in the fasting state, thereby increasing MNC sensitivity to glucose; and this may be a potential mechanism for promoting diet-induced inflammation in PCOS. Increased abdominal adiposity is prevalent across all weight classes in PCOS, and this inflamed adipose tissue contributes to the inflammatory load in the disorder. Nevertheless, glucose ingestion incites oxidative stress in normal weight women with PCOS even in the absence of increased abdominal adiposity. In PCOS, markers of oxidative stress and inflammation are highly correlated with circulating androgens. Chronic suppression of ovarian androgen production does not ameliorate inflammation in normal weight women with the disorder. Furthermore, in vitro studies have demonstrated the ability of pro-inflammatory stimuli to upregulate the ovarian theca cell steroidogenic enzyme responsible for androgen production. These findings support the contention that inflammation directly stimulates the polycystic ovary to produce androgens. PMID:22178787

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome.

PubMed

Lucero, Diego; Zago, Valeria; López, Graciela I; Graffigna, Mabel; Fainboim, Hugo; Miksztowicz, Verónica; Meroño, Tomás; Belli, Susana; Levalle, Oscar; Wikinski, Regina; Brites, Fernando; Berg, Gabriela; Schreier, Laura

2011-01-14

It is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics. Seventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured. HS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = -0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = -0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic. Simple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition. Copyright © 2010 Elsevier B.V. All rights reserved.

Helichrysum and Grapefruit Extracts Boost Weight Loss in Overweight Rats Reducing Inflammation.

PubMed

de la Garza, Ana Laura; Etxeberria, Usune; Haslberger, Alexander; Aumueller, Eva; Martínez, J Alfredo; Milagro, Fermín I

2015-08-01

Obesity is characterized by an increased production of inflammatory markers. High levels of circulating free fatty acids and chronic inflammation lead to increased oxidative stress, contributing to the development of insulin resistance (IR). Recent studies have focused on the potential use of flavonoids for obesity management due to their antioxidant and anti-inflammatory properties. This study was designed to investigate the antioxidant and anti-inflammatory effects of helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty-eight male Wistar rats were randomly distributed in two groups: control group (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water and food access, the rats fed HFS diet changed to standard diet and were reassigned into three groups (n=10 each group): nonsupplemented, helichrysum extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks. Rats supplemented with both extracts gained less body weight during the 5-week period of treatment, showed lower serum insulin levels and liver TBARS levels. Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract-administered groups. These results were accompanied by a reduction in TNFα gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2 expression in intestinal mucosa. Helichrysum and grapefruit extracts might be used as complement hypocaloric diets in weight loss treatment. Both extracts helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant rats.

Clinical study of the hypothesis of endogenous collateral wind on acute coronary syndrome: a review.

PubMed

Wang, Xian; Zhang, Cong; Yang, Ran; Zhu, Haiyan; Zhao, Huaibing; Li, Xiaoming

2014-01-01

Acute Coronary Syndrome (ACS), is a serious threat to people's health, and life, and in recent years, the incidence has increased yearly. This study was to propose the hypothesis of "endogenous collateral wind" based on the patho-mechanism of thrombogenesis complicated by ruptured plaque on ACS, and the theory of traditional Chinese medicine. Through successful coronary angiography (CAG), and intravascular ultrasound (IVUS), patients with coronary artery disease were made the differential diagnosis such as blood stasis, blood stasis due to phlegm obstruction, and endogenous collateral wind. The levels of plasma inflammatory marker were measured to study on the characteristics of "endogenous collateral wind". Luo heng dripping pills with promoting blood circulation to expel wind-evil, and remove wetness were made based on the hypothesis of "endogenous collateral wind" on ACS. Patients with unstable angina were randomly divided into 3, groups based on therapeutic methods: conventional therapy group, Luo Heng dripping pills group and Tongxinluo caps. Differences among groups were compared. There were great changes in number and degree of coronary arteriostenosis confirmed by CAG, the types of ACC/AHA lesion and Levin lesion confirmed by CAG, remodeling index, positive or negative remodeling percentage measured by IVUS, the plasma levels of plasma inflammatory marker measured by ELLSA in the patients with endogenous collateral wind, compared with patients with blood stasis and blood stasis due to phlegm obstruction. The total effective rate of improved angina in Luo Heng dripping pills group was significantly higher than those in other two groups. The levels of plasma inflammatory marker were significantly lower in Luo Heng dripping pills group. There were some pathological basis which were found about the hypothesis of "endogenous collateral wind" on acute coronary syndrome. It provided evidences for patients with coronary artery disease treated by medicines with expelling evil-wind, and removing wetness.

Effect of DHA on plasma fatty acid availability and oxidative stress during training season and football exercise.

PubMed

Martorell, Miquel; Capó, Xavier; Sureda, Antoni; Batle, Joan M; Llompart, Isabel; Argelich, Emma; Tur, Josep A; Pons, Antoni

2014-08-01

The aim was to determine the effects of a diet supplemented with 1.14 g per day of docosahexaenoic acid (DHA) for eight weeks on the plasma oxidative balance and anti-inflammatory markers after training and acute exercise. Fifteen volunteer male football players were randomly assigned to placebo or experimental and supplemented groups. Blood samples were taken under resting conditions at the beginning and after eight weeks of training under resting and post-exercise conditions. The experimental beverage increased the plasma DHA availability in non-esterified fatty acids (NEFAs) and triglyceride fatty acids (TGFAs) and increased the polyunsaturated fatty acid (PUFA) fraction of NEFAs but had no effects on the biomarkers for oxidative balance in plasma. During training, plasma protein markers of oxidative damage, the haemolysis degree and the antioxidant enzyme activities increased, but did not affect lipid oxidative damage. Training season and DHA influenced the circulating levels of prostaglandin E2 (PGE2). Acute exercise did not alter the basal levels of plasma markers for oxidative and nitrosative damage of proteins and lipids, and the antioxidant enzyme activities, although DHA-diet supplementation significantly increased the PGE2 in plasma after acute exercise. In conclusion, the training season and acute exercise, but not the DHA diet supplementation, altered the pattern of plasma oxidative damage, as the antioxidant system proved sufficient to prevent the oxidative damage induced by the acute exercise in well-trained footballers. The DHA-diet supplementation increased the prostaglandin PGE2 plasma evidencing anti-inflammatory effects of DHA to control inflammation after acute exercise.

Circulating levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α and risk of colorectal adenomas: a meta-analysis.

PubMed

Zhang, Xiaoqian; Liu, Shanglong; Zhou, Yanbing

2016-09-27

Results from publications on inflammatory markers of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and risk of colorectal adenomas are not consistent. A meta-analysis was conducted to explore the above-mentioned associations. Relevant studies were identified by a search of Embase, Medline and PubMed through February 2016. A random effect model was adopted to combine study-specific odds ratio (OR) and 95% confidence interval (95% CI). Between-study heterogeneity and publications bias were assessed. Dose-response relationships were assessed by restricted cubic splines. Nineteen observational studies were included. For highest vs. lowest levels, results from this meta-analysis did not support an association between circulating levels of CRP [OR (95% CI): 1.15 (0.94-1.40)], IL-6 [1.17 (0.94-1.46)] and TNF-α [0.99 (0.75-1.31)] and risk of colorectal adenomas, respectively. The findings were supported by sensitivity analysis and subgroup analysis. In dose-response analysis, the risk of colorectal adenomas increased by 2% [1.02 (0.97-1.08)] for each 1 mg/L increment in circulation CRP levels, 9% [1.09 (0.91-1.31)] for each 1 ng/L increment in circulation IL-6 levels, and 6% [1.06 (0.93-1.21)] for each 1 pg/mL increment in circulation TNF-α levels. Moderate between-study heterogeneity was found. No evidence of publication bias was found. Circulation levels of CRP, IL-6 and TNF-α might be not useful biomarkers for identifying colorectal adenomas, respectively.

Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Izaguirre, Maitane; Hernández-Lizoain, José Luis; Baixauli, Jorge; Martí, Pablo; Valentí, Víctor; Moncada, Rafael; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

2016-01-01

Background Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. Methods Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA. Results Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected. Conclusions To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics. PMID:27612200

Fever of unknown origin in the elderly.

PubMed

Wakefield, K M; Henderson, S T; Streit, J G

1989-06-01

Fever is a prominent sign of an acute-phase response induced by microbial invasion, tissue injury, immunologic reactions, or inflammatory processes. This generalized host response is produced by a multiplicity of localized or systemic diseases and characterized by acute, subacute, or chronic changes in metabolic, endocrinologic, neurologic, and immunologic functions. The fundamental event is an initiation of the acute-phase response by the production of a mediated molecule called IL-1. This polypeptide is produced primarily from phagocytic cells such as blood monocytes, phagocytic lining cells of the liver and spleen, and other tissue macrophages. IL-1 produces a local reaction but also enters the circulation, acting as a hormone to mediate distant organ system responses to infection, immunologic reaction, and inflammatory processes. Fever is the result when IL-1 initiates the synthesis of prostaglandins, notably prostaglandin E2 in the thermoregulatory center located in the anterior hypothalamus. The thermostatic set point is then raised and mechanisms to conserve heat (vasoconstriction) and to produce heat (shivering) are initiated. The result is a sudden rise in body temperature. The same basic mechanisms are involved in FUO. Many of the biologic and biochemical changes that are seen in FUO are also evidence of an acute-phase response. The elevated erythrocyte sedimentation rate is partly due to increased synthesis of hepatic proteins, including compliment components, ceruloplasmin, fibrinogen, and C-reactive protein. IL-1 acts directly on the bone marrow to increase absolute numbers and immaturity of circulating neutrophils. Anemia is produced by many mechanisms, including the reduction of circulating serum iron. Although fever production in the elderly maybe delayed or of less intensity, it is still a marker of significant disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Inflammatory markers following acute fuel oil exposure or bacterial lipopolysaccharide in mallard ducks (Anas platyrhynchos).

PubMed

Lee, Kelly A; Tell, Lisa A; Mohr, F Charles

2012-12-01

Adult mallard ducks (Anas platyrhynchos) were orally dosed with bunker C fuel oil for 5 days, and five different inflammatory markers (haptoglobin, mannan-binding lectin, ceruloplasmin, unsaturated iron-binding capacity, and plasma iron) were measured in blood plasma prior to and 8, 24, 48, and 72 hr following exposure. In order to contrast the response to fuel oil with that of a systemic inflammatory response, an additional five ducks were injected intramuscularly with bacterial lipopolysaccharide (LPS). Oil-treated birds had an inflammatory marker profile that was significantly different from control and LPS-treated birds, showing decreases in mannan-binding lectin-dependent hemolysis and unsaturated iron-binding capacity, but no changes in any of the other inflammatory markers. Birds treated with oil also exhibited increased liver weights, decreased body and splenic weights, and decreased packed cell volume.

Inflammatory Markers and Plasma Lipids in HIV Patients: A Correlation Analysis Study

PubMed Central

Muswe, Rudo; Oktedalen, Olav; Zhou, Danai T.; Zinyando, Enita; Shawarira-Bote, Sandra; Stray-Pedersen, Babill; Siziba, Atipa; Gomo, Zvenyika A.R.

2017-01-01

Background: Recent evidence suggests that HIV infection, even with treatment, increases the risk of coronary heart disease (CHD) and that both chronic inflammation and traditional risk factors play key roles in HIV-associated CHD. Subjects and Methods: Patients (N=152), attending Harare HIV clinic, 26% of them male and 82% of them on antiretroviral therapy (ART), were studied. Inflammatory markers comprising of cytokines such as pro-inflammatory tumor necrosis factor-α, (TNF-α), anti-inflammatory interleukin 10, (IL-10) and highly sensitive C reactive protein (hsCRP) together with lipids were assayed using enzyme linked immunosorbent assay (ELISA), immuno-turbidimetric and enzymatic assays, respectively. Correlation analysis of inflammatory markers versus lipid profiles was carried out using bivariate regression analysis. Results: Anti-inflammatory cytokine IL-10 and inflammatory hsCRP levels were elevated when measured in all the HIV positive patients, while TNF-α and lipid levels were within normal ranges. Pro-inflammatory TNF-α was significantly higher in ART-naive patients than ART-experienced patients, whereas the reverse was observed for anti-inflammatory IL-10 and anti-atherogenic HDL-C. Correlation analysis indicated a significant positive linear association between IL-10 and total cholesterol (TC) levels but no other correlations were found. Conclusion: High cytokine ratio (TNF-α/IL-10) indicates higher CHD risk in ART-naive patients compared to the ART-exposed. The CHD risk could be further strengthened by interplay between inflammatory markers and high prevalence of low HDL-C. Lack of correlation between pro-inflammatory markers (hsCRP and TNF-α) with lipid fractions and correlation between anti-inflammatory IL-10 with artherogenic TC were unexpected findings, necessitating further studies in future. PMID:29387269

Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation

PubMed Central

Oliveira, Marina G.; Mesquita, Eliene D. D.; Silva, Elisangela; Rauwerdink, Anneloek; Cobelens, Frank; Oliveira, Martha M.; Kritski, Afrânio

2017-01-01

Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Methods Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested. Results Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. Conclusions CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. PMID:28384354

Relationship between insulin resistance, hs-CRP, and body fat and serum osteoprotegerin/RANKL in prediabetic patients.

PubMed

Bilgir, Oktay; Yavuz, Mehmet; Bilgir, Ferda; Akan, Ozden Y; Bayindir, Aslı G; Calan, Mehmet; Bozkaya, Giray; Yuksel, Arif

2018-03-01

Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPN) are soluble members of the tumor necrosis factor superfamily. Growing evidence suggest that there is link between inflammation, insulin resistance and OPG, soluble RANKL (sRANKL). We aimed to ascertain whether OPG and sRANKL levels are altered in prediabetic subjects and there is association between OPG/sRANKL and metabolic parameters. Forty prediabetic subjects and 40 age- and BMI-matched controls were recruited for this cross-sectional study. Circulating OPG, sRANKL were measured using ELISA. Anthropometric and metabolic parameters were also determined. Circulating sRANKL (97.74±17.67 vs. 55.00±11.19 pg/mL, P=0.010) and OPG (261.54±74.55 vs. 159.23±52.91 pg/mL, P=0.020) levels were found to be significantly higher in diabetic subjects compared with control subjects. There was a positive correlation between sRANKL and OPG. sRANKL also positively correlated with BMI, insulin resistance marker HOMA-IR, inflammatory marker hs-CRP. Logistic regression analyses revealed that the odds ratio was increased for prediabetes in subjects with having elevated sRANKL levels. Increased sRANKL and OPG levels were associated with prediabetic subjects. sRANKL and OPG may play a role in the pathogenesis of diabetes as well as metabolic disturbance.

Association of Inflammatory, Lipid, and Mineral Markers with Cardiac Calcification in Older Adults

PubMed Central

Bortnick, Anna E.; Bartz, Traci M.; Ix, Joachim H.; Chonchol, Michel; Reiner, Alexander; Cushman, Mary; Owens, David; Barasch, Eddy; Siscovick, David S.; Gottdiener, John S.; Kizer, Jorge R.

2016-01-01

Objective Calcification of the aortic valve and adjacent structures involves inflammatory, lipid, and mineral metabolism pathways. We hypothesized that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. Methods We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate, or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein [Lp] (a), lipoprotein-associated phospholipase A2 [LpPLA2] mass and activity), inflammatory (interleukin-6, soluble [s] CD14), and mineral metabolism (fetuin-A, fibroblast growth factor [FGF]-23) that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcium (AVC), aortic annular calcium (AAC) and mitral annular calcium (MAC) were assessed with relative risk (RR) regression. Results Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA2 mass and activity, and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were: Lp(a), 1.051 (1.022–1.081); LpPLA2 mass, 1.036 (1.006–1.066), and activity, 1.037 (1.004–1.071); sCD14, 1.039 (1.005–1.073). FGF-23 was positively associated with MAC, 1.040 (1.004–1.078), and fetuin-A was negatively associated, 0.949 (0.911–0.989). No biomarkers were significantly associated with AAC. Conclusions This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of lipoprotein and inflammatory pathways may provide added insight into the etiology AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC. PMID:27411840

A peripheral immune response to remembering trauma contributes to the maintenance of fear memory in mice.

PubMed

Young, Matthew B; Howell, Leonard L; Hopkins, Lauren; Moshfegh, Cassandra; Yu, Zhe; Clubb, Lauren; Seidenberg, Jessica; Park, Jeanie; Swiercz, Adam P; Marvar, Paul J

2018-05-17

Alterations in peripheral immune markers are observed in individuals with post-traumatic stress disorder (PTSD). PTSD is characterized in part by impaired extinction of fear memory for a traumatic experience. We hypothesized that fear memory extinction is regulated by immune signaling stimulated when fear memory is retrieved. The relationship between fear memory and the peripheral immune response was tested using auditory Pavlovian fear conditioning in mice. Memory for the association was quantified by the amount of conditioned freezing exhibited in response to the conditioned stimulus (CS), extinction and time-dependent changes in circulating inflammatory cytokines. Brief extinction training with 12 CS rapidly and acutely increased circulating levels of the cytokine interleukin-6 (IL-6), downstream IL-6 signaling, other IL-6 related pro-inflammatory cytokines. Transgenic manipulations or neutralizing antibodies that inhibit IL-6 activity did not affect conditioned freezing during the acquisition of fear conditioning or extinction but significantly reduced conditioned freezing 24 h after extinction training with 12 CS. Conversely, conditioned freezing after extinction training was unchanged by IL-6 inhibition when 40 CS were used during the extinction training session. In addition to effectively diminishing conditioned freezing, extinction training with 40 CS also diminished the subsequent IL-6 response to the CS. These data demonstrate that IL-6 released following fear memory retrieval contributes to the maintenance of that fear memory and that this effect is extinction dependent. These findings extend the current understanding for the role of the immune system in PTSD and suggest that IL-6 and other IL-6 related pro-inflammatory cytokines may contribute to the persistence of fear memory in PTSD where fear memory extinction is impaired. Copyright © 2018 Elsevier Ltd. All rights reserved.

The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels.

PubMed

Kumar, Anand; Haery, Cameron; Paladugu, Bhanu; Kumar, Aseem; Symeoneides, Simon; Taiberg, Leo; Osman, Jailan; Trenholme, Gordon; Opal, Steven M; Goldfarb, Roy; Parrillo, Joseph E

2006-01-15

This study was designed to examine the relationship between the timing of antibiotic treatment and both survival rates and hemodynamic/inflammatory correlates of survival in a murine model of Escherichia coli septic shock. Surgical implantation of an E. coli (O18:K1:H7)-laced, gelatin capsule-encased fibrinogen clot was used to generate a bacteremic model of murine septic shock. Survival duration, hemodynamic responses, and circulating serum tumor necrosis factor (TNF)-alpha , interleukin (IL)-6, and lactate levels were assessed in relation to increasing delays in or absence of antibiotic treatment. A critical inflection point with respect to survival occurred between 12 and 15 h after implantation. When initiated at or before 12 h, antibiotic treatment resulted in < or = 20% mortality, but, when initiated at or after 15 h, it resulted in >85% mortality. Physiologically relevant hypotension developed in untreated septic mice by 12 h after implantation. Values for heart rate differed between untreated septic mice and sham-infected control mice by 6 h after implantation, whereas values for cardiac output and stroke volume did not differ until at least 18-24 h after implantation. Antibiotic treatment initiated > or = 12 h after implantation was associated with persistence of increased circulating serum lactate, TNF- alpha , and IL-6 levels. The timing of antibiotic treatment relative to hypotension is closely associated with survival in this murine model of septic shock. Delay in antibiotic treatment results in the persistence of inflammatory/stress markers even after antibiotic treatment is initiated.

S100A8/A9 increases the mobilization of pro-inflammatory Ly6Chigh monocytes to the synovium during experimental osteoarthritis.

PubMed

Cremers, Niels A J; van den Bosch, Martijn H J; van Dalen, Stephanie; Di Ceglie, Irene; Ascone, Giuliana; van de Loo, Fons; Koenders, Marije; van der Kraan, Peter; Sloetjes, Annet; Vogl, Thomas; Roth, Johannes; Geven, Edwin J W; Blom, Arjen B; van Lent, Peter L E M

2017-09-29

Monocytes are dominant cells present within the inflamed synovium during osteoarthritis (OA). In mice, two functionally distinct monocyte subsets are described: pro-inflammatory Ly6C high and patrolling Ly6C low monocytes. Alarmins S100A8/A9 locally released by the synovium during inflammatory OA for prolonged periods may be dominant proteins involved in stimulating recruitment of Ly6C high monocytes from the circulation to the joint. Our objective was to investigate the role of S100A8/A9 in the mobilization of Ly6C high and Ly6C low monocytic populations to the inflamed joint in collagenase-induced OA (CiOA). S100A8 was injected intra-articularly to investigate monocyte influx. CiOA was induced by injection of collagenase into knee joints of wild-type C57BL/6 (WT), and S100a9 -/- mice. Mice were sacrificed together with age-matched saline-injected control mice (n = 6/group), and expression of monocyte markers, pro-inflammatory cytokines, and chemokines was determined in the synovium using ELISA and RT-qPCR. Cells were isolated from the bone marrow (BM), spleen, blood, and synovium and monocytes were identified using FACS. S100A8/A9 was highly expressed during CiOA. Intra-articular injection of S100A8 leads to elevated expression of monocyte markers and the monocyte-attracting chemokines CCL2 and CX3CL1 in the synovium. At day 7 (d7) after CiOA induction in WT mice, numbers of Ly6C high , but not Ly6C low monocytes, were strongly increased (7.6-fold) in the synovium compared to saline-injected controls. This coincided with strong upregulation of CCL2, which preferentially attracts Ly6C high monocytes. In contrast, S100a9 -/- mice showed a significant increase in Ly6C low monocytes (twofold) within the synovium at CiOA d7, whereas the number of Ly6C high monocytes remained unaffected. In agreement with this finding, the Ly6C low mobilization marker CX3CL1 was significantly higher within the synovium of S100a9 -/- mice. Next, we studied the effect of S100A8/A9 on release of Ly6C high monocytes from the BM into the circulation. A 14% decrease in myeloid cells was found in WT BM at CiOA d7. No decrease in myeloid cells in S100a9 -/- BM was found, suggesting that S100A8/A9 promotes the release of myeloid populations from the BM. Induction of OA locally leads to strongly elevated S100A8/A9 expression and an elevated influx of Ly6C high monocytes from the BM to the synovium.

Circulating levels of FAS/APO-1 in patients with the systemic inflammatory response syndrome.

PubMed

Torre, Donato; Tambini, Roberto; Manfredi, Mariangela; Mangani, Valerio; Livi, Paola; Maldifassi, Viviana; Campi, Paolo; Speranza, Filippo

2003-04-01

Resolution of inflammation/infection involves removal of neutrophils and other inflammatory cells by the induction of apoptosis. Fas/Apo-1 is a widely occurring apoptotic signal receptor molecule expressed by almost any type of cell, which is also released in a soluble circulating form. In this study we investigated the role of circulating Fas/Apo-1 in patients with systemic inflammatory response syndrome (SIRS). We evaluated 57 critically ill patients, 34 with infectious SIRS (sepsis and septic shock), and 23 patients with noninfectious SIRS. Circulating Fas/Apo-1 was determined by a commercially available immunoassay. Our results clearly show that levels of Fas/Apo-1 were significantly elevated in patients with infectious and noninfectious SIRS (10.4 +/- 8.1 pg/mL, controls: 5.0 +/- 0.7 pg/mL; p < 0.0001). In addition, Fas/Apo-1 levels were not able in predicting in predicting poor outcome of patients with SIRS. In conclusion, these results show that increased levels of Fas/Apo-1 from patients with SIRS is a mechanism which contribute to inflammatory response through accumulation of neutrophils at sites of inflammation/infection.

An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma.

PubMed

Dima, Simona O; Tanase, Cristiana; Albulescu, Radu; Herlea, Vlad; Chivu-Economescu, Mihaela; Purnichescu-Purtan, Raluca; Dumitrascu, Traian; Duda, Dan G; Popescu, Irinel

2012-10-01

We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor α (TNF-α) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-α, IL-1β, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1β, and TNF-α correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-α correlated with CEA levels. Circulating IL-8, TNF-α, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.

Serum progranulin levels in relation to insulin resistance in childhood obesity.

PubMed

Alissa, Eman M; Sutaih, Rima H; Kamfar, Hayat Z; Alagha, Abdulmoeen E; Marzouki, Zuhair M

2017-11-27

Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases. A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Children were classified into four groups based on quartile for serum progranulin. Anthropometric variables were measured in all study subjects. Fasting blood samples were collected for measurement of blood glucose, insulin and lipid profile. Children within the upper quartile for serum progranulin concentration were heavier, more insulin resistant and had higher concentrations of serum total cholesterol, triglycerides, insulin and high sensitivity C reactive protein compared to those in the lower quartile. On correlation analysis, serum progranulin concentrations were significantly related to general and central adiposity, metabolic parameters, markers of inflammation and insulin resistance. Stepwise multiple regression showed that 26.6% of the variability in serum progranulin could be explained by measures of adiposity. The increased serum progranulin concentrations were closely related to measures of adiposity, metabolic parameters, inflammatory marker and insulin resistance indices, suggesting that progranulin may be an excellent biomarker for obesity in childhood.

Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.

PubMed

Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K

2013-07-09

The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

PubMed Central

Gertz, ER; Silverman, NE; Wise, KS; Hanson, KB; Alekel, DL; Stewart, JW; Perry, CD; Bhupathiraju, SN; Kohut, ML; Van Loan, MD

2010-01-01

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content and density (BMC, BMD) and determined the contribution of inflammatory markers to 1-year changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss (SIRBL) project who were randomly assigned to one of three treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy x-ray absorptiometry (DXA) and the 4% distal tibia (DT) by peripheral quantitative computed tomography (pQCT). Serum inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and white blood cell count (WBC)) were measured at baseline, 6 and 12 months. Due to attrition or missing values, data analysis at 12 months includes only 235 women. Significant associations among Il-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1% to 6.1% of the variance to the observed 12 month changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss. PMID:20605499

NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis

PubMed Central

Khandpur, Ritika; Carmona-Rivera, Carmelo; Vivekanandan-Giri, Anuradha; Gizinski, Alison; Yalavarthi, Srilakshmi; Knight, Jason S.; Friday, Sean; Li, Sam; Patel, Rajiv M.; Subramanian, Venkataraman; Thompson, Paul; Chen, Pojen; Fox, David A.; Pennathur, Subramaniam; Kaplan, Mariana J.

2013-01-01

The early events leading to the development of rheumatoid arthritis (RA) remain unclear but formation of autoantibodies to citrullinated antigens (ACPA) is considered a key pathogenic phenomenon. Neutrophils isolated from patients with various autoimmune diseases display enhanced extracellular trap formation (NETs), a phenomenon that externalizes autoantigens and immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and synovial fluid RA neutrophils, compared to neutrophils from healthy controls and from patients with osteoarthritis. Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. During NETosis, neutrophils externalized citrullinated autoantigens implicated in RA pathogenesis, whereas anti-citrullinated vimentin antibodies potently induced NET formation. The inflammatory cytokines IL-17A and TNF-α induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease. PMID:23536012

A population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence☆

PubMed Central

Khandaker, Golam M.; Zammit, Stanley; Lewis, Glyn; Jones, Peter B.

2014-01-01

Objective Schizophrenia is associated with atopy and increased inflammatory markers. We report a population-based longitudinal study of the associations between childhood atopic disorders, subsequent serum inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP), and the risk of psychotic experiences (PEs). Method PEs were assessed at age 13 years (n = 6785). Presence of clinician-diagnosed atopic disorders (asthma and eczema) was determined from parent-completed questionnaires at age 10 years (n = 7814). Serum IL-6 and CRP were measured at age 9 years (n = 5076). Logistic regression examined the association between (1) atopy and PEs, (2) inflammatory markers and PEs, and (3) mediating effects of inflammatory markers on the atopy–PEs association. Linear regression examined the association between atopy and inflammatory markers. Age, gender, social class, ethnicity and body mass index were included as potential confounders. Results At age 10 years, about 14% of the sample was reported to have asthma, 12% eczema, and 7% both asthma and eczema. Compared with children with no atopy, risk of PEs at age 13 years was increased for all of these groups; adjusted odds ratios (95% CI) were, respectively, 1.39 (1.10–1.77), 1.33 (1.04–1.69), and 1.44 (1.06–1.94). Atopy was associated with increased serum IL-6 and CRP; however, this did not mediate association between atopy and PEs. Inflammatory markers were not associated with later PEs. Conclusion Childhood atopic disorders increase the risk of psychotic experiences in adolescence. Follow-up of these individuals will be useful to determine the effect of atopy and inflammation on different trajectories of early-life PEs. PMID:24268471

A population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence.

PubMed

Khandaker, Golam M; Zammit, Stanley; Lewis, Glyn; Jones, Peter B

2014-01-01

Schizophrenia is associated with atopy and increased inflammatory markers. We report a population-based longitudinal study of the associations between childhood atopic disorders, subsequent serum inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP), and the risk of psychotic experiences (PEs). PEs were assessed at age 13 years (n=6785). Presence of clinician-diagnosed atopic disorders (asthma and eczema) was determined from parent-completed questionnaires at age 10 years (n=7814). Serum IL-6 and CRP were measured at age 9 years (n=5076). Logistic regression examined the association between (1) atopy and PEs, (2) inflammatory markers and PEs, and (3) mediating effects of inflammatory markers on the atopy-PEs association. Linear regression examined the association between atopy and inflammatory markers. Age, gender, social class, ethnicity and body mass index were included as potential confounders. At age 10 years, about 14% of the sample was reported to have asthma, 12% eczema, and 7% both asthma and eczema. Compared with children with no atopy, risk of PEs at age 13 years was increased for all of these groups; adjusted odds ratios (95% CI) were, respectively, 1.39 (1.10-1.77), 1.33 (1.04-1.69), and 1.44 (1.06-1.94). Atopy was associated with increased serum IL-6 and CRP; however, this did not mediate association between atopy and PEs. Inflammatory markers were not associated with later PEs. Childhood atopic disorders increase the risk of psychotic experiences in adolescence. Follow-up of these individuals will be useful to determine the effect of atopy and inflammation on different trajectories of early-life PEs. © 2013. Published by Elsevier B.V. All rights reserved.

Evidence for Anti-Inflammatory Effects of Exercise in CKD

PubMed Central

Kosmadakis, George C.; Watson, Emma L.; Bevington, Alan; Feehally, John; Bishop, Nicolette C.; Smith, Alice C.

2014-01-01

CKD is associated with a complex state of immune dysfunction characterized by immune depression, predisposing patients to infections, and immune activation, resulting in inflammation that associates with higher risk of cardiovascular disease. Physical exercise may enhance immune function and exert anti-inflammatory effects, but such effects are unclear in CKD. We investigated the separate effects of acute and regular moderate-intensity aerobic exercise on neutrophil degranulation (elastase release), activation of T lymphocytes (CD69 expression) and monocytes (CD86 and HLA-DR expression), and plasma inflammatory markers (IL-6, IL-10, soluble TNF-receptors, and C-reactive protein) in patients with predialysis CKD. A single 30-minute (acute) bout of walking induced a normal pattern of leukocyte mobilization and had no effect on T-lymphocyte and monocyte activation but improved neutrophil responsiveness to a bacterial challenge in the postexercise period. Furthermore, acute exercise induced a systemic anti-inflammatory environment, evidenced by a marked increase in plasma IL-10 levels (peaked at 1 hour postexercise), that was most likely mediated by increased plasma IL-6 levels (peaked immediately postexercise). Six months of regular walking exercise (30 min/d for 5 times/wk) exerted anti-inflammatory effects (reduction in the ratio of plasma IL-6 to IL-10 levels) and a downregulation of T-lymphocyte and monocyte activation, but it had no effect on circulating immune cell numbers or neutrophil degranulation responses. Renal function, proteinuria, and BP were also unaffected. These findings provide compelling evidence that walking exercise is safe with regard to immune and inflammatory responses and has the potential to be an effective anti-inflammatory therapy in predialysis CKD. PMID:24700875

Acute high-intensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes.

PubMed

Durrer, Cody; Francois, Monique; Neudorf, Helena; Little, Jonathan P

2017-04-01

Type 2 diabetes (T2D) is characterized by chronic low-grade inflammation that contributes to disease pathophysiology. Exercise has anti-inflammatory effects, but the impact of high-intensity interval training (HIIT) is not known. The purpose of this study was to determine the impact of a single session of HIIT on cellular, molecular, and circulating markers of inflammation in individuals with T2D. Participants with T2D ( n = 10) and healthy age-matched controls (HC; n = 9) completed an acute bout of HIIT (7 × 1 min at ~85% maximal aerobic power output, separated by 1 min of recovery) on a cycle ergometer with blood samples obtained before (Pre), immediately after (Post), and at 1 h of recovery (1-h Post). Inflammatory markers on leukocytes were measured by flow cytometry, and TNF-α was assessed in both LPS-stimulated whole blood cultures and plasma. A single session of HIIT had an overall anti-inflammatory effect, as evidenced by 1 ) significantly lower levels of Toll-like receptor (TLR) 2 surface protein expression on both classical and CD16+ monocytes assessed at Post and 1-h Post compared with Pre ( P < 0.05 for all); 2 ) significantly lower LPS-stimulated TNF-α release in whole blood cultures at 1-h Post ( P < 0.05 vs. Pre); and 3 ) significantly lower levels of plasma TNF-α at 1-h Post ( P < 0.05 vs. Pre). There were no differences between T2D and HC, except for a larger decrease in plasma TNF-α in HC vs. T2D (group × time interaction, P < 0.05). One session of low-volume HIIT has immunomodulatory effects and provides potential anti-inflammatory benefits to people with, and without, T2D. Copyright © 2017 the American Physiological Society.

Marrow Adipose Tissue in Older Men: Association with Visceral and Subcutaneous Fat, Bone Volume, Metabolism, and Inflammation.

PubMed

Bani Hassan, Ebrahim; Demontiero, Oddom; Vogrin, Sara; Ng, Alvin; Duque, Gustavo

2018-03-26

Marrow (MAT) and subcutaneous (SAT) adipose tissues display different metabolic profiles and varying associations with aging, bone density, and fracture risk. Using a non-invasive imaging methodology, we aimed to investigate the associations between MAT, SAT, and visceral fat (VAT) with bone volume, bone remodeling markers, insulin resistance, and circulating inflammatory mediators in a population of older men. In this cross-sectional study, 96 healthy men (mean age 67 ± 5.5) were assessed for anthropometric parameters, body composition, serum biochemistry, and inflammatory panel. Using single-energy computed tomography images, MAT (in L2 and L3 and both hips), VAT, and SAT (at the level of L2-L3 and L4-L5) were measured employing Slice-O-Matic software (Tomovision), which enables specific tissue demarcation applying previously reported Hounsfield unit thresholds. MAT volume was similar in all anatomical sites and independent of BMI. In all femoral regions of interest (ROIs) there was a strong negative association between bone and MAT volumes (r = - 0.840 to - 0.972, p < 0.001), with location-dependent variations in the lumbar spine. Unlike VAT and SAT, no associations between MAT and serum glucose, inflammatory markers or insulin resistance indicators were found. Bone decline occurred without red marrow expansion; thus lost bone was mainly (if not exclusively) replaced by MAT. In conclusion, strong inverse correlations between MAT and bone mass, which have been previously observed in women, were also confirmed in older men. However, MAT volume in all ROIs was interrelated and unlike women, mainly independent of VAT or SAT. The lack of strong association between MAT vs VAT/SAT, and its discordant associations with metabolic and inflammatory mediators provide further evidence on MAT's distinct attributes in older men.

The short-term effects of non-surgical periodontal therapy on the circulating levels of interleukin-6 and C-reactive protein in patients with chronic periodontitis

PubMed Central

George, Annie Kitty; Janam, Prasanthila

2013-01-01

Background: Recent epidemiological studies have shown that periodontal infection is a risk factor for a number of systemic diseases and conditions. In addition to the conventional risk factors, chronic infection and the subsequent generation of a systemic inflammatory response may be associated with this increased risk. Aims: This study was conducted to determine whether the presence of chronic periodontitis and subsequent non-surgical periodontal therapy could influence the serum levels of interleukin-6 and C-reactive protein (CRP) in patients with severe chronic generalized periodontitis. Settings and Design: Participants were selected from subjects who attended the Department of Periodontics and Oral Implantololgy, Government Dental College, Thiruvananthapuram. Materials and Methods: Sera were obtained from 25 patients with periodontitis for baseline examination and reassessment after completion of treatment. As a control, sera were also obtained from 20 subjects without periodontitis. Interleukin-6 was determined by sensitive enzyme-linked immunosorbent assay, and high-sensitivity CRP (hsCRP) was measured using latex turbidometric immunoassay. Statistical Analysis: Data were analyzed using computer software, Statistical Package for Social Sciences (SPSS) version 10. Results: The level of interleukin-6 and hsCRP in the sera of periodontitis patients was seen to be higher than those of healthy controls. Interleukin-6 level tended to decrease with improvement of the periodontal condition following treatment and approached that of control subjects, and this decline was statistically significant. The hsCRP levels also showed a decreasing trend following periodontal treatment. Conclusions: In this study, we were able to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers and that non-surgical periodontal therapy could bring about a decrease in the levels of these inflammatory markers. PMID:23633770

Effects of caffeine on the inflammatory response induced by a 15-km run competition.

PubMed

Tauler, Pedro; Martínez, Sonia; Moreno, Carlos; Monjo, Marta; Martínez, Pau; Aguiló, Antoni

2013-07-01

The objective of this study is as follows: 1) to determine the effects of caffeine supplementation on the inflammatory response (IL-6 and IL-10 levels and leukocyte numbers) induced by a 15-km run competition and 2) to examine the effect of caffeine supplementation on the energetic metabolites as well as on the exercise-induced oxidative stress. A double-blinded study of supplementation with caffeine was performed. Athletes participating in the study (n = 33) completed a 15-km run competition. Before competition, athletes took 6 mg · kg(-1) body weight of caffeine (caffeine group, n = 17) or a placebo (placebo group, n = 16). Blood samples were taken before and after competition (immediately and after 2-h recovery). Leukocyte numbers were determined in blood. Concentrations of oxidative stress markers, antioxidants, interleukins (IL-6 and IL-10), caffeine, adrenaline, and energetic metabolites were measured in plasma or serum. Caffeine supplementation induced higher increases in circulating total leukocytes and neutrophils, with significant differences between groups after recovery. Adrenaline, glucose, and lactate levels increased after exercise, with higher increases in the caffeine group. Exercise induced significant increases in IL-6 and IL-10 plasma levels, with higher increases in the caffeine group. Caffeine supplementation induced higher increases in oxidative stress markers after the competition. Caffeine supplementation induced higher levels of IL-6 and IL-10 in response to exercise, enhancing the anti-inflammatory response. The caffeine-induced increase in adrenaline could be responsible for the higher increase in IL-6 levels, as well as for the increased lactate levels. Furthermore, caffeine seems to enhance oxidative stress induced by exercise.

The short-term effects of non-surgical periodontal therapy on the circulating levels of interleukin-6 and C-reactive protein in patients with chronic periodontitis.

PubMed

George, Annie Kitty; Janam, Prasanthila

2013-01-01

Recent epidemiological studies have shown that periodontal infection is a risk factor for a number of systemic diseases and conditions. In addition to the conventional risk factors, chronic infection and the subsequent generation of a systemic inflammatory response may be associated with this increased risk. This study was conducted to determine whether the presence of chronic periodontitis and subsequent non-surgical periodontal therapy could influence the serum levels of interleukin-6 and C-reactive protein (CRP) in patients with severe chronic generalized periodontitis. Participants were selected from subjects who attended the Department of Periodontics and Oral Implantololgy, Government Dental College, Thiruvananthapuram. Sera were obtained from 25 patients with periodontitis for baseline examination and reassessment after completion of treatment. As a control, sera were also obtained from 20 subjects without periodontitis. Interleukin-6 was determined by sensitive enzyme-linked immunosorbent assay, and high-sensitivity CRP (hsCRP) was measured using latex turbidometric immunoassay. Data were analyzed using computer software, Statistical Package for Social Sciences (SPSS) version 10. The level of interleukin-6 and hsCRP in the sera of periodontitis patients was seen to be higher than those of healthy controls. Interleukin-6 level tended to decrease with improvement of the periodontal condition following treatment and approached that of control subjects, and this decline was statistically significant. The hsCRP levels also showed a decreasing trend following periodontal treatment. In this study, we were able to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers and that non-surgical periodontal therapy could bring about a decrease in the levels of these inflammatory markers.

Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a pilot study.

PubMed

Matejčíková, Z; Mareš, J; Přikrylová Vranová, H; Klosová, J; Sládková, V; Doláková, J; Zapletalová, J; Kaňovský, P

2015-02-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Autoimmune inflammation is common in the early stages of MS. This stage is followed by the neurodegenerative process. The result of these changes is axon and myelin breakdown. Although MS is according to McDonald's revised diagnostic criteria primarily a clinical diagnosis, paraclinical investigation methods are an important part in the diagnosis of MS. In common practice, magnetic resonance imaging of the brain and spinal cord, examination of cerebrospinal fluid (CSF) and examination of visual evoked potentials are used. There are an increasing number of studies dealing with biomarkers in CSF and their role in the diagnosis and treatment of MS. We hypothesized that the levels of some markers could be changed in MS in comparison with controls. We studied five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10 (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of beta-2-microglobulin and interleukin-8 in CSF were found to be significantly higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels of all markers between both groups were found. The levels of two studied inflammatory markers were found to be increased at the time of first clinical symptoms of MS. Research on the role of inflammatory and neurodegenerative markers in MS should continue.

Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.

PubMed

Alexander, Matthew R; Murgai, Meera; Moehle, Christopher W; Owens, Gary K

2012-04-02

Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1β represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1β modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1β- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1β distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1β exhibited over-representation of NF-κB binding sites, and NF-κB inhibition in SMCs reduced IL-1β-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-κB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1β-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD-induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1β- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-κB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo.

Inflammatory Markers and Preeclampsia: A Systematic Review.

PubMed

Black, Kathleen Darrah; Horowitz, June Andrews

Preeclampsia (PE), a serious and variable pregnancy complication affecting 5%-10% of the obstetric population, has an undetermined etiology, yet inflammation is concomitant with its development, particularly in relation to endothelial dysfunction. The purpose of this systematic review was to examine the published evidence concerning an association between PE and inflammatory markers for their usefulness in the prediction or early identification of women with PE in antepartum clinical settings. In this systematic review, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cumulative Index for Nursing and Allied Health and MEDLINE/OVID were the electronic databases used for identifying published articles. We placed no time limit on the publication year. The search generated 798 articles. After removing duplicates, screening abstracts, and conducting full-text reviews, we retained 73 articles and examined 57 unique markers. This review shows that C-reactive protein and the cytokines, specifically the proinflammatory markers IL-6, IL-8, and tumor necrosis factor alpha, garner the most support as potential inflammatory markers for clinical surveillance of PE, particularly during the second and third trimesters. Based on this review, we cannot recommend any single inflammatory marker for routine clinical use to predict/identify PE onset or progression. Research is recommended to examine a combination panel of these four inflammatory markers both with and without clinical risk factors toward the goal of translation to practice.

EFFECT OF INHALED ENDOTOXIN ON AIRWAY AND CIRCULATING INFLAMMATORY CELL PHAGOCYTOSIS AND CD11B EXPRESSION IN ATOPIC ASTHMATIC SUBJECTS

EPA Science Inventory

Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects

Neil E. Alexis, PhD, Marlowe W. Eldridge, MD, David B. Peden, MD, MS

Chapel Hill and Research Triangle Park, NC

Backgrou...

Financial strain, inflammatory factors, and haemoglobin A1c levels in African American women.

PubMed

Cutrona, Carolyn E; Abraham, William T; Russell, Daniel W; Beach, Steven R H; Gibbons, Frederick X; Gerrard, Meg; Monick, Martha; Philibert, Robert

2015-09-01

Type 2 diabetes disproportionately affects African American women, a population exposed to high levels of stress, including financial strain (Centers for Disease Control & Prevention, 2011, http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf). We tested a mediational model in which chronic financial strain among African American women contributes to elevated serum inflammation markers, which, in turn, lead to increased haemoglobin A1C (HbA1c) levels and risk for type 2 diabetes. We assessed level of financial strain four times over a 10-year period and tested its effect on two serum inflammation markers, C-reactive protein (CRP) and soluble interleukin-6 receptor (sIL-6R) in year 11 of the study. We tested the inflammation markers as mediators in the association between chronic financial strain and HbA1c, an index of average blood glucose level over several months. Data were from 312 non-diabetic African American women from the Family and Community Health Study (FACHS; Cutrona et al., 2000, J. Pers. Soc. Psychol., 79, 1088). Chronic financial strain predicted circulating sIL-6R after controlling for age, BMI, health behaviours, and physical health measures. In turn, sIL-6R significantly predicted HbA1c levels. The path between chronic financial strain and HbA1c was significantly mediated by sIL-6R. Contrary to prediction, CRP was not predicted by chronic financial strain. Results support the role of inflammatory factors in mediating the effects of psychosocial stressors on risk for type 2 diabetes. Findings have implications for interventions that boost economic security and foster effective coping as well as medical interventions that reduce serum inflammation to prevent the onset of type 2 diabetes. © 2014 The British Psychological Society.

Anti-inflammatory effect of water extracts of Graptopetalum paraguayense supplementation in subjects with metabolic syndrome: a preliminary study.

PubMed

Chen, Shu-Ju; Yen, Chi-Hua; Liu, Jen-Tzu; Tseng, Yu-Fen; Lin, Ping-Ting

2016-03-30

Many studies have demonstrated that Graptopetalum paraguayense has good antioxidant ability; however, few studies have examined its anti-inflammatory effect. The study aimed to investigate the anti-inflammatory effects of water extracts of G. paraguayense (WGP, 4 g day(-1)) in subjects with metabolic syndrome (MS). Intervention was administered for 12 weeks. Levels of inflammatory markers [high sensitivity C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6)] and antioxidant enzymes activities were measured. Forty-two subjects completed the 12 week intervention study (placebo, n = 19; WGP, n = 23). After 12 weeks supplementation, subjects in WGP group had significantly lower levels of inflammatory markers than the baseline (P < 0.05) and the placebo group (CRP, P = 0.07; TNF-α, P = 0.04; IL-6, P = 0.03). The changes in levels of the inflammatory markers were significantly decreased in WGP group (CRP, P = 0.04; TNF-α, P = 0.06; IL-6, P = 0.01) compared to the placebo group. Levels of inflammatory markers were significantly negatively correlated with the antioxidant enzymes activities after supplementation. This study demonstrated a significant reduction in inflammatory status in MS after WGP supplementation. WGP may exert an anti-inflammatory effect on MS in addition to its antioxidant ability. © 2015 Society of Chemical Industry.

Gender, Race/Ethnicity, Personality, and Interleukin-6 in Urban Primary Care Patients

PubMed Central

Chapman, Benjamin P.; Khan, Ayesha; Harper, Mary; Stockman, Doug; Fiscella, Kevin; Walton, James; Duberstein, Paul; Talbot, Nancy; Lyness, Jeffrey M.; Moynihan, Jan

2009-01-01

Gender, race/ethnicity, and personality are markers of significant psychosocial and biological variability. Each may have implications for allostatic load and resulting inflammatory processes, yet findings have been largely mixed. We investigated whether women, minorities, and those higher in Neuroticism and lower in Extraversion were at risk for elevated circulating levels of the pro-inflammatory cytokine interleukin (IL)-6 in a sample of 103 middle aged and older urban primary care patients. Regression analyses controlling for age, education, current depression levels, and chronic medical conditions revealed that women, minorities, and individuals lower in Extraversion had higher circulating levels of IL-6. Analyses of more specific personality traits revealed that the sociability and positive emotions components of Extraversion were unassociated with IL-6, but the activity facet--reflecting dispositional vigor and energy--was robustly associated with IL-6. The difference between high (+1 Standard Deviation (SD)) and low (−1 SD) trait activity was sufficient to shift IL-6 levels beyond a previously established high risk cut-point in both white and minority women. These findings suggest that while broad group differences between genders and races/ethnicities exist, personality represents an important source of individual differences in inflammation within groups. Future work should examine to what extent IL-6 levels are linked to temperament or genetic activity levels vs. physical activity itself, and whether IL-6 levels may be reduced by boosting regular activity levels in demographic segments such as women and minorities who appear susceptible to greater inflammation. PMID:19162168

Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat, Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study

PubMed Central

Van Loan, Marta D.; Keim, Nancy L.; Adams, Sean H.; Souza, Elaine; Woodhouse, Leslie R.; Thomas, Anthony; Witbracht, Megan; Gertz, Erik R.; Piccolo, Brian; Bremer, Andrew A.; Spurlock, Michael

2011-01-01

Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD) or ≤4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT), subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered. PMID:21941636

Gene expression profiling and functional characterization of macrophages in response to circulatory microparticles produced during Trypanosoma cruzi infection and Chagas disease

PubMed Central

Chowdhury, Imran; Koo, Sue-jie; Gupta, Shivali; Liang, Lisa Yi; Bahar, Bojlul; Silla, Laura; Burgos, Julio Nuñez; Barrientos, Natalia; Zago, Maria Paola; Garg, Nisha Jain

2016-01-01

BACKGROUND Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host’s signature of inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHDOS The MPs were harvested from supernatants of human PBMCs in vitro incubated with T. cruzi (control: LPS-treated), plasma of seropositive humans with clinically asymptomatic (CA) or symptomatic (CS) disease state (normal/healthy (NH) controls) and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of macrophage activation by flow cytometry, cytokine profile by an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by colorimetric and fluorometric assays. RESULTS Tc- and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile and •NO release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc-MPs. Endothelial cells, T lymphocytes and mφs were the major source of MPs shed in plasma of chagasic humans and experimentally infected mice. The CS-MPs and CA-MPs (vs. NH-MPs) elicited >2-fold increase in •NO and mitochondrial oxidative stress in THP-1 mφs; however, CS-MPs (vs. CA-MPs) elicited a more pronounced and disease-state-specific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2 and CCL3), cytokine release (IL2+IFNγ>GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of non-vaccinated/infected mice induced 7.5-fold and 40% increase in •NO and IFNγ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. CONCLUSION Circulating MPs reflect in vivo levels of oxidative, nitrosative, and inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies against CCM. PMID:27902980

Chronic inflammation and risk of colorectal and other obesity-related cancers: The health, aging and body composition study.

PubMed

Izano, Monika; Wei, Esther K; Tai, Caroline; Swede, Helen; Gregorich, Steven; Harris, Tamara B; Klepin, Heidi; Satterfield, Suzanne; Murphy, Rachel; Newman, Anne B; Rubin, Susan M; Braithwaite, Dejana

2016-03-01

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults. © 2015 UICC.

Intranasal post-cardiac arrest treatment with orexin-A facilitates arousal from coma and ameliorates neuroinflammation.

PubMed

Modi, Hiren R; Wang, Qihong; Gd, Sahithi; Sherman, David; Greenwald, Elliot; Savonenko, Alena V; Geocadin, Romergryko G; Thakor, Nitish V

2017-01-01

Cardiac arrest (CA) entails significant risks of coma resulting in poor neurological and behavioral outcomes after resuscitation. Significant subsequent morbidity and mortality in post-CA patients are largely due to the cerebral and cardiac dysfunction that accompanies prolonged whole-body ischemia post-CA syndrome (PCAS). PCAS results in strong inflammatory responses including neuroinflammation response leading to poor outcome. Currently, there are no proven neuroprotective therapies to improve post-CA outcomes apart from therapeutic hypothermia. Furthermore, there are no acceptable approaches to promote cortical or cognitive arousal following successful return of spontaneous circulation (ROSC). Hypothalamic orexinergic pathway is responsible for arousal and it is negatively affected by neuroinflammation. However, whether activation of the orexinergic pathway can curtail neuroinflammation is unknown. We hypothesize that targeting the orexinergic pathway via intranasal orexin-A (ORXA) treatment will enhance arousal from coma and decrease the production of proinflammatory cytokines resulting in improved functional outcome after resuscitation. We used a highly validated CA rat model to determine the effects of intranasal ORXA treatment 30-minute post resuscitation. At 4hrs post-CA, the mRNA levels of proinflammatory markers (IL1β, iNOS, TNF-α, GFAP, CD11b) and orexin receptors (ORX1R and ORX2R) were examined in different brain regions. CA dramatically increased proinflammatory markers in all brain regions particularly in the prefrontal cortex, hippocampus and hypothalamus. Post-CA intranasal ORXA treatment significantly ameliorated the CA-induced neuroinflammatory markers in the hypothalamus. ORXA administration increased production of orexin receptors (ORX1R and ORX2R) particularly in hypothalamus. In addition, ORXA also resulted in early arousal as measured by quantitative electroencephalogram (EEG) markers, and recovery of the associated behavioral neurologic deficit scale score (NDS). Our results indicate that intranasal delivery of ORXA post-CA has an anti-inflammatory effect and accelerates cortical EEG and behavioral recovery. Beneficial outcomes from intranasal ORXA treatment lay the groundwork for therapeutic clinical approach to treating post-CA coma.

Association of constitutional type of Ayurveda with cardiovascular risk factors, inflammatory markers and insulin resistance

PubMed Central

Mahalle, Namita P.; Kulkarni, Mohan V.; Pendse, Narendra M.; Naik, Sadanand S.

2012-01-01

Context: Ayurveda propounds that diseases manifest from imbalance of doshas. There, have been attempts to indicate biochemical basis of constitutional types described in Ayurveda. Aims: The study was intended to assess the association of constitutional types (Prakriti) with cardiovascular risk factors, inflammatory markers and insulin resistance in subjects with coronary artery disease (CAD). Settings and Design: Hospital based cross sectional study. Materials and Methods: Three hundred patients with CAD >25 years were studied. Assessment of Prakriti was done by using Ayusoft software. Biochemical parameters, inflammatory markers (hsCRP, TNF-alpha and IL-6) and insulin resistance (HOMA-IR) were measured. Statistical Analysis: Was done using EPI INFO, version 3.5.3. Results: Mean age of patients was 60.97±12.5 years. Triglyceride, VLDL and LDL was significantly higher (P<0.0001, P<0.0001 and 0.0355, respectively) and HDL cholesterol (P<0.0001) significantly lower in vatta kapha (VK) Prakriti when compared with other constitution type. VK Prakriti was correlated with diabetes mellitus (r=0.169, P=0.003), hypertension (r=0.211, P≤0.0001) and dyslipidemia (r=0.541, P≤0.0001). Inflammatory markers; IL6, TNF alpha, hsCRP and HOMA IR was highest in VK Prakriti. Inflammatory markers were correlated positively with both VK and Kapha group. Conclusions: There is strong relation of risk factors (diabetes, hypertension, dyslipidemia), insulin resistance, and inflammatory markers with Vata Kapha and Kapha Prakriti. PMID:23125512

Significance of the DNA-Histone Complex Level as a Predictor of Major Adverse Cardiovascular Events in Hemodialysis Patients: The Effect of Uremic Toxin on DNA-Histone Complex Formation.

PubMed

Jeong, Jong Cheol; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Ryu, Ji Won; Kim, Dong Ki; Joo, Kwon Wook; Kim, Hyun Kyung

2016-01-01

Neutrophils can release the DNA-histone complex into circulation following exposure to inflammatory stimuli. This prospective study investigated whether the DNA-histone complex and other biomarkers could predict major cardiovascular adverse events (MACEs) in hemodialysis (HD) patients. The levels of circulating DNA-histone complexes, cell-free DNA, interleukin (IL)-6, and neutrophil elastase were measured in 60 HD patients and 28 healthy controls. MACE was assessed at 24 months. Uremic toxin-induced neutrophil released contents were measured in vitro. Compared with controls, HD patients showed higher levels of DNA-histone complexes and IL-6. The DNA-histone complex level was inversely associated with the Kt/V. In a multivariable Cox analysis, the high level of DNA-histone complexes was a significant independent predictor of MACE. The uremic toxins induced DNA-histone complex formation in normal neutrophils in vitro. The DNA-histone complex is a potentially useful marker to predict MACE in HD patients. Uremic toxins induced DNA-histone complex formation in vitro. © 2015 S. Karger AG, Basel.

Inflammatory biomarkers in heart failure revisited: much more than innocent bystanders.

PubMed

von Haehling, Stephan; Schefold, Joerg C; Lainscak, Mitja; Doehner, Wolfram; Anker, Stefan D

2009-10-01

Chronic heart failure is viewed as a state of chronic inflammation. Many inflammatory markers have been shown to be up-regulated in patients who have this condition, but the markers' roles in clinical decision making have not yet been fully elucidated. A panel of biomarkers is likely to have a strong impact on patient management. Inflammatory biomarkers are interesting candidates that could answer specific clinical questions on their own or complement a multi-marker approach. This article provides a broad overview of several inflammatory biomarkers, including the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL-1, IL-18, and the soluble receptors TNFR-1, TNFR-2, IL-6R, and gp130. In addition to these acute phase reactants, several adhesion molecules, and lipopolysaccharide-signaling pathways are discussed.

Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice

PubMed Central

Subramanian, Savitha; Han, Chang Yeop; Chiba, Tsuyoshi; McMillen, Timothy S.; Wang, Shari A.; Haw, Antonio; Kirk, Elizabeth A.; O’Brien, Kevin D.; Chait, Alan

2009-01-01

Objective Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease. Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor-deficient (LDLR-/-) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis. Methods and Results LDLR-/- mice were fed chow, high fat, high carbohydrate (diabetogenic) diet without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation and local inflammation were observed in intra-abdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group. Conclusions Obesity-induced macrophage accumulation in adipose tissue is exacerbated by dietary cholesterol. These local inflammatory changes in adipose tissue are associated with insulin resistance, systemic inflammation and increased atherosclerosis in this mouse model. PMID:18239153

Inflammaging and human longevity in the omics era.

PubMed

Monti, Daniela; Ostan, Rita; Borelli, Vincenzo; Castellani, Gastone; Franceschi, Claudio

2017-07-01

Inflammaging is a recent theory of aging originally proposed in 2000 where data and conceptualizations regarding the aging of the immune system (immunosenescence) and the evolution of immune responses from invertebrates to mammals converged. This theory has received an increasing number of citations and experimental confirmations. Here we present an updated version of inflammaging focused on omics data - particularly on glycomics - collected on centenarians, semi-supercentenarians and their offspring. Accordingly, we arrived to the following conclusions: i) inflammaging has a structure where specific combinations of pro- and anti-inflammatory mediators are involved; ii) inflammaging is systemic and more complex than we previously thought, as many organs, tissues and cell types participate in producing pro- and anti-inflammatory stimuli defined "molecular garbage"; iii) inflammaging is dynamic, can be propagated locally to neighboring cells and systemically from organ to organ by circulating products and microvesicles, and amplified by chronic age-related diseases constituting a "local fire", which in turn produces additional inflammatory stimuli and molecular garbage; iv) an integrated Systems Medicine approach is urgently needed to let emerge a robust and highly informative set/combination of omics markers able to better grasp the complex molecular core of inflammaging in elderly and centenarians. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The potential predictive value of circulating immune cell ratio and tumor marker in atezolizumab treated advanced non-small cell lung cancer patients.

PubMed

Zhuo, Minglei; Chen, Hanxiao; Zhang, Tianzhuo; Yang, Xue; Zhong, Jia; Wang, Yuyan; An, Tongtong; Wu, Meina; Wang, Ziping; Huang, Jing; Zhao, Jun

2018-05-04

The PD-L1 antibody atezolizumab has shown promising efficacy in patients with advanced non-small cell lung cancer. But the predictive marker of clinical benefit has not been identified. This study aimed to search for potential predictive factors in circulating blood of patients receiving atezolizumab. Ten patients diagnosed with advanced non-small cell lung cancer were enrolled in this open-label observing study. Circulating immune cells and plasma tumor markers were examined in peripheral blood from these patients before and after atezolizumab treatment respectively. Relation between changes in circulating factors and anti-tumor efficacy were analyzed. Blood routine test showed that atezolizumab therapy induced slightly elevation of white blood cells count generally. The lymphocyte ratio was increased slightly in disease controlled patients but decreased prominently in disease progressed patients in response to atezolizumab therapy. Flow cytometric analysis revealed changes in percentage of various immune cell types, including CD4+ T cell, CD8+ T cell, myeloid-derived suppressor cell, regulatory T cell and PD-1 expressing T cell after atezolizumab. Levels of plasma tumor marker CEA, CA125 and CA199 were also altered after anti-PD-L1 therapy. In comparison with baseline, the disease progressed patients showed sharp increase in tumor marker levels, while those disease controlled patients were seen with decreased regulatory T cell and myeloid-derived suppressor cell ratios. The circulating immune cell ratios and plasma tumor marker levels were related with clinical efficacy of atezolizumab therapy. These factors could be potential predictive marker for anti-PD-L1 therapy in advanced non-small cell lung cancer.

Increase of endothelial progenitor cells in acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

PubMed

Medinger, Michael; Heim, Dominik; Gerull, Sabine; Halter, Jörg; Krenger, Werner; Buser, Andreas; Lengerke, Claudia; Bucher, Christoph; Passweg, Jakob

2016-08-01

Circulating endothelial progenitor cells (EPCs; CD31+ CD34(bright)CD133+ CD45(dim) cells) are novel markers of endothelial dysfunction and related to inflammatory processes such as acute graft-versus-host disease (aGvHD). 47 patients with acute myeloid leukaemia (AML) who were in complete remission as they underwent allogeneic hematopoietic stem cell transplantation with myeloablative conditioning with PBSC as stem cell source were enrolled in the study. Blood samples for the quantitative analysis of circulating EPC levels were drawn at different time points in patients with and without aGvHD. CD34+ VEGFR2/KDR+ CD133+ triple-positive cells identified among CD34+ cells by FACS. EPC were quantified and data are presented as cells/ml whole blood. Circulating EPC levels were not significantly different in patients with and without aGvHD prior to conditioning (baseline) and at the time of engraftment. However, at diagnosis of aGvHD≥grade 2, EPC levels increased whereas in patients without aGvHD the EPC levels remained significantly lower (3021±278 versus 2322±195 cells/ml; p<0.001). Patients with steroid-refractory aGvHD had high levels of EPC throughout. EPC levels fell in responding patients. Our results demonstrate that the number of circulating EPCs is increased in patients with aGvHD compared to patients without aGvHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

DTIC Science & Technology

fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

Atorvastatin May Correct Dyslipidemia in Adult Patients at Risk for Alzheimer's Disease Through an Anti-Inflammatory Pathway.

PubMed

Zhao, Liandong; Zhao, Qitao; Zhou, Yong; Zhao, Ying; Wan, Qi

2016-01-01

Dyslipidemia is a risk factor for the pathogenesis of Alzheimer's disease. Although, atorvastatin is a well-accepted lipid-lowering agent, the benefits of atorvastatin treatment through an anti-inflammatory mechanism are still unclear. The present study was designed to examine changes in inflammatory markers following administration of atorvastatin in dyslipidemic patients with a parental history of Alzheimer's disease. Dyslipidemic adults with a parental history of Alzheimer's disease were administered either 40 mg of atorvastatin or placebo for 18 months. Before and after the study, lpid levels, blood pressure, body weight and body mass index, and the inflammatory markers hs-Creactive protein, serum monocyte chemoattractant protien-1, interleukin-1β, interleukin-6, and tumor necrosis factor-α were tested. Baseline levels of lipids, body mass index, hs-Creactive protein, monocyte chemoattractant protien-1, interleukin- 1β, interleukin-6 and tumor necrosis factor-α did not show any difference between the two groups. However, after 18 months of atorvastatin treatment, all inflammatory markers significantly decreased in association with a reduction of lipid profiles, body mass index, bodyweight, and blood pressure, compared with those patients treated with placebo. Administration of atorvastatin corrected dyslipidemia in association with a reduction in inflammatory markers. Our results suggest that the therapeutic benefits of atorvastatin possibly involve an anti-inflammatory pathway.

SOURCE APPORTIONMENT OF FINE PARTICLES IN THE U.S. AND ASSOCIATIONS BETWEEN INFLAMMATORY MARKER IL -8

EPA Science Inventory

Associations are well established between particulate matter (PM) and increased human mortality and morbidity. The association between PM sources and inflammatory marker IL-8 was evaluated in this study.

INFLAMMATORY MARKERS ASSOCIATED WITH TRAUMA AND INFECTION IN RED-TAILED HAWKS (BUTEO JAMAICENSIS) IN THE USA.

PubMed

Lee, Kelly A; Goetting, Valerie S; Tell, Lisa A

2015-10-01

Changes in inflammatory marker concentrations or activity can be used to monitor health and disease condition of domestic animals but have not been applied with the same frequency to wildlife. We measured concentrations or activity of six inflammatory markers (ceruloplasmin, haptoglobin, mannan-binding lectin-dependent complement [MBL/complement], unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC), and plasma iron) in apparently healthy and sick or injured Red-tailed Hawks (Buteo jamaicensis). Haptoglobin and ceruloplasmin activities were consistently elevated in sick or injured hawks (2.1 and 2.5 times higher, respectively), and plasma iron concentrations decreased (0.46 times lower), relative to those of healthy birds. There were no differences between healthy and unhealthy hawks in TIBC and UIBC concentrations or MBL/complement activity. Therefore, haptoglobin, ceruloplasmin, and plasma iron would be useful inclusions in a panel of inflammatory markers for monitoring health in raptors.

Comparative usefulness of inflammatory markers to indicate bacterial infection-analyzed according to blood culture results and related clinical factors.

PubMed

Nishikawa, Hirokazu; Shirano, Michinori; Kasamatsu, Yu; Morimura, Ayumi; Iida, Ko; Kishi, Tomomi; Goto, Tetsushi; Okamoto, Saki; Ehara, Eiji

2016-01-01

To assess relationships of inflammatory markers and 2 related clinical factors with blood culture results, we retrospectively investigated inpatients' blood culture and blood chemistry findings that were recorded from January to December 2014 using electronic medical records and analyzed the data of 852 subjects (426 culture-positive and 426 culture-negative). Results suggested that the risk of positive blood culture statistically increased as inflammatory marker levels and the number of related factors increased. Concerning the effectiveness of inflammatory markers, when the outcome definition was also changed for C-reactive protein (CRP), the odds ratio had a similar value, whereas when the outcome definition of blood culture positivity was used for procalcitonin (PCT), the greatest effectiveness of that was detected. Therefore, the current results suggest that PCT is more useful than CRP as an auxiliary indication of bacterial infection. Copyright © 2016 Elsevier Inc. All rights reserved.

New biochemical markers: from bench to bedside.

PubMed

Zaninotto, Martina; Mion, Monica Maria; Novello, Enrica; Altinier, Sara; Plebani, Mario

2007-05-01

Evaluation of patients presenting to hospital with chest pain or other signs or symptoms suggesting acute coronary syndrome (ACS) is problematic, time-consuming and sometimes expensive, even if new biochemical markers, such as troponins, have improved the ability to detect cardiac injury. However, patients with normal troponin values are not necessarily risk-free for major cardiac events. Recent investigations indicate that the overall patient risk may be assessed earlier than before, thanks to new knowledge acquired concerning the pathobiology of atherosclerosis and molecular events involved in the progression of disease, thus allowing the development of new biochemical markers. Some selected markers are released during the different phases of development of cardiovascular disease and may be useful for the diagnosis of patients with cardiovascular disease. In particular, the identification of emerging markers that provide relevant information on the inflammatory process, and the development of biomarkers whose circulating concentrations suggest the status of plaque instability and rupture, seems to be of particular value in prognosis and risk stratification. The overall expectations for a cardiovascular biochemical marker are not only its biological plausibility but also the availability at a reasonable cost of rapid, high quality assays, and their correct interpretation by clinicians using optimal cut-offs. The crossing from bench to bedside for each new marker discovered, must be associated with concurrent advances in the characterization of analytical features and the development of routine assay, in the assessment of analytical performance and in interpretative reporting of test results as well as in the training of physicians to use the array of biomarkers available appropriately and to interpret them correctly. This approach calls for the coordinated support of clinicians, technology experts, statisticians and the industry so that new biochemical developments can be of optimal value.

Longitudinal Relationship of Low Leisure Satisfaction but not Depressive Symptoms With Systemic Low-Grade Inflammation in Dementia Caregivers

PubMed Central

2014-01-01

Objectives. This study aimed to further elucidate the biobehavioral mechanisms linking dementia caregiving with an increased cardiovascular disease risk. We hypothesized that both elevated depressive symptoms and a behavioral correlate of depression, low leisure satisfaction, are associated with systemic inflammation. Method. We studied 121 elderly Alzheimer’s disease caregivers who underwent 4 annual assessments for depressive symptoms, leisure satisfaction, and circulating levels of inflammatory markers. We used mixed-regression analyses controlling for sociodemographic and health-relevant covariates to examine longitudinal relationships between constructs of interest. Results. There were inverse relationships between total leisure satisfaction and tumor necrosis factor-α (TNF-α; p = .047), interleukin-8 (IL-8; p < .001), and interferon-γ (IFG; p = .020) but not with IL-6 (p = .21) and C-reactive protein (p = .65). Lower enjoyment from leisure activities was related to higher levels of TNF-α (p = .045), IL-8 (p < .001), and IFG (p = .002), whereas lower frequency of leisure activities was related only to higher IL-8 levels (p = .023). Depressive symptoms were not associated with any inflammatory marker (all p values > .17). Depressive symptoms did not mediate the relationship between leisure satisfaction and inflammation. Discussion. Lower satisfaction with leisure activities is related to higher low-grade systemic inflammation. This knowledge may provide a promising way of improving cardiovascular health in dementia caregivers through behavioral activation treatments targeting low leisure satisfaction. PMID:23650246

Effects of oral supplementation with omega-3 fatty acids on nutritional state and inflammatory markers in maintenance hemodialysis patients.

PubMed

Gharekhani, Afshin; Khatami, Mohammad-Reza; Dashti-Khavidaki, Simin; Razeghi, Effat; Abdollahi, Alireza; Hashemi-Nazari, Seyed-Saeed; Mansournia, Mohammad-Ali

2014-05-01

The objective was to determine the effects of omega-3 supplementation on nutritional state and inflammatory markers of hemodialysis patients. This was a randomized, placebo-controlled trial. Adult patients undergoing maintenance hemodialysis were included. Patients with malignancy, pregnancy, concurrent inflammatory or infectious diseases, or concomitant use of any medication affecting inflammation status were excluded. The omega-3 group received 6 soft-gel capsules of fish oil (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid in each) daily for 4 months, and the placebo group received corresponding paraffin oil capsules.Nutrition indices including body mass index; mid-arm muscle circumference; serum concentrations of albumin, prealbumin, and transferrin; and serum levels of inflammatory/anti-inflammatory markers including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, C-reactive protein, ferritin, parathyroid hormone, and ratios of IL-10 to TNF-α and IL-10 to IL-6 were measured before and after 4 months of intervention. Twenty patients in the placebo and 25 patients in the omega-3 group completed the study. There were no significant changes in nutritional markers between the omega-3 and placebo groups after 4 months of intervention. Regression analysis adjusting post-treatment values of nutrition markers for baseline values, omega-3 treatment, and patients' baseline demographic and clinical data revealed that omega-3 treatment was a significant independent predictor of increased serum prealbumin level (182.53; 95% confidence interval 21.14, 511.18; P = .11). Although slight reduction of inflammatory state was observed in the omega-3 group, no significant differences were evident in the mean changes of inflammatory and anti-inflammatory markers between the 2 groups with the exception of serum ferritin level and the IL-10 to IL-6 ratio, which significantly changed in favor of omega-3 supplementation (P < .001 and P = .003, respectively). Omega-3 supplementation in hemodialysis patients produced a slight attenuation in systemic inflammation without any remarkable effects on nutritional markers. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Serum Levels of Inflammatory Markers in Depressed Elderly Patients with Diabetes and Mild Cognitive Impairment

PubMed Central

Gorska-Ciebiada, Malgorzata; Saryusz-Wolska, Malgorzata; Borkowska, Anna; Ciebiada, Maciej; Loba, Jerzy

2015-01-01

Objective The aim of the study was to determine the serum levels of CRP, IL-6 and TNF-α in elderly diabetic patients with depressive syndrome alone or with coexisting mild cognitive impairment (MCI). Methods 276 diabetics elders were screened for depressive symptoms (using Geriatric Depression Scale: GDS-30) and MCI (using the Montreal Cognitive Assessment: MoCA score). Data of HbA1c, blood lipids and inflammatory markers levels were collected. Results In all groups of patients levels of CRP, IL-6 and TNF-α were significantly higher as compared to controls. The highest level of inflammatory markers was detected in group with depressive mood and coexisting MCI, however IL-6 level didn’t significantly differ as compared to MCI group. We founded correlations between all inflammatory markers in group of patients with depressive mood and in group of subjects with depressive symptoms and coexisting MCI. GDS-30 score was correlated with levels of inflammatory markers in group with depressive mood, and with levels of CRP and TNF-α in group with depressive mood and coexisting MCI. In the group with depressive mood and coexisting MCI we founded that MoCA score was negatively correlated with CRP and TNF-α levels; and HbA1c level was positively correlated with all inflammatory markers. The univariate logistic regression models revealed that variables which increased the likelihood of having been diagnosed with MCI in depressed patients were: higher levels of HbA1c, CRP, IL-6 and TNF-α, previous CVD or stroke, increased number of co-morbidities and microvascular complications, older age, less years of formal education. The multivariable model showed that previous CVD, higher HbA1c and IL-6 levels are significant factors. Conclusions We demonstrated that the presence of depressive syndrome is associated with higher levels of inflammatory markers in elderly patients with diabetes. The presence of MCI in these depressed subjects has additive effect on levels of inflammatory mediators. PMID:25793613

Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

PubMed Central

Swellam, Menha; Samy, Nervana; Abdl Wahab, Susan; Ibrahim, Mohamed Saeed

2009-01-01

Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations. Materials and methods: We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays. Results: Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P < 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnant vs PE or normotensive pregnant vs PE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity. Conclusions: Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE. PMID:19597295

Liver failure induces a systemic inflammatory response. Prevention by recombinant N-terminal bactericidal/permeability-increasing protein.

PubMed Central

Boermeester, M. A.; Houdijk, A. P.; Meyer, S.; Cuesta, M. A.; Appelmelk, B. J.; Wesdorp, R. I.; Hack, C. E.; Van Leeuwen, P. A.

1995-01-01

The observed increased susceptibility of patients with fulminant hepatic failure for local and systemic infections has been hypothesized to be due to a failure for the hepatic clearance function and subsequent leaking of endogenous endotoxins into the systemic circulation. However, experimental evidence for such a systemic inflammation during liver failure due to endogenous endotoxemia is lacking. Therefore, we designed a study to clarify whether circulating endotoxins due to liver failure could lead to the development of systemic inflammations. In a rat model for liver failure induced by a two-thirds partial hepatectomy, we evaluated the course of circulating tumor necrosis factor and interleukin-6, changes in blood chemistry and hemodynamics, and histopathological changes in the lungs. Partially hepatectomized animals, but not sham-operated animals, demonstrated cardiac failure, increased levels of creatinin and urea, metabolic acidosis, high plasma levels of tumor necrosis factor and interleukin-6, and an influx of PMNs in the lungs-together indicating the development of a systemic inflammatory response. Continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23), a well described endotoxin-neutralizing protein, prevented these inflammatory reactions. Ex vivo experiments with rat plasma samples confirmed the presence of circulating endotoxins in partially hepatectomized rats as opposed to those treated with rBPI23. Thus, our results indicate that the early phase of liver failure induces a systemic inflammatory response triggered by circulating endotoxins, which can be prevented by perioperative infusion of rBPI23. Images Figure 2 PMID:7485405

Erratum to: Circulating tumor markers: a guide to their appropriate clinical use | Comparative summary of recommendations from clinical practice guidelines (PART 1), (PART 2), (PART 3).

PubMed

2017-10-31

Erratum To: Circulating tumor markers: a guide to their appropriate clinical use | Comparative summary of recommendations from clinical practice guidelines (PART 1) Gion M, Trevisiol C, Rutjes AW, Rainato G, Fabricio AS. Int J Biol Markers. 2016 Dec 23;31(4):e332-e367. doi: 10.5301/jbm.5000251. Circulating tumor markers: a guide to their appropriate clinical use | Comparative summary of recommendations from clinical practice guidelines (PART 2).Gion M, Trevisiol C, Rutjes AWS, Rainato G, Fabricio ASC. Int J Biol Markers. 2017 Mar 2;32(1):e1-e52. doi: 10.5301/ijbm.5000259. Circulating tumor markers: a guide to their appropriate clinical use | Comparative summary of recommendations from clinical practice guidelines (PART 3).Gion M, Trevisiol C, Rutjes AWS, Rainato G, Fabricio ASC. Int J Biol Markers. 2017 May 4;32(2):e147-e181. doi: 10.5301/ijbm.5000272. We report an amendment in the Detailed summary tables pages of the three parts of the guidelines above. The correct definition of detailed summary tables is reported below. Definition and target audience Detailed summary tables are tables prepared for every tumor type which report recommendations and supplementary information from different guidance documents with enough details to be useful for health care providers, policy makers (for potential adaptation to specific settings) and staff developing educational material informed by available evidence.

Zingerone Suppresses Liver Inflammation Induced by Antibiotic Mediated Endotoxemia through Down Regulating Hepatic mRNA Expression of Inflammatory Markers in Pseudomonas aeruginosa Peritonitis Mouse Model

PubMed Central

Kumar, Lokender; Chhibber, Sanjay; Harjai, Kusum

2014-01-01

Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti-inflammatory phytomedicine against hepatic inflammation induced by antibiotic mediated endotoxemia. These results thus suggest that zingerone treatment can be used as a co-therapy with antibiotics to reduced endotoxin induced inflammation during treatment of severe P.aeruginosa infections. PMID:25184525

Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

PubMed

Kumar, Lokender; Chhibber, Sanjay; Harjai, Kusum

2014-01-01

Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti-inflammatory phytomedicine against hepatic inflammation induced by antibiotic mediated endotoxemia. These results thus suggest that zingerone treatment can be used as a co-therapy with antibiotics to reduced endotoxin induced inflammation during treatment of severe P.aeruginosa infections.

EMMPRIN and its ligand cyclophilin A as novel diagnostic markers in inflammatory cardiomyopathy.

PubMed

Seizer, Peter; Geisler, Tobias; Bigalke, Boris; Schneider, Martin; Klingel, Karin; Kandolf, Reinhard; Stellos, Konstantinos; Schreieck, Jürgen; Gawaz, Meinrad; May, Andreas E

2013-03-10

During inflammatory cardiomyopathy matrix metalloproteinases are crucially involved in cardiac remodeling. The aim of the present study was to investigate whether the "extracellular matrix metalloproteinase inducer" EMMPRIN (CD147) and its ligand Cyclophilin A (CyPA) are upregulated in inflammatory cardiomyopathy and may serve as diagnostic markers. Therefore, a series of 102 human endomyocardial biopsies were analyzed for the expression of EMMPRIN and CyPA and correlated with histological and immunohistological findings. Endomyocardial biopsies were stained for EMMPRIN and CyPA in addition to standard histology (HE, Trichrom) and immunohistological stainings (MHC-II, CD68, CD3). 39 (38.2%) biopsies met the immunohistological criteria of an inflammatory cardiomyopathy. EMMPRIN, which was predominantly expressed on cardiomyocytes, was slightly (but significantly) upregulated in non inflammatory cardiomyopathies compared to normal histopathological findings and highly upregulated in inflammatory cardiomyopathy compared to both non inflammatory cardiomyopathy and normal histopathology. In contrast, CyPA reveals no enhanced expression in non inflammatory cardiomyopathies and a highly enhanced expression in inflammatory cardiomyopathy, where it is closely associated with leucocytes infiltrates. We found a strong correlation between both EMMPRIN and CyPA with the expression of MHC-II molecules (correlation coefficient 0.475 and 0.527, p<0.05). Moreover, we found a correlation for both EMMPRIN and CyPA with CD68 (correlation coefficient 0.393 and 0.387, p<0.05) and CD3 (correlation coefficient 0.360 and 0.235, p<0.05). EMMPRIN is enhanced in both inflammatory and non inflammatory cardiomyopathies and can serve as a marker of myocardial remodeling. CyPA may represent a novel and specific marker for cardiac inflammation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Establishment and evaluation of extracorporeal circulation model in rats].

PubMed

Xie, Xiao-Jun; Tao, Kai-Yu; Tang, Meng-Lin; Du, Lei; An, Qi; Lin, Ke; Gan, Chang-Ping; Chen, You-Wen; Luo, Shu-Hua

2012-09-01

To establish an extracorporeal circulation (ECC) rat model, and evaluate the inflammatory response and organ injury induced in the model. SD rats were anesthetized and cannulated from right common carotid artery to left femoral vein to establish the bypass of extracorporeal circulation. Then the rats were randomly divided into ECC group and sham group. The rats in ECC group were subjected to extracorporeal circulation for 2 hours and then rest for 2 hours, while the rats in sham group were only observed for 4 hours without extracorporeal circulation. After that, blood routine examination, blood gas analysis, the measurement of pro-inflammatory factors in bronchoalveolar lavage fluid and lung tissue were performed to evaluate the lung injury induced by ECC. Circulating endothelial cells were also calculated by flow cytometry to assess the vascular endothelial injury. At 2 hours after ECC, red blood cell counts in both groups kept normal, while leukocyte and neutrophil counts, plasmatic tumor necrosis factor-a level and neutrophil elastase level, circulating endothelial cells in the rats of ECC group were significantly higher than those in sham group. Tumor necrosis factor-alpha in bronchoalveolar lavage fluid and water content in lung of the ECC rats were also significantly higher, while the oxygenation index was significantly lower. Neutrophil infiltration was also observed in lung tissues with increased thickness of alveolar membrane in ECC group. The ECC model established from right common carotid artery to left femoral vein in our study can successfully induce systemic inflammatory response, and acute lung injury associated with inflammation.

Investigating the Relationships Between Alcohol Consumption, Cannabis Use, and Circulating Cytokines: A Preliminary Analysis.

PubMed

Karoly, Hollis C; Bidwell, L Cinnamon; Mueller, Raeghan L; Hutchison, Kent E

2018-03-01

In recent years, human and animal studies have converged to support altered inflammatory signaling as a molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD. Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation. Thus, the impact of cannabis on inflammation in AUDs in humans warrants examination. We explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-8, and IL-1β in the blood. Among 66 regular drinkers (mean age = 30.08), we examined circulating cytokines and administered questionnaires assessing alcohol consumption and days of cannabis use over the past 90 days. We examined whether alcohol consumption, cannabis use, and gender were associated with changes in circulating cytokines, and whether there was a significant interaction between alcohol and cannabis use predicting blood levels of circulating cytokines. A positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1β. Follow-up moderation analyses indicated a cannabis by alcohol interaction predicting circulating IL-6, such that cannabis nonusers showed a stronger relationship between alcohol and IL-6 compared to cannabis users. These preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use. In addition, the present results provide data to inform future investigations, with the goal of ultimately leveraging knowledge of the role of inflammation in AUDs to develop more effective treatments focused on novel immune targets. Copyright © 2017 by the Research Society on Alcoholism.

[Association of age, inflammatory markers and subclinical atherosclerosis in subjects free from cardiovascular disease].

PubMed

Páramo, José A; Orbe, Josune; Beloqui, Oscar; Colina, Inmaculada; Benito, Alberto; Rodríguez, José A; Díez, Javier

2008-09-27

We assessed whether an independent association between inflammatory markers and age-related subclinical atherosclerosis could be found in subjects free from cardiovascular disease. Metabolic parameters, inflammatory and endothelial markers, such as high-sensitivity C-reactive protein, interleukin-6, fibrinogen and von Willebrand factor, as well as the carotid intima-media thickness were assessed in 890 asymptomatic subjects (mean age: 55 years; range: 20-80 years; 80% men) with cardiovascular risk factors. Subjects in the upper quartile (age 61-80 years) showed a significant increase of traditional risk factors, particularly arterial pressure and glucose levels (p < 0.01) as compared with lower quartiles. We also found a significant increase in the levels on inflammatory and endothelial markers (p < 0.001) and intima-media thickness (p < 0.001) in older adults. In the multivarate analysis, after adjustment for cardiovascular risk factors, intima-media thickness was independently associated with inflammation and endothelial dysfunction in older adults (p < 0.01). Besides age, systemic inflammation and vascular damage are associated with subclinical atherosclerosis in asymptomatic subjects. The age-related inflammatory profile may predispose to cardiovascular complications.

Targeting inflammation in diabetes: Newer therapeutic options

PubMed Central

Agrawal, Neeraj Kumar; Kant, Saket

2014-01-01

Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resistance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflammation.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. Interleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce inflammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabetes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory markers. Retinopathy drugs are used to target vascular endothelial growth factor, angiopoietin-2, various proteinases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapamycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, peroxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory therapies represent a potential approach for the therapy of diabetes and its complications. PMID:25317247

Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age

PubMed Central

Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Riera, Joan; Drobnic, Franchek; Tur, Josep Antoni; Pons, Antoni

2016-01-01

n-3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs). Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα) levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs), soluble Intercellular adhesion molecule 3 (sICAM3) and soluble L-selectin (sL-Selectin), and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group. PMID:27735833

Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age.

PubMed

Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Riera, Joan; Drobnic, Franchek; Tur, Josep Antoni; Pons, Antoni

2016-10-09

n -3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs). Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα) levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs), soluble Intercellular adhesion molecule 3 (sICAM3) and soluble L-selectin (sL-Selectin), and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group.

Biomarkers of sepsis

PubMed Central

2013-01-01

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults.

PubMed

Bortnick, Anna E; Bartz, Traci M; Ix, Joachim H; Chonchol, Michel; Reiner, Alexander; Cushman, Mary; Owens, David; Barasch, Eddy; Siscovick, David S; Gottdiener, John S; Kizer, Jorge R

2016-07-13

Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A 2 (LpPLA 2 ) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression. Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA 2 mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA 2 mass, 1.036 (1.006 to 1.066) and LpPLA 2 activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC. This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA 2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Metabolomic markers of fatigue: Association between circulating metabolome and fatigue in women with chronic widespread pain.

PubMed

Freidin, Maxim B; Wells, Helena R R; Potter, Tilly; Livshits, Gregory; Menni, Cristina; Williams, Frances M K

2018-02-01

Fatigue is a sensation of unbearable tiredness that frequently accompanies chronic widespread musculoskeletal pain (CWP) and inflammatory joint disease. Its mechanisms are poorly understood and there is a lack of effective biomarkers for diagnosis and onset prediction. We studied the circulating metabolome in a population sample characterised for CWP to identify biomarkers showing specificity for fatigue. Untargeted metabolomic profiling was conducted on fasting plasma and serum samples of 1106 females with and without CWP from the TwinsUK cohort. Linear mixed-effects models accounting for covariates were used to determine relationships between fatigue and metabolites. Receiver operating curve (ROC)-analysis was used to determine predictive value of metabolites for fatigue. While no association between fatigue and metabolites was identified in twins without CWP (n=711), in participants with CWP (n=395), levels of eicosapentaenoate (EPA) ω-3 fatty acid were significantly reduced in those with fatigue (β=-0.452±0.116; p=1.2×10 -4 ). A significant association between fatigue and two other metabolites also emerged when BMI was excluded from the model: 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), and C-glycosyltryptophan (p=1.5×10 -4 and p=3.1×10 -4 , respectively). ROC analysis has identified a combination of 15 circulating metabolites with good predictive potential for fatigue in CWP (AUC=75%; 95% CI 69-80%). The results of this agnostic metabolomics screening show that fatigue is metabolically distinct from CWP, and is associated with a decrease in circulating levels of EPA. Our panel of circulating metabolites provides the starting point for a diagnostic test for fatigue in CWP. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Gold Nanoparticle Based Platforms for Circulating Cancer Marker Detection

PubMed Central

Huang, Xiaohua; O'Connor, Ryan; Kwizera, Elyahb Allie

2017-01-01

Detection of cancer-related circulating biomarkers in body fluids has become a cutting-edge technology that has the potential to noninvasively screen cancer, diagnose cancer at early stage, monitor tumor progression, and evaluate therapy responses. Traditional molecular and cellular detection methods are either insensitive for early cancer intervention or technically costly and complicated making them impractical for typical clinical settings. Due to their exceptional structural and functional properties that are not available from bulk materials or discrete molecules, nanotechnology is opening new horizons for low cost, rapid, highly sensitive, and highly specific detection of circulating cancer markers. Gold nanoparticles have emerged as a unique nanoplatform for circulating biomarker detection owning to their advantages of easy synthesis, facile surface chemistry, excellent biocompatibility, and remarkable structure and environment sensitive optical properties. In this review, we introduce current gold nanoparticle-based technology platforms for the detection of four major classes of circulating cancer markers - circulating tumor cells, vesicles, nucleic acids, and proteins. The techniques will be summarized in terms of signal detection strategies. Distinctive examples are provided to highlight the state-of-the-art technologies that significantly advance basic and clinical cancer research. PMID:28217434

Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1

PubMed Central

Csiszar, Anna; Labinskyy, Nazar; Jimenez, Rosario; Pinto, John T.; Ballabh, Praveen; Losonczy, Gyorgy; Pearson, Kevin J.; de Cabo, Rafael; Ungvari, Zoltan

2009-01-01

Endothelial-dysfunction, oxidative stress and inflammation are associated with vascular aging and promote the development of cardiovascular-disease. Caloric restriction (CR) mitigates conditions associated with aging, but its effects on vascular dysfunction during aging remain poorly defined. To determine whether CR exerts vasoprotective effects in aging, aortas of ad libitum (AL) fed young and aged and CR-aged F344 rats were compared. Aging in AL-rats was associated with impaired acetylcholine-induced relaxation, vascular oxidative stress and increased NF-κB-activity. Lifelong CR significantly improved endothelial function, attenuated vascular ROS production, inhibited NF-κB activity and down-regulated inflammatory genes. To elucidate the role of circulating factors in mediation of the vasoprotective effects of CR, we determined whether sera obtained from CR-animals can confer anti-oxidant and anti-inflammatory effects in cultured coronary-arterial endothelial cells (CAECs), mimicking the effects of CR. In CAECs cultured in the presence of AL-serum TNFα elicited oxidative-stress, NF-κB-activation and inflammatory gene expression. By contrast, treatment of CAECs with CR-serum attenuated TNFα-induced ROS generation and prevented NF-κB-activation and induction of inflammatory genes. siRNA-knockdown of SIRT1 mitigated the anti-oxidant and anti-inflammatory effects of CR-serum. CR exerts anti-oxidant and anti-inflammatory vascular effects, which are likely mediated by circulating factors, in part, via a SIRT1-dependent pathway. PMID:19549533

Inflammatory and nutritional statuses of patients submitted to resection of gastrointestinal tumors.

PubMed

Fruchtenicht, Ana Valéria Gonçalves; Poziomyck, Aline Kirjner; Reis, Audrey Machado Dos; Galia, Carlos Roberto; Kabke, Georgia Brum; Moreira, Luis Fernando

2018-01-01

to evaluate the association between the nutritional and the inflammatory statuses of patients with cancer of the gastrointestinal tract undergoing surgical resection and to identify predictors of mortality in these patients. we conducted a prospective study of 41 patients with gastrointestinal tract cancer submitted to surgery between October 2012 and December 2014. We evaluated the nutritional status by subjective and objective methods. We assessed the inflammatory response and prognosis using the modified Glasgow Prognostic Score (mGPS), Neutrophil/Lymphocyte Ratio (NLR), Onodera Prognostic Nutritional Index (mPNI), Inflammatory-Nutritional Index (INI) and C-Reactive Protein/Albumin ratio (mPINI). half of the patients were malnourished and 27% were at nutritional risk. There was a positive association between the percentage of weight loss (%WL) and the markers NLR (p=0.047), mPINI (p=0.014) and INI (p=0.015). Serum albumin levels (p=0.015), INI (p=0.026) and mPINI (p=0.026) were significantly associated with the PG-SGA categories. On multivariate analysis, albumin was the only inflammatory marker independently related to death (p=0.004). inflammatory markers were significantly associated with malnutrition, demonstrating that the higher the inflammatory response, the worse the PG-SGA (B and C) scores and the higher the %WL in these patients. However, further studies aimed at improving surgical outcomes and determining the role of these markers as predictors of mortality are required.

Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule.

PubMed

Witek, Małgorzata A; Aufforth, Rachel D; Wang, Hong; Kamande, Joyce W; Jackson, Joshua M; Pullagurla, Swathi R; Hupert, Mateusz L; Usary, Jerry; Wysham, Weiya Z; Hilliard, Dawud; Montgomery, Stephanie; Bae-Jump, Victoria; Carey, Lisa A; Gehrig, Paola A; Milowsky, Matthew I; Perou, Charles M; Soper, John T; Whang, Young E; Yeh, Jen Jen; Martin, George; Soper, Steven A

2017-01-01

Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges.

Muscle-specific deletion of SOCS3 increases the early inflammatory response but does not affect regeneration after myotoxic injury.

PubMed

Swiderski, Kristy; Thakur, Savant S; Naim, Timur; Trieu, Jennifer; Chee, Annabel; Stapleton, David I; Koopman, René; Lynch, Gordon S

2016-01-01

Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade is a key mediator of inflammatory cytokine action, and signaling via this pathway is increased in muscles with aging. As a negative regulator of JAK/STAT signaling, a key mediator of myogenic proliferation and differentiation, altered expression of suppressor of cytokine signaling (SOCS3) is likely to have important consequences for muscle regeneration. To model this scenario, we investigated the effect of SOCS3 deletion within mature muscle fibers on injury and repair. We tested the hypothesis that reduced SOCS3 function would alter the inflammatory response and impair muscle regeneration after myotoxic injury. Mice with a specific deletion of SOCS3 within mature skeletal muscle fibers were used to assess the effect of SOCS3 deletion on muscle injury and repair. Twelve-week-old or 24-month-old SOCS3 muscle-specific knockout (SOCS3 MKO) mice and littermate controls were either left uninjured or injured with a single injection of notexin (10 μg/ml) into the right tibialis anterior (TA) muscle. At 1, 2, 3, 5, 7, or 14 days post-injury, the right TA muscle was excised and subjected to histological, western immunoblotting, and gene expression analyses. Force production and fatigue were assessed in uninjured muscles and at 7 days post-notexin injury. In uninjured muscles, SOCS3 deletion decreased force production during fatigue but had no effect on the gross or histological appearance of the TA muscles. After notexin injury, deletion of SOCS3 increased STAT3 phosphorylation at day 1 and increased the mRNA expression of the inflammatory cytokine TNF-α , and the inflammatory cell markers F4/80 and CD68 at day 2. Gene expression analysis of the regeneration markers Pax7 , MyoD , and Myogenin indicated SOCS3 deletion had no effect on the progression of muscle repair after notexin injury. Inflammation and regeneration were also unchanged in the muscles of 24-month-old SOCS3 MKO mice compared with control. Loss of SOCS3 expression in mature muscle fibers increased the inflammatory response to myotoxic injury but did not impair muscle regeneration in either adult or old mice. Therefore, reduced SOCS3 expression in muscle fibers is unlikely to underlie impaired muscle regeneration. Further investigation into the role of SOCS3 in other cell types involved in muscle repair is warranted.

Protein S is protective in pulmonary fibrosis.

PubMed

Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

2016-08-01

Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar epithelial cells in vitro. Conclusions These observations suggest clinical relevance and a protective role of protein S in pulmonary fibrosis. © 2016 International Society on Thrombosis and Haemostasis.

Novel protective role of kallistatin in obesity by limiting adipose tissue low grade inflammation and oxidative stress.

PubMed

Frühbeck, Gema; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Valentí, Víctor; Moncada, Rafael; Becerril, Sara; Unamuno, Xabier; Silva, Camilo; Salvador, Javier; Catalán, Victoria

2018-04-18

Kallistatin plays an important role in the inhibition of inflammation, oxidative stress, fibrosis and angiogenesis. We aimed to determine the impact of kallistatin on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and oxidative stress. Samples obtained from 95 subjects were used in a case-control study. Circulating concentrations and expression levels of kallistatin as well as key inflammation, oxidative stress and extracellular matrix remodelling-related genes were analyzed. Circulating kallistatin concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB). The impact of kallistatin on lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-α-mediated inflammatory as well as oxidative stress signalling pathways was evaluated. We show that the reduced (P < 0.00001) circulating levels of kallistatin in obese patients increased (P < 0.00001) after RYGB. Moreover, gene expression levels of SERPINA4, the gene coding for kallistatin, were downregulated (P < 0.01) in the liver from obese subjects with non-alcoholic fatty liver disease. Additionally, we revealed that kallistatin reduced (P < 0.05) the expression of inflammation-related genes (CCL2, IL1B, IL6, IL8, TNFA, TGFB) and, conversely, upregulated (P < 0.05) mRNA levels of ADIPOQ and KLF4 in human adipocytes in culture. Kallistatin inhibited (P < 0.05) LPS- and TNF-α-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Furthermore, kallistatin also blocked (P < 0.05) TNF-α-mediated lipid peroxidation as well as NOX2 and HIF1A expression while stimulating (P < 0.05) the expression of SIRT1 and FOXO1. These findings provide, for the first time, evidence of a novel role of kallistatin in obesity and its associated comorbidities by limiting adipose tissue inflammation and oxidative stress. Copyright © 2018 Elsevier Inc. All rights reserved.

[The present and future state of minimized extracorporeal circulation].

PubMed

Meng, Fan; Yang, Ming

2013-05-01

Minimized extracorporeal circulation improved in the postoperative side effects of conventional extracorporeal circulation is a kind of new extracorporeal circulation. This paper introduces the principle, characteristics, applications and related research of minimized extracorporeal circulation. For the problems of systemic inflammatory response syndrome and limited assist time, the article proposes three development direction including system miniaturization and integration, pulsatile blood pump and the adaptive control by human parameter identification.

Metabolites associated with circulating interleukin-6 in older adults

USDA-ARS?s Scientific Manuscript database

Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in ...

Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up.

PubMed

Berg, Jan; Kottwitz, Jan; Baltensperger, Nora; Kissel, Christine K; Lovrinovic, Marina; Mehra, Tarun; Scherff, Frank; Schmied, Christian; Templin, Christian; Lüscher, Thomas F; Heidecker, Bettina; Manka, Robert

2017-11-01

There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. © 2017 American Heart Association, Inc.

Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.

PubMed

Aragon, Mario J; Topper, Lauren; Tyler, Christina R; Sanchez, Bethany; Zychowski, Katherine; Young, Tamara; Herbert, Guy; Hall, Pamela; Erdely, Aaron; Eye, Tracy; Bishop, Lindsey; Saunders, Samantha A; Muldoon, Pretal P; Ottens, Andrew K; Campen, Matthew J

2017-03-07

Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 µm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.

Endogenous hormones, inflammation, and body size in premenopausal Mexican women: results from the Mexican Teachers' Cohort (MTC, ESMaestras).

PubMed

Rinaldi, Sabina; Biessy, Carine; de la Luz Hernandez, Maria; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

2015-03-01

Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women. We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity. Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index. The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.

Usefulness of elevated red cell distribution width for predicting systemic inflammatory response syndrome after extracorporeal circulation.

PubMed

Özeren, M; Aytaçoğlu, B; Vezir, Ö; Karaca, K; Akın, R; Sucu, N

2015-10-01

Cardiac surgical operations performed by using extracorporeal circulation (ECC) lead to a systemic inflammatory response (SIR). Sometimes SIR may turn into a severe state, the systemic inflammatory response syndrome (SIRS) that usually has a poor outcome with no specific clinical tools described for its prediction. Red cell distribution width (RDW) is a routine hematological parameter. It has been proposed as a marker of morbidity and mortality in various clinical conditions. We aimed to investigate the relationship between high RDW and SIRS which is triggered by ECC. Eleven hundred consecutive patients who underwent elective heart surgery with the use of ECC were retrospectively analyzed. A total of 19 patients fulfilled the described SIRS criteria and 20 consecutive patients were selected as the control group. RDW and other laboratory parameters, preoperative clinical status, operative data and postoperative data were compared between the SIRS and the control groups. Baseline characteristics of the patient groups were similar. Significant mortality was found in the SIRS group; 18 (94.73%) patients and 2 (10%) patients in the control group (p < 0.002). RDW was found to be significantly higher in the SIRS group vs the control group (15.02 ± 2.03 vs 13.01 ± 1.93, respectively, p < 0.003). Multiple logistic regression analyses showed an association between high RDW levels and SIRS development (OR for RDW levels exceeding 13.5%; 95% confidence limits of 1.0-1.3; p < 0.04). Total operation time and the need for inotropic support were also found to be significant against the SIRS group (p = 0.049). Increased RDW was significantly associated with increased risk of SIRS after ECC. The results of this study suggest that paying attention to RDW might provide valuable clinical information for predicting SIRS development among patients who are candidates for open heart surgery, without incurring additional costs. © The Author(s) 2015.

Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats.

PubMed

Brahma Naidu, Parim; Uddandrao, V V Sathibabu; Ravindar Naik, Ramavat; Suresh, Pothani; Meriga, Balaji; Begum, Mustapha Shabana; Pandiyan, Rajesh; Saravanan, Ganapathy

2016-01-05

Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6). The rats were treated orally with gingerol (75 mg kg(-1)) once daily for 30 days with a lorcaserin-treated group (10 mg kg(-1)) included for comparison. Changes in body weight, glucose, insulin resistance and expressions of lipid marker enzymes and inflammatory markers in tissues were observed in experimental rats. The administration of gingerol resulted in a significant reduction in body weight gain, glucose and insulin levels, and insulin resistance, which altered the activity, expressions of lipid marker enzymes and inflammatory markers. It showed that gingerol had significantly altered these parameters when compared with HFD control rats. This study confirms that gingerol prevents HFD-induced hyperlipidemia by modulating the expression of enzymes important to cholesterol metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Is hepcidin a new cardiovascular risk marker in polycystic ovary syndrome?

PubMed

Gözdemir, Elif; Kaygusuz, Ikbal; Kafalı, Hasan

2013-01-01

Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities and carries a number of cardiovascular risk factors. Low-grade chronic inflammation has been thought to play a role in the pathogenesis of atherosclerosis and PCOS patients have an increased rate of subclinical inflammation. In the present study, considering the major role that hepcidin plays in the regulation of iron metabolism and as an inflammatory marker, we investigated hepcidin in PCOS patients and its role in predicting cardiovascular disease (CVD) development. Forty patients with PCOS and 40 age- and body mass index-matched healthy controls were included in the study. Iron metabolites, insulin resistance (IR), inflammatory markers and hepcidin levels were analyzed. IR parameters, inflammatory markers, iron parameters and hepcidin levels were similar between the PCOS and control groups. While the inflammatory markers were significantly high in the overweight and obese PCOS subgroup, the hepcidin levels were also high but this elevation was not statistically significant. Obesity is the principle mechanism of chronic inflammation and IR in PCOS patients. C-reactive protein and interleukin-6 should be used to predict and follow the risk of CVD development in PCOS cases. Hepcidin may be used as an additional marker in the follow-up of PCOS patients in the future. Copyright © 2013 S. Karger AG, Basel.

Kinetics of common inflammatory biomarkers in postoperative course after congenital heart defects procedures with extracorporeal circulation in children.

PubMed

Haponiuk, Ireneusz; Jaworski, Radosław; Paczkowski, Konrad; Chojnicki, Maciej; Steffens, Mariusz; Szofer-Sendrowska, Aneta; Gierat-Haponiuk, Katarzyna; Kwaśniak, Ewelina; Paśko-Majewska, Marta; Leszczyńska, Katarzyna; Zieliński, Jacek; Szymanowicz, Wiktor

2018-02-05

The extracorporeal circulation is associated with systemic inflammatory response syndrome. Therefore, the diagnosis of infection should be differenced from typical postoperative course. Evaluation of kinetics of inflammatory biomarkers in children in the first days after cardiac surgery with extracorporeal circulation. Prospective data collection from 51 consecutive children referred for surgical treatment [the Institution], between February 2015 and August 2015. Blood samples were collected in the first, second and third postoperative days and send to institutional laboratory for routine lab-tests: white blood cells count, serum C-reactive protein and procalcitonin concentration. The highest levels of procalcitonin were in the first postoperative day (median 3,53 ng/mL), although the peak values of C-reactive protein concentration and white blood cells count were in the second postoperative day (as follows 96mg/L and 17,3 G/L). In the group of patients with foreign material implantation (Contegra® or Gore-Tex®), the higher values of procalcitonin concentration and white blood cells count were measured in the further postoperative days. Kinetics of analyzed inflammatory biomarkers in the first days after cardiac surgery for congenital heart disease in children have different characteristics. The knowledge about inflammatory biomarkers' kinetics could be useful in determining the possibility of evolving infections in the early postoperative period.

Marathon running increases circulating endothelial- and thrombocyte-derived microparticles.

PubMed

Schwarz, Viktoria; Düsing, Philip; Liman, Thomas; Werner, Christian; Herm, Juliane; Bachelier, Katrin; Krüll, Matthias; Brechtel, Lars; Jungehulsing, Gerhard J; Haverkamp, Wilhelm; Böhm, Michael; Endres, Matthias; Haeusler, Karl Georg; Laufs, Ulrich

2018-02-01

Background Acute vascular effects of high intensity physical activity are incompletely characterized. Circulating microparticles are cellular markers for vascular activation and damage. Methods Microparticles were analysed in 99 marathon runners (49 ± 6 years, 22% female) of the prospective Berlin Beat of Running study. Blood samples were taken within three days before, immediately after and within two days after the marathon run. Endothelial-derived microparticles were labelled with CD144, CD31 and CD62E, platelet-derived microparticles with CD62P and CD42b, leukocyte-derived microparticles with CD45 and monocyte-derived microparticles with CD14. Results Marathon running induced leukocytosis (5.9 ± 0.1 to 14.8 ± 0.3 10 9 /l, p < 0.0001) and increased platelet counts (239 ± 4.6 to 281 ± 5.9 10 9 /l, p < 0.0001) immediately after the marathon. Blood monocytes increased and lymphocytes decreased after the run ( p < 0.0001). Endothelial-derived microparticles were acutely increased ( p = 0.008) due to a 23% increase of apoptotic endothelial-derived microparticles ( p = 0.007) and returned to baseline within two days after the marathon. Thrombocyte-derived microparticles acutely increased by 38% accompanied by an increase in activated and apoptotic thrombocyte-derived microparticles ( p ≤ 0.0001) each. Both monocyte- and leukocyte-derived microparticles were decreased immediately after marathon run ( p < 0.0001) and remained below baseline until day 2. Troponin T increased from 12 to 32 ng/l ( p < 0.0001) immediately after the run and returned to baseline after two days. Conclusion Circulating apoptotic endothelial- and thrombocyte-derived microparticles increased after marathon running consistent with an acute pro-thrombotic and pro-inflammatory state. Exercise-induced vascular damage reflected by microparticles could indicate potential mechanisms of post-exertional cardiovascular complications. Further studies are warranted to investigate microparticles as markers to identify individuals prone to such complications.

Prospective randomized comparison of coronary bypass grafting with minimal extracorporeal circulation system (MECC) versus off-pump coronary surgery.

PubMed

Mazzei, Valerio; Nasso, Giuseppe; Salamone, Giovanni; Castorino, Filippo; Tommasini, Antonello; Anselmi, Amedeo

2007-10-16

We aimed to evaluate the clinical results and biocompatibility of the minimal extracorporeal circulation system (MECC) compared with off-pump coronary revascularization (OPCABG). In a prospective randomized study, 150 patients underwent coronary surgery with the use of MECC and 150 underwent OPCABG. End points were (1) circulating markers of inflammation and organ injury, (2) operative results, and (3) outcome at 1-year follow-up. Operative mortality and morbidity were comparable between the groups. Release of inflammatory markers was similar between groups at all time points (peak interleukin-6 167.2+/-13.5 versus 181+/-6.5 pg/mL, P=0.14, OPCABG versus MECC group, respectively). Peak creatine kinase was 419.3+/-103.5 versus 326+/-84.2 mg/dL (P=0.28), and peak S-100 protein was 0.13+/-0.08 versus 0.29+/-0.1 pg/mL (P=0.058, OPCABG versus MECC group, respectively). Length of hospital stay and use of blood products were similar between groups. Two cases of angina recurrence at 1 year in the MECC group were observed versus 5 cases observed in the OPCABG group (P=0.44). A residual perfusion defect at myocardial nuclear scan was less frequent among patients in the MECC group (3 versus 9 cases, P=0.14; odds ratio 0.32, 95% confidence interval 0.07 to 1.32). Six (OPCABG group) versus 3 (MECC group) coronary grafts were occluded or severely stenotic at 1 year (P=0.33, odds ratio 0.47, 95% confidence interval 0.09 to 2.14). Clinical results of coronary revascularization with MECC are optimal when this procedure is performed by experienced teams. Postoperative morbidity is comparable to that with OPCABG. MECC is associated with little pump-related systemic and organ injury. It may achieve the benefits of OPCABG (less morbidity in high-risk patients) while facilitating complete revascularization in the case of complex lesions unsuitable for OPCABG.

CD31+ Cells From Peripheral Blood Facilitate Bone Regeneration in Biologically Impaired Conditions Through Combined Effects on Immunomodulation and Angiogenesis.

PubMed

Sass, F Andrea; Schmidt-Bleek, Katharina; Ellinghaus, Agnes; Filter, Sebastian; Rose, Alexander; Preininger, Bernd; Reinke, Simon; Geissler, Sven; Volk, Hans-Dieter; Duda, Georg N; Dienelt, Anke

2017-05-01

Controlled revascularization and inflammation are key elements regulating endogenous regeneration after (bone) tissue trauma. Peripheral blood-derived cell subsets, such as regulatory T-helper cells and circulating (endothelial) progenitor cells, respectively, can support endogenous tissue healing, whereas effector T cells that are associated with an aged immune system can hinder bone regeneration. CD31 is expressed by diverse leukocytes and is well recognized as a marker of circulating endothelial (precursor) cells; however, CD31 is absent from the surface of differentiated effector T cells. Thus, we hypothesized that by separating the inhibitory fractions from the supportive fractions of circulating cells within the peripheral blood (PB) using the CD31 marker, bone regeneration in biologically compromised conditions, such as those observed in aged patients, could be improved. In support of our hypothesis, we detected an inverse correlation between CD31+ cells and effector T cells in the hematomas of human fracture patients, dependent on the age of the patient. Furthermore, we demonstrated the regenerative capacity of human PB-CD31+ cells in vitro. These findings were translated to a clinically relevant rat model of impaired bone healing. The transplantation of rat PB-CD31+ cells advanced bone tissue restoration in vivo and was associated with an early anti-inflammatory response, the stimulation of (re)vascularization, and reduced fibrosis. Interestingly, the depletion or enrichment of the highly abundant CD31+/14+ monocytes from the mixed CD31+ cell population diminished tissue regeneration at different levels, suggesting combined effects within the PB-CD31+ subsets. In summary, an intraoperative enrichment of PB-CD31+ cells might be a novel option to facilitate endogenous regeneration under biologically impaired situations by supporting immunomodulation and vascularization. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein-4

PubMed Central

Phillips, Amy

2014-01-01

With a more sedentary population comes growing rates of obesity and increased type 2 diabetes mellitus (T2DM) risk. Exercise generally induces positive changes in traditional T2DM risk markers such as lipids, glucose tolerance, and insulin sensitivity; however alterations in concentrations of many circulating cytokines and their respective receptors are also becoming apparent. These cytokines may be early-response health risk factors otherwise overlooked in traditional T2DM risk marker analysis. Plasma levels of two adipocyte-originating cytokines, adiponectin and retinol binding protein 4 (RBP-4), alter following exercise. Adiponectin has anti-inflammatory, anti-atherosclerotic, and anti-insulin resistance roles and its secretion increases with physical activity, whilst elevated RBP-4 leads to increased insulin resistance, and secretion decreases with increasing physical activity; thus these plasma adipokine levels alter favourably following exercise. Although current data are limited, they do suggest that the more intense the exercise, the greater the positive effect on plasma RBP-4 levels, whilst lower intensity aerobic exercise may positively improve adiponectin concentrations. Therefore short-duration, high intensity training may provide a time-efficient alternative to the recommended 150 min moderate aerobic exercise per week in providing positive changes in RBP-4 and other traditional T2DM risk markers and due to increased compliance give greater health benefits over the longer term. PMID:26464853

Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice

PubMed Central

Wang, Xianfeng; Buechler, Nancy L.; Martin, Ayana; Wells, Jonathan; Yoza, Barbara; McCall, Charles E.; Vachharajani, Vidula

2016-01-01

Objective Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis. Methods Sepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis. Results We observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65. Conclusion SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may provide a novel treatment target for obesity with sepsis. PMID:27500833

Relationships of inflammatory and haemostatic markers with social class: results from a population-based study of older men.

PubMed

Ramsay, Sheena; Lowe, Gordon D O; Whincup, Peter H; Rumley, Ann; Morris, Richard W; Wannamethee, S Goya

2008-04-01

Haemostatic and inflammatory markers have been hypothesised to mediate the relationship of social class and cardiovascular disease (CVD). We investigated whether a range of inflammatory/haemostatic markers are associated with social class independent of chronic diseases and behavioural risk factors in a population-based sample of 2682 British men aged 60-79 without a physician diagnosis of CVD, diabetes or musculoskeletal disease requiring anti-inflammatory medications. Men in lower social classes had higher mean levels of C-reactive protein, fibrinogen, interleukin-6, white blood cell count, von Willebrand factor (vWF), factor VIII, activated protein C (APC) resistance, plasma viscosity, fibrin D-dimer and platelet count, compared to higher social class groups; but not of tissue plasminogen activator antigen, haematocrit or activated partial prothrombin time. After adjustment for behavioural risk factors (smoking, alcohol, physical activity and body mass), the associations of social class with vWF, factor VIII, APC resistance, plasma viscosity, and platelet count though weakened, remained statistically significant, while those of other markers were considerably attenuated. In this study of older men without CVD, the social gradient in inflammatory and haemostatic markers was substantially explained by behavioural risk factors. The effect of socio-economic gradient on the factor VIII-vWF complex, APC resistance, plasma viscosity and platelet count merits further study.

Vascular and Inflammatory Factors in the Pathophysiology of Blast-Induced Brain Injury

PubMed Central

Elder, Gregory A.; Gama Sosa, Miguel A.; De Gasperi, Rita; Stone, James Radford; Dickstein, Dara L.; Haghighi, Fatemeh; Hof, Patrick R.; Ahlers, Stephen T.

2015-01-01

Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role for a thoracically mediated effect of blast; whereby, pressure waves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI. PMID:25852632

Smoking, COPD and 3-Nitrotyrosine Levels of Plasma Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Hongjun; Webb-Robertson, Bobbie-Jo M.; Peterson, Elena S.

BACKGROUND: Nitric oxide is a physiologically regulator of endothelial function and hemodynamics. Oxidized products of nitric oxide can form nitrotyrosine, which is a marker of nitrative stress. Cigarette smoking decreases exhaled nitric oxide, and the underlying mechanism may be important in the cardiovascular toxicity of cigarette smoke, although it is not clear if this effect results from decreased nitric oxide production or oxidation of nitric oxide to reactive, nitrating, species. These processes would be expected to have opposite effects on nitrotyrosine levels, a marker of nitrative stress. OBJECTIVE: In this study, we determine the effects of smoking and chronic obstructivemore » pulmonary disease (COPD) on circulating levels of nitrotyrosine, and thereby gain insight into the processes regulating nitrotyrosine formation. METHODS: A custom antibody microarray platform was used to analyze the levels of 3-nitrotyrosine modifications on 24 proteins in plasma. Plasma samples from 458 individuals were analyzed. RESULTS: Nitrotyrosine levels in circulating proteins were uniformly reduced in smokers but increased in COPD patients. We also observed a persistent suppression of nitrotyrosine in former smokers. CONCLUSIONS: Smoking broadly suppresses the levels of 3-nitrotyrosine in plasma proteins, suggesting that cigarette smoke suppresses endothelial nitric oxide production. In contrast, the increase in nitrotyrosine levels in COPD patients most likely results from inflammatory processes. This study provides the first evidence that smoking has irreversible effects on endothelial production of nitric oxide, and provides insight into how smoking could induce a loss of elasticity in the vasculature and a long-term increase in the risk of cardiovascular disease.« less

The Effects of Ramadan Fasting on Body Composition, Blood Pressure, Glucose Metabolism, and Markers of Inflammation in NAFLD Patients: An Observational Trial.

PubMed

Aliasghari, Fereshteh; Izadi, Azimeh; Gargari, Bahram Pourghassem; Ebrahimi, Sara

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and is a serious global health problem. Regarding the increasing prevalence of NAFLD, finding various strategies to prevent and manage the disease is of great importance. The aim of this study was to determine the effects of caloric restriction during Ramadan fasting on anthropometric indices, fasting glucose, plasma insulin, insulin resistance, and inflammatory cytokines (C-reactive protein and interleukin 6) in patients with NAFLD. We conducted this study with 83 patients with NAFLD, 42 of whom decided to fast and 41 controls who decided not to fast for Ramadan, between June 18 and July 17, 2015. Anthropometric parameters were measured and a sample of venous blood was obtained for biochemical assays before and after Ramadan. There was a significant decrease in all anthropometric parameters as well as fasting glucose, plasma insulin, and insulin resistance. Relative to the nonfasting group, fasting significantly reduced circulating inflammatory, but changes in blood pressure after Ramadan were not significant. This study shows significant effects on parameters during Ramadan fasting such as anthropometric indices, fasting glucose, plasma insulin, and inflammatory cytokines in patients with NAFLD. The results of this study suggest that Ramadan fasting may be useful to improve NAFLD, so further studies are needed in this area.

Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study.

PubMed

García-Bailo, Bibiana; Roke, Kaitlin; Mutch, David M; El-Sohemy, Ahmed; Badawi, Alaa

2012-11-16

Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D was not associated with altered concentrations of any inflammatory biomarkers. These findings suggest that α-tocopherol, but not ascorbic acid or 25(OH)D, is inversely associated with inflammation in healthy young adults.

Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy.

PubMed

Campos, Raquel Munhoz da Silveira; Masquio, Deborah Cristina Landi; Corgosinho, Flávia Campos; Carvalho-Ferreira, Joana Pereira de; Molin Netto, Bárbara Dal; Clemente, Ana Paula Grotti; Tock, Lian; Tufik, Sergio; Mello, Marco Túlio de; Dâmaso, Ana Raimunda

2018-05-17

Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.

SOURCE APPORTIONMENT OF FINE PARTICULATE MATTER IN THE U.S. AND ASSOCIATIONS WITH LUNG INFLAMMATORY MARKERS IL -8, COX -2 AND HO -1

EPA Science Inventory

Associations are well established between particulate matter (PM) and increased human mortality and morbidity. The association between fine PM sources and lung inflammatory markers IL-8, COX-2, and HO-1 was evaluated in this study.

Biomarkers Associated with Cognitive Impairment in Treated Cancer Patients: Potential Predisposition and Risk Factors

PubMed Central

Castel, Hélène; Denouel, Angeline; Lange, Marie; Tonon, Marie-Christine; Dubois, Martine; Joly, Florence

2017-01-01

Purpose: Cognitive impairment in cancer patients induced, at least in part, by treatment are frequently observed and likely have negative impacts on patient quality of life. Such cognitive dysfunctions can affect attention, executive functions, and memory and processing speed, can persist after treatment, and their exact causes remain unclear. The aim of this review was to create an inventory and analysis of clinical studies evaluating biological markers and risk factors for cognitive decline in cancer patients before, during, or after therapy. The ultimate objectives were to identify robust markers and to determine what further research is required to develop original biological markers to enable prevention or adapted treatment management of patients at risk. Method: This review was guided by the PRISMA statement and included a search strategy focused on three components: “cognition disorders,” “predictive factors”/“biological markers,” and “neoplasms,” searched in PubMed since 2005, with exclusion criteria concerning brain tumors, brain therapy, and imaging or animal studies. Results: Twenty-three studies meeting the criteria were analyzed. Potential associations/correlations were identified between cognitive impairments and specific circulating factors, cerebral spinal fluid constituents, and genetic polymorphisms at baseline, during, and at the end of treatment in cancer populations. The most significant results were associations between cognitive dysfunctions and genetic polymorphisms, including APOE-4 and COMT-Val; increased plasma levels of the pro-inflammatory cytokine, IL-6; anemia; and hemoglobin levels during chemotherapy. Plasma levels of specific hormones of the hypothalamo-pituitary-adrenal axis are also modified by treatment. Discussion: It is recognized in the field of cancer cognition that cancer and comorbidities, as well as chemotherapy and hormone therapy, can cause persistent cognitive dysfunction. A number of biological circulating factors and genetic polymorphisms, can predispose to the development of cognitive disorders. However, many predictive factors remain unproven and discordant findings are frequently reported, warranting additional clinical and preclinical longitudinal cohort studies, with goals of better characterization of potential biomarkers and identification of patient populations at risk and/or particularly deleterious treatments. Research should focus on prevention and personalized cancer management, to improve the daily lives, autonomy, and return to work of patients. PMID:28377717

Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.

Background: Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods: A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed bymore » ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results: After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions: Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. - Highlights: • Cadmium is a toxic proinflammatory, proatherosclerotic metal. • Soluble urokinase-type plasminogen activator receptor (suPAR) in plasma is a promising proinflammatory marker of atherosclerosis. • Blood cadmium and plasma suPAR were measured in a cohort of 4648 Swedish men and women. • Blood cadmium was positively associated with plasma suPAR, also in never smokers.« less

Evaluation of circulating markers of hepatic apoptosis and inflammation in obese children with and without obstructive sleep apnea.

PubMed

Alkhouri, Naim; Kheirandish-Gozal, Leila; Matloob, Ammar; Alonso-Álvarez, María Luz; Khalyfa, Abdelnaby; Terán-Santos, Joaquin; Okwu, Vera; Lopez, Rocio; Gileles-Hillel, Alex; Dweik, Raed; Gozal, David

2015-09-01

Hepatocyte apoptosis and macrophage activation contribute to the disease progression of nonalcoholic fatty liver disease (NAFLD). Obstructive sleep apnea (OSA) in obese children is associated with the severity of NAFLD. The aim of this study was to evaluate plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), cytokeratin 18 (CK18) (markers of apoptosis), and soluble CD163 (sCD163) (marker of macrophage activation) in obese children with and without OSA. Consecutive obese children who were evaluated for OSA were recruited. The diagnosis of OSA was made using overnight polysomnography (PSG). Fasting blood samples were used to determine plasma CK18, sFas, sFasL, and sCD163 levels using specific sandwich enzyme-linked immunosorbent assay (ELISA). Fifty-eight subjects were included in the analysis with a mean age of 8.9 ± 3.2 years and a mean body mass index (BMI) z-score of 2.4 ± 0.49. Circulating sFas and sFasL levels were significantly lower in subjects with mild and severe OSA compared with those without OSA (p < 0.005 for both). In addition, sCD163 levels increased with an increasing severity of OSA (no OSA = 1.6 ± 0.25 mg/L, mild OSA = 2.3 ± 0.45, and severe OSA = 3.0 ± 0.52; p < 0.001), and they correlated with the apnea-hypopnea index (AHI) [rho (95% confidence interval, CI) of 0.71 (0.41, 1.00), p-value <0.001]. In six patients with severe OSA from whom samples were taken before and after tonsillectomy, the sCD163 level decreased significantly after treatment, and there was a trend toward an increase in sFasL. Markers of apoptosis and macrophage activation are altered in obese children with OSA, indicating increased apoptotic and inflammatory pressures. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Supragingival Irrigation with Aerosolized 0.5% Hydrogen Peroxide on Clinical Periodontal Parameters, Markers of Systemic Inflammation, and Morphology of Gingival Tissues in Patients with Periodontitis

PubMed Central

Žekonis, Gediminas; Žekonis, Jonas; Gleiznys, Alvydas; Noreikienė, Viktorija; Balnytė, Ingrida; Šadzevičienė, Renata; Narbutaitė, Julija

2016-01-01

Background Various studies have shown that non-surgical periodontal treatment is correlated with reduction in clinical parameters and plasma levels of inflammatory markers. The aim of this study was to evaluate the effect of long-term weekly supragingival irrigations with aerosolized 0.5% hydrogen peroxide as maintenance therapy followed by non-surgical periodontal treatment on clinical parameters, plasma levels of inflammatory markers, and morphological changes in gingival tissues of patients with periodontitis. Material/Methods In total, 43 patients with chronic periodontitis were randomly allocated to long-term maintenance therapy. The patients’ periodontal status was assessed using clinical parameters of approximal plaque index, modified gingival index, bleeding index, pocket probing depth, and plasma levels of inflammatory markers (high-sensitivity C-reactive protein and white blood cell count) at baseline and after 1, 2, and 3 years. The morphological status of gingival tissues (immediately after supragingival irrigation) was assessed microscopically. Results Complete data were obtained on 34 patients. A highly statistically significant and consistent reduction was observed in all long-term clinical parameters and plasma levels of inflammatory markers. Morphological data showed abundant spherical bubbles in gingival tissues. Conclusions 1. The present study showed that non-surgical periodontal treatment with long-term weekly supragingival irrigations with aerosolized 0.5% hydrogen peroxide improved clinical periodontal status and plasma levels of inflammatory markers and may be a promising method in periodontology. 2. We found that supragingival irrigation with aerosolized 0.5% hydrogen peroxide created large numbers of spherical bubbles in gingival tissues. PMID:27743448

Effects of resistance training at different loads on inflammatory markers in young adults.

PubMed

Forti, Louis Nuvagah; Van Roie, Evelien; Njemini, Rose; Coudyzer, Walter; Beyer, Ingo; Delecluse, Christophe; Bautmans, Ivan

2017-03-01

Suppressing inflammaging at an early stage in life via exercise might prevent chronic diseases later in life. The aim was to investigate the influence of resistance training at different external loads on inflammatory markers in healthy young adults. Serum was collected for basal levels of cytokines (IL-1beta, IL-6, IL-8, sTNFR1, IL-1RA, IL-10 and GM-CSF) before and after 9 weeks exercise from 36 young (22 ± 2 years) healthy subjects who were randomized to three times weekly supervised resistance training at either HI max (n = 12, 1 × 10-12 repetitions at 80% 1RM), LO (n = 12, 1 × 10-12 repetitions at 40% 1RM), or LO max (n = 12, 1 × 10-12 repetitions at 40% 1RM preceded by 60 repetitions at 20-25% 1RM) respectively. Overall, IL-8 increased (p < 0.001) and IL-6 decreased (p = 0.001) after training, but no significant time*group interaction was found (respectively, p = 0.283 and p = 0.058 for IL-8 and IL-6). When analyzed separately, IL-8 increased significantly in HI max (p = 0.022) and LO max (p = 0.024); and IL-6 decreased significantly in LO max (p = 0.009) and LO (p = 0.013). No significant overall time effect was observed for sTNFR1 and IL-1RA; however, in HI max sTNFR1 (p = 0.031) and IL-1RA (p = 0.014) increased significantly, but remained unchanged in LO max and LO. IL-1beta, IL-10 and GM-CSF levels remained undetectable in most participants. Nine weeks of resistance training-irrespective of the external load-have beneficial effects on circulating IL-8 and IL-6. In addition, training at high external load increases the anti-inflammatory cytokines sTNFR1 and IL-1RA. The results of this study show that resistance training has anti-inflammatory effects in healthy young persons and that the response of the different inflammatory mediators depends on the magnitude of the external load.

Serum Progranulin Concentrations May Be Associated With Macrophage Infiltration Into Omental Adipose Tissue

PubMed Central

Youn, Byung-Soo; Bang, Sa-Ik; Klöting, Nora; Park, Ji Woo; Lee, Namseok; Oh, Ji-Eun; Pi, Kyung-Bae; Lee, Tae Hee; Ruschke, Karen; Fasshauer, Mathias; Stumvoll, Michael; Blüher, Matthias

2009-01-01

OBJECTIVE—Progranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown. RESEARCH DESIGN AND METHODS—For the measurement of progranulin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating progranulin in a cross-sectional study of 209 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance or type 2 diabetes before and after a 4-week physical training program. Progranulin mRNA and protein expression was measured in paired samples of omental and subcutaneous adipose tissue (adipocytes and cells of the stromal vascular fraction) from 55 lean or obese individuals. Measurement of Erk activation and chemotactic activity induced by progranulin in vitro was performed using THP-1–based cell migration assays. RESULTS—Progranulin serum concentrations were significantly higher in individuals with type 2 diabetes compared with NGT and in obese subjects with predominant visceral fat accumulation. Circulating progranulin significantly correlates with BMI, macrophage infiltration in omental adipose tissue, C-reactive protein (CRP) serum concentrations, A1C values, and total cholesterol. Multivariable linear regression analyses revealed CRP levels as the strongest independent predictor of circulating progranulin. The extent of in vitro progranulin-mediated chemotaxis is similar to that of monocyte chemoattractant protein-1 but independent of Gα. Moreover, in type 2 diabetes, but not in IGT and NGT individuals, physical training for 4 weeks resulted in significantly decreased circulating progranulin levels. CONCLUSIONS—Elevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. We identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that closely reflects omental adipose tissue macrophage infiltration. Physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes. PMID:19056610

Consumption of Honey, Sucrose, and High-Fructose Corn Syrup Produces Similar Metabolic Effects in Glucose-Tolerant and -Intolerant Individuals.

PubMed

Raatz, Susan K; Johnson, LuAnn K; Picklo, Matthew J

2015-10-01

Public health recommendations call for a reduction in added sugars; however, controversy exists over whether all nutritive sweeteners produce similar metabolic effects. The objective was to compare the effects of the chronic consumption of 3 nutritive sweeteners [honey, sucrose, and high-fructose corn syrup containing 55% fructose (HFCS55)] on circulating glucose, insulin, lipids, and inflammatory markers; body weight; and blood pressure in individuals with normal glucose tolerance (GT) and those with impaired glucose tolerance (IGT). In a crossover design, participants consumed daily, in random order, 50 g carbohydrate from assigned sweeteners for 2 wk with a 2- to 4-wk washout period between treatments. Participants included 28 GT and 27 IGT volunteers with a mean age of 38.9 ± 3.6 y and 52.1 ± 2.7 y, respectively, and a body mass index (in kg/m(2)) of 26 ± 0.8 and 31.5 ± 1.0, respectively. Body weight, blood pressure (BP), serum inflammatory markers, lipids, fasting glucose and insulin, and oral-glucose-tolerance tests (OGTTs) were completed pre- and post-treatment. The OGTT incremental areas under the curve (iAUCs) for glucose and insulin were determined and homeostasis model assessment of insulin resistance (HOMA-IR) scores were calculated. Body weight and serum glucose, insulin, inflammatory markers, and total and LDL-cholesterol concentrations were significantly higher in the IGT group than in the GT group at baseline. Glucose, insulin, HOMA-IR, and the OGTT iAUC for glucose or insulin did not differ by treatment, but all responses were significantly higher in the IGT group compared with the GT group. Body weight was unchanged by treatment. Systolic BP was unchanged, whereas diastolic BP was significantly lower in response to sugar intake across all treatments. An increase in high-sensitivity C-reactive protein (hsCRP) was observed in the IGT group in response to all sugars. No treatment effect was observed for interleukin 6. HDL cholesterol did not differ as a result of status or treatment. Triglyceride (TG) concentrations increased significantly from pre- to post-treatment in response to all sugars tested. Daily intake of 50 g carbohydrate from honey, sucrose, or HFCS55 for 14 d resulted in similar effects on measures of glycemia, lipid metabolism, and inflammation. All 3 increased TG concentrations in both GT and IGT individuals and elevated glycemic and inflammatory responses in the latter. This trial was registered at clinicaltrials.gov as NCT01371266. © 2015 American Society for Nutrition.

Inflammatory Markers in the Staging of Bipolar Disorder: A Systematic Review of the Literature.

PubMed

Castaño-Ramírez, Oscar Mauricio; Sepúlveda-Arias, Juan C; Duica, Kelly; Díaz Zuluaga, Ana M; Vargas, Cristian; López-Jaramillo, Carlos

Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder (BD). The evidence suggests that BD may present a progressive course. Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers. The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients. We conducted a systematic review using electronic databases: PubMed, SciELO, LiLACS and PsycINFO. Keywords were divided into inflammatory markers and, BD and staging. Studies involving euthymic BD patients, studies evaluating peripheral biomarkers and studies correlating these with clinical variables related to neuroprogression or stage of BD were included. We present and discuss the methods and findings of ten articles. The inflammatory markers were measured with different techniques and show some contradictories results. The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease. This study suggests that TNF and ILs could play a role in neuroprogression. However, longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression. Copyright © 2017 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Avoidance-related EEG asymmetry predicts circulating interleukin-6.

PubMed

Shields, Grant S; Moons, Wesley G

2016-03-01

Recent research has linked avoidance-oriented motivational states to elevated pro-inflammatory cytokine levels. According to one of many theories regarding the association between avoidance and cytokine levels, because the evolutionarily basic avoidance system may be activated when an organism is threatened or overwhelmed, an associated inflammatory response may be adaptive for dealing with potential injury in such threatening situations. To examine this hypothesis, we tested whether the neural correlate of avoidance motivation associates with baseline levels of the circulating pro-inflammatory cytokine interleukin-6 (IL-6). Controlling for covariates, greater resting neural activity in the right frontal cortex relative to the left frontal cortex-the neural correlate of avoidance motivation-was associated with baseline IL-6. These results thus support the hypothesis that the avoidance motivational system may be closely linked to systemic inflammatory activity. (c) 2016 APA, all rights reserved).

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame.

PubMed

Marotta, Vincenzo; Zatelli, Maria Chiara; Sciammarella, Concetta; Ambrosio, Maria Rosaria; Bondanelli, Marta; Colao, Annamaria; Faggiano, Antongiulio

2018-01-01

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects. © 2018 Society for Endocrinology.

Candidate Markers Associated with the Probability of Future Pulmonary Exacerbations in Cystic Fibrosis Patients

PubMed Central

Wojewodka, Gabriella; De Sanctis, Juan B.; Bernier, Joanie; Bérubé, Julie; Ahlgren, Heather G.; Gruber, Jim; Landry, Jennifer; Lands, Larry C.; Nguyen, Dao; Rousseau, Simon; Benedetti, Andrea; Matouk, Elias; Radzioch, Danuta

2014-01-01

Introduction Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE. Methods We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment. Results Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation. Conclusion Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation. PMID:24533110

Serum fatty acid profile in psoriasis and its comorbidity.

PubMed

Myśliwiec, Hanna; Baran, Anna; Harasim-Symbor, Ewa; Myśliwiec, Piotr; Milewska, Anna Justyna; Chabowski, Adrian; Flisiak, Iwona

2017-07-01

Psoriasis is a chronic inflammatory skin disease that is accompanied by metabolic disturbances and cardio-metabolic disorders. Fatty acids (FAs) might be a link between psoriasis and its comorbidity. The aim of the study was to evaluate serum concentrations of FAs and to investigate their association with the disease activity, markers of inflammation and possible involvement in psoriatic comorbidity: obesity, type 2 diabetes and hypertension. We measured 14 total serum fatty acids content and composition by gas-liquid chromatography and flame-ionization detector after direct in situ transesterification in 85 patients with exacerbated plaque psoriasis and in 32 healthy controls. FAs were grouped according to their biologic properties to saturated FA (SFA), unsaturated FA (UFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA) and n-6 PUFA. Generally, patients characteristic included: Psoriasis Area and Severity Index (PASI), Body Mass Index, inflammatory and biochemical markers, lipid profile and presence of psoriatic comorbidity. We have observed highly abnormal FAs pattern in psoriatic patients both with and without obesity compared to the control group. We have demonstrated association of PASI with low levels of circulating DHA, n-3 PUFA (p = 0.044 and p = 0.048, respectively) and high percent of MUFA (p = 0.024) in the non-obese psoriatic group. The SFA/UFA ratio increased with the duration of the disease (p = 0.03) in all psoriatic patients. These findings indicate abnormal FAs profile in psoriasis which may reflect metabolic disturbances and might play a role in the psoriatic comorbidity.

Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis.

PubMed

Arenillas, Juan F; Alvarez-Sabín, José; Molina, Carlos A; Chacón, Pilar; Fernández-Cadenas, Israel; Ribó, Marc; Delgado, Pilar; Rubiera, Marta; Penalba, Anna; Rovira, Alex; Montaner, Joan

2008-05-01

The molecular pathways involved in the progression of intracranial large artery atherosclerosis (ILA) are largely unknown. Our objective was to prospectively study the relationship between circulating levels of inflammatory markers and fibrinolysis inhibitors, and the risk of progression of symptomatic ILA. Seventy-five consecutive patients with first-ever symptomatic intracranial atherostenosis were studied. Blood levels of C-reactive protein (CRP), E-selectin, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinases 1, 2, 3, 8, 9, 10, and 13, plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were measured 3 months after the qualifying stroke or transient ischemic attack. Thereafter, patients underwent long-term transcranial Doppler follow-up to detect progression of ILA. During a median follow-up time of 23 months, 25 (33%) patients showed ILA progression. Multivariable adjusted Cox regression models and Kaplan-Meier curves showed that high baseline level of CRP, E-selectin, intercellular adhesion molecule-1, matrix metalloproteinase 9, PAI-1, and lipoprotein(a) predicted ILA progression independently of vascular risk factors. Of them, only CRP (CRP>5.5 mg/L; HR, 5.4 [2.3 to 12.7]; P=0.0001) and PAI-1 (PAI-1>23.1 ng/mL; HR, 2.4 [1.0 to 5.8]; P=0.05) predicted ILA progression also independently of the other studied molecules. Progression of symptomatic ILA is associated with a proinflammatory state, as reflected by high levels of inflammatory markers, and with defective fibrinolysis, as indicated by raised concentrations of endogenous fibrinolysis inhibitors.

Engagement with Cognitively-Based Compassion Training is associated with reduced salivary C-reactive protein from before to after training in foster care program adolescents.

PubMed

Pace, Thaddeus W W; Negi, Lobsang Tenzin; Dodson-Lavelle, Brooke; Ozawa-de Silva, Brendan; Reddy, Sheethal D; Cole, Steven P; Danese, Andrea; Craighead, Linda W; Raison, Charles L

2013-02-01

Children exposed to early life adversity (ELA) have been shown to have elevated circulating concentrations of inflammatory markers that persist into adulthood. Increased inflammation in individuals with ELA is believed to drive the elevated risk for medical and psychiatric illness in the same individuals. This study sought to determine whether Cognitively Based Compassion Training (CBCT) reduced C-reactive protein (CRP) in adolescents in foster care with high rates of ELA, and to evaluate the relationship between CBCT engagement and changes in CRP given prior evidence from our group for an effect of practice on inflammatory markers. It was hypothesized that increasing engagement would be associated with reduced CRP from baseline to the 6-week assessment. Seventy-one adolescents in the Georgia foster care system (31 females), aged 13-17, were randomized to either 6 weeks of CBCT or a wait-list condition. State records were used to obtain information about each participant's history of trauma and neglect, as well as reason for placement in foster care. Saliva was collected before and again after 6 weeks of CBCT or the wait-list condition. Participants in the CBCT group completed practice diaries as a means of assessing engagement with the CBCT. No difference between groups was observed in salivary CRP concentrations. Within the CBCT group, practice sessions during the study correlated with reduced CRP from baseline to the 6-week assessment. Engagement with CBCT may positively impact inflammatory measures relevant to health in adolescents at high risk for poor adult functioning as a result of significant ELA, including individuals placed in foster care. Longer term follow-up will be required to evaluate if these changes are maintained and translate into improved health outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased plasma DPP4 activities predict new-onset atherosclerosis in association with its proinflammatory effects in Chinese over a four year period: A prospective study.

PubMed

Zheng, T P; Yang, F; Gao, Y; Baskota, A; Chen, T; Tian, H M; Ran, X W

2014-08-01

DPP4, a novel proinflammatory cytokine, is involved in the inflammatory process through its interaction with IGF-II/M6P receptor. We aimed to investigate whether it could predict new-onset atherosclerosis in Chinese. A prospective study was conducted of 590 adults (213 men and 377 women) aged 18-70 years without atherosclerosis examined in 2007(baseline) and 2011(follow-up). Circulating DPP4 activity, inflammatory markers, IGF-II/M6P receptor and common carotid artery Intima-Media Thickness (C-IMT) were measured at baseline and four years later. At baseline, individuals in the highest quartile of DPP4 activity had higher age, WHR, BMI, SBP, fasting insulin, 2h-PG, TG, LDL-C, IL-6, hs-CRP, IGF-II/M6P-R, C-IMT and lower HDL-C compared with individuals in the lowest quartile. After a 4-year follow-up, 71 individuals developed atherosclerosis. In multiple linear regression analysis, baseline DPP4 activity was an independent predictor of an increase in inflammatory markers, IGF-II/M6P receptor, and C-IMT over a 4-year period (all P < 0.01). In multivariable-adjusted models, the odds ratio (OR) for incident atherosclerosis comparing the highest with the lowest quartiles of DPP4 activity was 3.17 (95%CI 1.33-7.58) after adjustment for confounding risk factors (P = 0.009). The incidence of atherosclerosis owing to DPP4 activity increased by 12.41%. DPP4 activity is an important predictor of the onset of inflammation and atherosclerosis in apparently healthy Chinese. This finding may have important implications for understanding the proinflammatory role of DPP-4 in the pathogenesis of atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A meta-analysis of n-3 polyunsaturated fatty acids effects on circulating acute-phase protein and cytokines in gastric cancer.

PubMed

Mocellin, Michel C; Fernandes, Ricardo; Chagas, Thayz R; Trindade, Erasmo B S M

2018-06-01

Chronic inflammation is related with cancer and leads to worsening prognosis in cancer patients. n-3 polyunsaturated fatty acids (PUFAs) supplementation has been proposed as adjuvant treatment in cancer due anti-inflammatory properties. In the present meta-analysis, we pooled randomized clinical trials (RCTs) assessing the effects of n-3 PUFAs (from fish oil isolated or added in an immunonutrition formula) on inflammatory markers in gastric cancer. A comprehensive literature search was performed in Medline, Scopus, Cochrane library, Science Direct and Web of Science, besides GOOGLE Scholar and a hand searching of reference lists, through July 2016. We pooled the effect size from individual studies using a random-effect model and carried out heterogeneity and sensitivity analyses. Nine trials (698 patients) fulfilled the entry criteria and were included in the synthesis of the systematic review. Eight were carried out in surgical patients and one in patients that received chemotherapy. Four used only fish oil as intervention and five used an immunonutrition formula. Global meta-analysis demonstrated higher albumin (7 studies, SMD 0.28; 95% CI 0.07, 0.48) and prealbumin (4 studies, SMD 0.56; 95% CI 0.12, 1.00) concentrations, and lower IL-6 (2 studies, SMD -0.71; 95% CI -1.15, -0.27) and TNF-α (2 studies, SMD -0.92; 95% CI -1.58, -0.26) concentrations in patients of the intervention group as compared to control group. However, total protein, transferrin and CRP concentrations were not improved by n-3 PUFAs supplementation. This study provides evidence that n-3 PUFAs supplementation from fish oil or added an immunonutrition formula has favorable effects on inflammatory markers in gastric cancer patients undergoing surgical procedures. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Review of commonly used clinical pathology parameters for general gastrointestinal disease with emphasis on small animals.

PubMed

Steiner, Jörg M

2014-01-01

A wide variety of markers are available to assess the function and pathology of the gastrointestinal (GI) tract. This review describes some of these markers with special emphasis given to markers used in dogs and cats. Small intestinal disease can be confirmed and localized by the measurement of serum concentrations of folate and cobalamin. Fecal α1-proteinase inhibitor concentration can increase in individuals with excessive GI protein loss. A wide variety of inflammatory markers are available for a variety of species that can be used to assess the inflammatory activity of various types of inflammatory cells in the GI tract, although most of these markers assess neutrophilic inflammation, such as neutrophil elastase, calprotectin, or S100A12. N-methylhistamine can serve as a marker of mast cell infiltration. Markers for lymphocytic or eosinophilic inflammation are currently under investigation. Exocrine pancreatic function can be assessed by measurement of serum concentrations of pancreatic lipase immunoreactivity (PLI) and trypsin-like immunoreactivity (TLI). Serum PLI concentration is increased in individuals with pancreatitis and has been shown to be highly specific for exocrine pancreatic function and sensitive for pancreatitis. Serum TLI concentration is severely decreased in individuals with exocrine pancreatic insufficiency.

E-Selectin Ligands in the Human Mononuclear Phagocyte System: Implications for Infection, Inflammation, and Immunotherapy.

PubMed

Silva, Mariana; Videira, Paula A; Sackstein, Robert

2017-01-01

The mononuclear phagocyte system comprises a network of circulating monocytes and dendritic cells (DCs), and "histiocytes" (tissue-resident macrophages and DCs) that are derived in part from blood-borne monocytes and DCs. The capacity of circulating monocytes and DCs to function as the body's first-line defense against offending pathogens greatly depends on their ability to egress the bloodstream and infiltrate inflammatory sites. Extravasation involves a sequence of coordinated molecular events and is initiated by E-selectin-mediated deceleration of the circulating leukocytes onto microvascular endothelial cells of the target tissue. E-selectin is inducibly expressed by cytokines (tumor necrosis factor-α and IL-1β) on inflamed endothelium, and binds to sialofucosylated glycan determinants displayed on protein and lipid scaffolds of blood cells. Efficient extravasation of circulating monocytes and DCs to inflamed tissues is crucial in facilitating an effective immune response, but also fuels the immunopathology of several inflammatory disorders. Thus, insights into the structural and functional properties of the E-selectin ligands expressed by different monocyte and DC populations is key to understanding the biology of protective immunity and the pathobiology of several acute and chronic inflammatory diseases. This review will address the role of E-selectin in recruitment of human circulating monocytes and DCs to sites of tissue injury/inflammation, the structural biology of the E-selectin ligands expressed by these cells, and the molecular effectors that shape E-selectin ligand cell-specific display. In addition, therapeutic approaches targeting E-selectin receptor/ligand interactions, which can be used to boost host defense or, conversely, to dampen pathological inflammatory conditions, will also be discussed.

Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis.

PubMed

Ganatra, Hammad A; Varisco, Brian M; Harmon, Kelli; Lahni, Patrick; Opoka, Amy; Wong, Hector R

2017-01-01

Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve survival in a juvenile model of polymicrobial sepsis. Juvenile (13-14-d-old) C57BL/6 mice were treated with 10 mg/kg of zinc via i.p. injections (or vehicle) for 3 d prior to induction of polymicrobial sepsis via i.p. cecal slurry injections. Survival after sepsis was followed for 3 d, and bacterial clearance, ex vivo phagocytosis, systemic inflammatory markers and neutrophil extracellular trap (NET) formation were quantified. We found a significant survival benefit and decreased bacterial burden among zinc supplemented mice when compared with the control group. Zinc supplementation also resulted in enhanced phagocytic activity, greater neutrophil recruitment in the peritoneal cavity and NET formation, suggesting a possible mechanism for improved bacterial clearance and survival. We also noted decreased serum cytokine levels and decreased myeloperoxidase activity in lung tissue following zinc supplementation, suggesting attenuation of the systemic inflammatory response. In conclusion, zinc supplementation improves bacterial clearance, and hence survival, in juvenile mice with polymicrobial sepsis.

Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

PubMed Central

Forney, Laura A.; Lenard, Natalie R.; Stewart, Laura K.

2018-01-01

Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms. PMID:29562620

Reversal of high fat diet-induced obesity through modulating lipid metabolic enzymes and inflammatory markers expressions in rats.

PubMed

A, Kalaivani; Uddandrao, V V Sathibabu; Parim, Brahmanaidu; Ganapathy, Saravanan; P R, Nivedha; Kancharla, Sushma Chandulee; P, Rameshreddy; K, Swapna; Sasikumar, Vadivukkarasi

2018-03-19

In this study, we evaluated the ameliorative potential of Cucurbita maxima seeds oil (CSO (100 mg/kg body weight)) supplementation to high fat diet (HFD)-induced obese rats for 30 days on the changes in body weight, markers of lipid metabolism such as LDL, HDL, triglycerides, total cholesterol, adiponectin, leptin, amylase, and lipase. We also investigated the effects of CSO on the changes of lipid metabolic enzymes such as fatty-acid synthase, acetyl CoA carboxylase, carnitine palmitoyl transferase-1, HMG CoA reductase, and inflammatory markers (TNF-α and IL-6). Administration of CSO revealed significant diminution in body weight gain, altered the activity, expressions of lipid marker enzymes and inflammatory markers. It demonstrated that CSO had considerably altered these parameters when evaluated with HFD control rats. In conclusion, this study suggested that CSO might ameliorate the HFD-induced obesity by altering the enzymes and mRNA expressions important to lipid metabolism.

How to predict clinical relapse in inflammatory bowel disease patients

PubMed Central

Liverani, Elisa; Scaioli, Eleonora; Digby, Richard John; Bellanova, Matteo; Belluzzi, Andrea

2016-01-01

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID:26811644

The effectiveness of Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressIve MultiplE sclerosis patients (RAGTIME): study protocol for a randomized controlled trial.

PubMed

Straudi, Sofia; Manfredini, Fabio; Lamberti, Nicola; Zamboni, Paolo; Bernardi, Francesco; Marchetti, Giovanna; Pinton, Paolo; Bonora, Massimo; Secchiero, Paola; Tisato, Veronica; Volpato, Stefano; Basaglia, Nino

2017-02-27

Gait and mobility impairments affect the quality of life (QoL) of patients with progressive multiple sclerosis (MS). Robot-assisted gait training (RAGT) is an effective rehabilitative treatment but evidence of its superiority compared to other options is lacking. Furthermore, the response to rehabilitation is multidimensional, person-specific and possibly involves functional reorganization processes. The aims of this study are: (1) to test the effectiveness on gait speed, mobility, balance, fatigue and QoL of RAGT compared to conventional therapy (CT) in progressive MS and (2) to explore changes of clinical and circulating biomarkers of neural plasticity. This will be a parallel-group, randomized controlled trial design with the assessor blinded to the group allocation of participants. Ninety-eight (49 per arm) progressive MS patients (EDSS scale 6-7) will be randomly assigned to receive twelve 2-h training sessions over a 4-week period (three sessions/week) of either: (1) RAGT intervention on a robotic-driven gait orthosis (Lokomat, Hocoma, Switzerland). The training parameters (torque of the knee and hip drives, treadmill speed, body weight support) are set during the first session and progressively adjusted during training progression or (2) individual conventional physiotherapy focusing on over-ground walking training performed with the habitual walking device. The same assessors will perform outcome measurements at four time points: baseline (before the first intervention session); intermediate (after six training sessions); end of treatment (after the completion of 12 sessions); and follow-up (after 3 months from the end of the training program). The primary outcome is gait speed, assessed by the Timed 25-Foot Walk Test. We will also assess walking endurance, balance, depression, fatigue and QoL as well as instrumental laboratory markers (muscle metabolism, cerebral venous hemodynamics, cortical activation) and circulating laboratory markers (rare circulating cell populations pro and anti-inflammatory cytokines/chemokines, growth factors, neurotrophic factors, coagulation factors, other plasma proteins suggested by transcriptomic analysis and metabolic parameters). The RAGT training is expected to improve mobility compared to the active control intervention in progressive MS. Unique to this study is the analysis of various potential markers of plasticity in relation with clinical outcomes. ClinicalTrials.gov, identifier: NCT02421731 . Registered on 19 January 2015 (retrospectively registered).

Associated among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

USDA-ARS?s Scientific Manuscript database

Weight loss reduces co-¬morbidities of obesity but decreases bone mass. Our aims were to determine whether adequate dairy intake could prevent weight loss related bone loss and to evaluate the contribution of energy-related hormones and inflammatory markers to bone metabolism. Overweight and obese w...

Lipid profiles, inflammatory markers, and insulin therapy in youth with type 2 diabetes

USDA-ARS?s Scientific Manuscript database

Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poo...

Evaluation of blood neutrophil-lymphocyte ratio and platelet distribution width as inflammatory markers in patients with fibromyalgia.

PubMed

Aktürk, Semra; Büyükavcı, Raikan

2017-08-01

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and systemic symptoms. The aetiology and pathogenesis of fibromyalgia are not yet fully understood. Blood neutrophil/lymphocyte ratio (NLR) is a marker of systemic inflammatory response. Platelet distribution width (PDW) and mean platelet volume (MPV) are the determinants of platelet activation and studied as markers in inflammatory diseases. The aim of the present study was to evaluate levels of NLR,PDW and MPV in patients with fibromyalgia. A total of 197 FMS patients and 53 healthy controls are included in the study. Demographic characteristics, erythrocyte sedimentation rate, C-reactive protein, neutrophil, lymphocyte and platelet counts, platelet distribution width and mean platelet volume levels were recorded. In the patient group, the blood NLR and MPV were significantly higher and the PDW was significantly lower compared to the control group. In the roc curve analysis, blood PDW ≥had 90.4% sensitivity and 90% specificity in predicting fibromyalgia. The results of this study suggest NLR and PDW as promising inflammatory markers indicating fibromyalgia and may be beneficial in facilitating the diagnosis of FMS patients.

Different strains of Propionibacterium acnes modulate differently the cutaneous innate immunity.

PubMed

Jasson, Fiona; Nagy, Istvan; Knol, Anne Chantal; Zuliani, Thomas; Khammari, Amir; Dréno, Brigitte

2013-09-01

Acne is a chronic inflammatory illness of the pilosebaceous follicle where innate immunity plays a central role. In acne, the density of Propionibacterium acnes is increased in the pilosebaceous unit. We hypothesized that the severity of acne is not only dependent on the proliferation of P. acnes but also dependent on the pro-inflammatory potential of P. acnes strains and consequently constitutes potential triggering factor for acne scarring. We investigated pro-inflammatory potential of five different strains of P. acnes and P. avidum in skin explants and the preventive effect of zinc gluconate. The expression of immune markers was studied by immunohistochemistry, RT-qPCR and ELISA. P. acnes strains modulate differently the expression of immune markers both at gene and at protein levels. P. acnes type III had the highest pro-inflammatory potential by up-regulating the expression of PAR-2, TNF-alpha, MMP-13 and TIMP-2, whereas P. avidum had the weakest by up-regulating only MMP-13 and TIMP-2. Preincubation of zinc gluconate, which is a modulator of innate immunity, down-regulates the expression of most immune markers induced by P. acnes, PAR-2, TIMP-2, up-regulates MMP-1, TIMP-1. Our results demonstrate that different P. acnes strains have different inflammatory potential targeting markers of cutaneous innate immunity, and that inflammatory potential can be down-regulated by zinc gluconate. As such, the inflammatory potential of P. acnes strains on acne skin may influence the severity of inflammatory acne lesions and scars. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mind-body interactions in the regulation of airway inflammation in asthma: A PET study of acute and chronic stress

PubMed Central

Rosenkranz, Melissa A.; Esnault, Stephane; Christian, Bradley T.; Crisafi, Gina; Gresham, Lauren K.; Higgins, Andrew T.; Moore, Mollie N.; Moore, Sarah M.; Weng, Helen Y.; Salk, Rachel H.; Busse, William W.; Davidson, Richard J.

2016-01-01

Background Psychological stress has long been recognized as a contributing factor to asthma symptom expression and disease progression. Yet, the neural mechanisms that underlie this relationship have been largely unexplored in research addressing the pathophysiology and management of asthma. Studies that have examined the mechanisms of this relationship in the periphery suggest that it is the superimposition of acute stress on top of chronic stress that is of greatest concern for airway inflammation. Methods We compared asthmatic individuals with high and low levels of chronic life stress in their neural and peripheral physiological responses to the Trier Social Stress Test and a matched control task. We used FDG-PET to measure neural activity during performance of the two tasks. We used both circulating and airway-specific markers of asthma-related inflammation to assess the impact of acute stress in these two groups. Results Asthmatics under chronic stress had a larger HPA-axis response to an acute stressor, which failed to show the suppressive effects on inflammatory markers observed in those with low chronic stress. Moreover, our PET data suggest that greater activity in the anterior insula during acute stress may reflect regulation of the effect of stress on inflammation. In contrast, greater activity in the mid-insula and perigenual anterior cingulate seems to reflect greater reactivity and was associated with greater airway inflammation, a more robust alpha amylase response, and a greater stress-induced increase in proinflammatory cytokine mRNA expression in airway cells. Conclusions Acute stress is associated with increases in markers of airway inflammation in asthmatics under chronic stress. This relationship may be mediated by interactions between the insula and anterior cingulate cortex, that determine the salience of environmental cues, as well as descending regulatory influence of inflammatory pathways in the periphery. PMID:27039241

Mind-body interactions in the regulation of airway inflammation in asthma: A PET study of acute and chronic stress.

PubMed

Rosenkranz, Melissa A; Esnault, Stephane; Christian, Bradley T; Crisafi, Gina; Gresham, Lauren K; Higgins, Andrew T; Moore, Mollie N; Moore, Sarah M; Weng, Helen Y; Salk, Rachel H; Busse, William W; Davidson, Richard J

2016-11-01

Psychological stress has long been recognized as a contributing factor to asthma symptom expression and disease progression. Yet, the neural mechanisms that underlie this relationship have been largely unexplored in research addressing the pathophysiology and management of asthma. Studies that have examined the mechanisms of this relationship in the periphery suggest that it is the superimposition of acute stress on top of chronic stress that is of greatest concern for airway inflammation. We compared asthmatic individuals with high and low levels of chronic life stress in their neural and peripheral physiological responses to the Trier Social Stress Test and a matched control task. We used FDG-PET to measure neural activity during performance of the two tasks. We used both circulating and airway-specific markers of asthma-related inflammation to assess the impact of acute stress in these two groups. Asthmatics under chronic stress had a larger HPA-axis response to an acute stressor, which failed to show the suppressive effects on inflammatory markers observed in those with low chronic stress. Moreover, our PET data suggest that greater activity in the anterior insula during acute stress may reflect regulation of the effect of stress on inflammation. In contrast, greater activity in the mid-insula and perigenual anterior cingulate seems to reflect greater reactivity and was associated with greater airway inflammation, a more robust alpha amylase response, and a greater stress-induced increase in proinflammatory cytokine mRNA expression in airway cells. Acute stress is associated with increases in markers of airway inflammation in asthmatics under chronic stress. This relationship may be mediated by interactions between the insula and anterior cingulate cortex, that determine the salience of environmental cues, as well as descending regulatory influence of inflammatory pathways in the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses.

PubMed

Rubenstein, David A; Hom, Sarah; Ghebrehiwet, Berhane; Yin, Wei

2015-10-01

Kupffer cells are liver resident macrophages that are responsible for screening and clearing blood of pathogens and foreign particles. It has recently been shown that Kupffer cells interact with platelets, through an adhesion based mechanism, to aid in pathogen clearance and then these platelets re-enter the general systemic circulation. Thus, a mechanism has been identified that relates liver inflammation to possible changes in the systemic circulation. However, the role that Kupffer cells play in cardiovascular disease initiation/progression has not been elucidated. Thus, our objective was to determine whether or not Kupffer cells are responsive to a classical cardiovascular risk factor and if these changes can be transmitted into the general systemic circulation. If Kupffer cells initiate inflammatory responses after exposure to classical cardiovascular risk factors, then this provides a potential alternative/synergistic pathway for cardiovascular disease initiation. We aimed to elucidate the prevalence of this potential pathway. We hypothesized that Kupffer cells would initiate a robust inflammatory response after exposure to tobacco cigarette or e-cigarette products and that the inflammatory response would have the potential to antagonize other salient cells for cardiovascular disease progression. To test this, Kupffer cells were incubated with tobacco smoke extracts, e-cigarette vapor extracts or pure nicotine. Complement deposition onto Kupffer cells, Kupffer cell complement receptor expression, oxidative stress production, cytokine release and viability and density were assessed after the exposure. We observed a robust inflammatory response, oxidative stress production and cytokine release after Kupffer cells were exposed to tobacco or e-cigarette extracts. We also observed a marginal decrease in cell viability coupled with a significant decrease in cell density. In general, this was not a function of the extract formulation (e.g. tobacco vs. e-cigarette products or the formulation of the cigarette product). These results indicate that Kupffer cells are responsive to classical cardiovascular risk factors and that an inflammatory response is initiated that may pass into the general systemic circulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The diagnostic value of preoperative inflammatory markers in craniopharyngioma: a multicenter cohort study.

PubMed

Chen, Ming; Zheng, Shi-Hao; Yang, Min; Chen, Zhi-Hua; Li, Shi-Ting

2018-05-01

To compare the different levels of preoperative inflammatory markers in peripheral blood samples between craniopharyngioma (CP) and other sellar region tumors so as to explore their differential diagnostic value. The level of white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, albumin, neutrophil lymphocyte ratio (NLR), derived NLR (dNLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR) and prognostic nutritional index (PNI) were compared between the CP and other sellar region tumors. A receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic significance of the peripheral blood inflammatory markers and their paired combinations for CP including its pathological types. Patients with CP had higher levels of pre-operative WBC, lymphocyte and PNI. The papillary craniopharyngioma (PCP) group had higher neutrophil count and NLR than the adamantinomatous craniopharyngioma (ACP) and healthy control groups whereas the ACP group had higher platelet count and PNI than the PCP and healthy control groups. There were not any significant differences in preoperative inflammatory markers between the primary and recurrent CP groups. The AUC values of WBC, neutrophil, NLR + PLR and dNLR + PLR in PCP were all higher than 0.7. Inflammation seems to be closely correlated with CP's development. The preoperative inflammatory markers including WBC, neutrophil, NLR + PLR and dNLR + PLR may differentially diagnose PCP, pituitary tumor (PT) and Rathke cleft cyst (RCC). In addition, some statistical results in this study indirectly proved previous experimental conclusions and strictly matched CP's biological features.

Acute and Chronic Effects of Endurance Running on Inflammatory Markers: A Systematic Review

PubMed Central

Barros, Edilberto S.; Nascimento, Dahan C.; Prestes, Jonato; Nóbrega, Otávio T.; Córdova, Claúdio; Sousa, Fernando; Boullosa, Daniel A.

2017-01-01

In order to understand the effect of endurance running on inflammation, it is necessary to quantify the extent to which acute and chronic running affects inflammatory mediators. The aim of this study was to summarize the literature on the effects of endurance running on inflammation mediators. Electronic searches were conducted on PubMED and Science Direct with no limits of date and language of publication. Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) investigating the acute and chronic effects of running on inflammation markers in runners were reviewed by two researchers for eligibility. The modified Downs and Black checklist for the assesssments of the methodological quality of studies was subsequently used. Fifty-one studies were finally included. There were no studies with elite athletes. Only two studies were chronic interventions. Results revealed that acute and chronic endurance running may affect anti- and pro-inflammatory markers but methodological differences between studies do not allow comparisons or generalization of the results. The information provided in this systematic review would help practitioners for better designing further studies while providing reference values for a better understanding of inflammatory responses after different running events. Further longitudinal studies are needed to identify the influence of training load parameters on inflammatory markers in runners of different levels and training background. PMID:29089897

CIRCULATING CD11B EXPRESSION CORRELATES WITH THE NEUTROPHIL RESPONSE AND AIRWAY MCD-14 EXPRESSION IS ENHANCED FOLLOWING OZONE EXPOSURE IN HUMANS

EPA Science Inventory

We recently reported that baseline expression of circulating CD11b is associated with the magnitude of the neutrophil response following inhaled endotoxin. In this study, we examined whether circulating CD11b plays a similar role in the inflammatory response following inhaled ozo...

Evidence for circulating cancer stem-like cells and epithelial-mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy.

PubMed

Mirza, Sheefa; Jain, Nayan; Rawal, Rakesh

2017-03-01

Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(-) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.

Vitamin D and inflammatory markers: cross-sectional analyses using data from the English Longitudinal Study of Ageing (ELSA).

PubMed

de Oliveira, Cesar; Biddulph, Jane P; Hirani, Vasant; Schneider, Ione Jayce Ceola

2017-01-01

Recent evidence suggests that low vitamin D concentrations are associated with increased levels of inflammatory markers. However, there are limited studies investigating associations between vitamin D levels and inflammatory markers in the general population and much of this evidence in older adults is inconclusive. Therefore, this study investigates the cross-sectional association of serum 25-hydroxyvitamin D (25(OH)D) levels with inflammatory markers in 5870 older English adults from wave 6 (2012-2013) of the English Longitudinal Study of Ageing (ELSA). ELSA is a large prospective observational study of community-dwelling people aged 50 years and over in England. Serum 25(OH)D levels, C-reactive protein (CRP) levels, plasma fibrinogen levels, white blood cell count (WBC), age, season of blood collection, waist circumference, total non-pension household wealth, measures of health and health behaviours that included depression, number of cardiovascular, non-cardiovascular conditions and difficulties in activities of daily living, smoking, and physical activity were measured. There was a significant negative association between low 25(OH)D levels (≤30 nmol/l) and CRP (OR 1·23, 95 % CI 1·00, 1·51) and WBC (OR 1·35, 95 % CI 1·13, 1·60) that remained after adjustment for a wide range of covariates of clinical significance. However, for fibrinogen, the association did not remain significant when waist circumference was entered in the final model. Our findings showed that 25(OH)D levels were associated with two out the three inflammatory markers investigated. The independent and inverse association between serum 25(OH)D levels and inflammation suggests a potential anti-inflammatory role for vitamin D in older English individuals from the general population.

Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: A sex-stratified analysis in a population-based study.

PubMed

Shafiee, Mojtaba; Tayefi, Maryam; Hassanian, Seyed Mahdi; Ghaneifar, Zahra; Parizadeh, Mohammad Reza; Avan, Amir; Rahmani, Farzad; Khorasanchi, Zahra; Azarpajouh, Mahmoud Reza; Safarian, Hamideh; Moohebati, Mohsen; Heidari-Bakavoli, Alireza; Esmaeili, Habibolah; Nematy, Mohsen; Safarian, Mohammad; Ebrahimi, Mahmoud; Ferns, Gordon A; Mokhber, Naghmeh; Ghayour-Mobarhan, Majid

2017-10-01

Depression and anxiety are two common mood disorders that are both linked to systemic inflammation. Increased white blood cell (WBC) count and red cell distribution width (RDW) are associated with negative clinical outcomes in a wide variety of pathological conditions. WBC is a non-specific inflammatory marker and RDW is also strongly related to other inflammatory markers. Therefore, we proposed that there might be an association between these hematological inflammatory markers and depression/anxiety symptoms. The primary objective of this study was to examine the association between depression/anxiety symptoms and hematological inflammatory markers including WBC and RDW in a large population-based study. Symptoms of depression and anxiety and a complete blood count (CBC) were measured in 9274 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventories. The mean WBC count increased with increasing severity of symptoms of depression and anxiety among men. Male participants with severe depression had significantly higher values of RDW (p<0.001); however, this relationship was less marked among women (p=0.004). In addition, men (but not women) with severe anxiety symptoms had significantly higher values of RDW (p<0.001). Moreover, there was a negative association between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms of depression/anxiety. Our results suggest that higher depression and anxiety scores are associated with an enhanced inflammatory state, as assessed by higher hematological inflammatory markers including WBC and RDW, even after adjusting for potential confounders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unhealthy lifestyle may increase later depression via inflammation in older women but not men.

PubMed

Hiles, Sarah A; Baker, Amanda L; de Malmanche, Theo; McEvoy, Mark; Boyle, Michael; Attia, John

2015-04-01

Depression and inflammatory markers have a reliable cross-sectional association although less is known about the prospective relationship. The current study investigated whether pro-inflammatory markers are prospectively associated with depression, and whether indicators of unhealthy lifestyle, physical health and psychosocial functioning may drive this association. Participants were drawn from the Hunter Community Study, a community-dwelling cohort of individuals aged 55-85 years (N = 1410). Participants completed baseline physiological assessment, health-related questionnaires, and blood sampling for the analysis of inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6. Participants completed the same depressive symptom questionnaire again after 3.5-5.5 years. Depression outcomes at follow-up were analysed dichotomously using established scale cut-off scores and continuously as a "residual score", representing the variation in follow-up depressive symptoms not explained by baseline symptoms and age. Analyses were conducted on males and females separately. At baseline, indicators of unhealthy lifestyle, physical health and psychosocial functioning were associated with depressive symptoms and inflammatory markers. For males, there were no relationships between inflammatory markers and follow-up depression outcomes. In females, IL-6 was significantly associated with depression outcomes in univariate, but not multivariate analyses. However, IL-6 significantly mediated the association between the predictors of waist-to-hip ratio, smoking and psychological coping at baseline, and follow-up depression outcomes. The results support the inflammatory hypothesis of depression, although females may be more vulnerable to effects. The findings raise the possibility that unhealthy lifestyle and psychosocial stress may drive inflammation and subsequent depressive symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pleiotropic genes for metabolic syndrome and inflammation

PubMed Central

Kraja, Aldi T.; Chasman, Daniel I.; North, Kari E.; Reiner, Alexander P.; Yanek, Lisa R.; Kilpeläinen, Tuomas O.; Smith, Jennifer A.; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D.; Feitosa, Mary F.; Tekola-Ayele, Fasil; Chu, Audrey Y.; Nolte, Ilja M.; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A.; Sun, Yan V.; Ritchie, Marylyn D.; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A.; Im, Hae Kyung; Schnabel, Renate B.; Jørgensen, Torben; Jørgensen, Marit E.; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P.; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Ikram, M. Arfan; Richards, J. Brent; Rotimi, Charles; Wilson, James G.; Lange, Leslie; Ganesh, Santhi K.; Nalls, Mike; Rasmussen-Torvik, Laura J.; Pankow, James S.; Coresh, Josef; Tang, Weihong; Kao, W.H. Linda; Boerwinkle, Eric; Morrison, Alanna C.; Ridker, Paul M.; Becker, Diane M.; Rotter, Jerome I.; Kardia, Sharon L.R.; Loos, Ruth J.F.; Larson, Martin G.; Hsu, Yi-Hsiang; Province, Michael A.; Tracy, Russell; Voight, Benjamin F.; Vaidya, Dhananjay; O’Donnell, Christopher; Benjamin, Emelia J.; Alizadeh, Behrooz Z.; Prokopenko, Inga; Meigs, James B.; Borecki, Ingrid B.

2014-01-01

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. PMID:24981077

Pleiotropic genes for metabolic syndrome and inflammation.

PubMed

Kraja, Aldi T; Chasman, Daniel I; North, Kari E; Reiner, Alexander P; Yanek, Lisa R; Kilpeläinen, Tuomas O; Smith, Jennifer A; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D; Feitosa, Mary F; Tekola-Ayele, Fasil; Chu, Audrey Y; Nolte, Ilja M; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A; Sun, Yan V; Ritchie, Marylyn D; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A; Im, Hae Kyung; Schnabel, Renate B; Jørgensen, Torben; Jørgensen, Marit E; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G; Franco, Oscar H; Ikram, M Arfan; Richards, J Brent; Rotimi, Charles; Wilson, James G; Lange, Leslie; Ganesh, Santhi K; Nalls, Mike; Rasmussen-Torvik, Laura J; Pankow, James S; Coresh, Josef; Tang, Weihong; Linda Kao, W H; Boerwinkle, Eric; Morrison, Alanna C; Ridker, Paul M; Becker, Diane M; Rotter, Jerome I; Kardia, Sharon L R; Loos, Ruth J F; Larson, Martin G; Hsu, Yi-Hsiang; Province, Michael A; Tracy, Russell; Voight, Benjamin F; Vaidya, Dhananjay; O'Donnell, Christopher J; Benjamin, Emelia J; Alizadeh, Behrooz Z; Prokopenko, Inga; Meigs, James B; Borecki, Ingrid B

2014-08-01

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

PubMed

Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2017-06-01

The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

Lifecourse social position and D-dimer; findings from the 1958 British birth cohort.

PubMed

Tabassum, Faiza; Kumari, Meena; Rumley, Ann; Power, Chris; Strachan, David P; Lowe, Gordon

2014-01-01

The aim is to examine the association of lifecourse socioeconomic position (SEP) on circulating levels of D-dimer. Data from the 1958 British birth cohort were used, social class was determined at three stages of respondents' life: at birth, at 23 and at 42 years. A cumulative indicator score of SEP (CIS) was calculated ranging from 0 (always in the highest social class) to 9 (always in the lowest social class). In men and women, associations were observed between CIS and D-dimer (P<0.05). Thus, the respondents in more disadvantaged social classes had elevated levels of D-dimer compared to respondents in less disadvantaged social class. In multivariate analyses, the association of disadvantaged social position with D-dimer was largely explained by fibrinogen, C-reactive protein and von Willebrand Factor in women, and additionally by smoking, alcohol consumption and physical activity in men. Socioeconomic circumstances across the lifecourse at various stages also contribute independently to raised levels of D-dimer in middle age in women only. Risk exposure related to SEP accumulates across life and contributes to raised levels of D-dimer. The association of haemostatic markers and social differences in health may be mediated by inflammatory and other markers.

Oxidant Status following Cardiac Surgery with Phosphorylcholine-Coated Extracorporeal Circulation Systems

PubMed Central

Kaya, Ayşem

2016-01-01

Introduction. Extracorporeal circulation (ECC) related systemic oxidative stress is a well-known entity but the underlying mechanisms are not clearly described. Our aim was to investigate the relation between the oxidative stress indices, inflammatory markers, and phosphorylcholine-coated (PCC) ECC systems. Patients and Methods. Thirty-two consecutive coronary artery bypass grafting (CABG) cases were randomly assigned to Group I (PCC, n = 18) and Group II (noncoated, n = 14) ECC circuits. Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), and Procalcitonin (PCT) levels were measured at 5 different time points. The association between the oxidative indices levels and PCC system used was analyzed. Results. In Group I TOS and TAS statuses were increased at T1, T2, T3, and T4, while IL-10 and TNF-α levels accompanied those raises only at T2 (Group I-Group II, 4.73 ± 2.04 versus 2.79 ± 0.63, p = 0.002, and 30.56 ± 8.11 versus 23.97 ± 7.8, p = 0.031, resp.). In contrast, mean TAS and TOS levels were similar to baseline at all time points in Group II but IL-6 and IL-8 levels were increased at T2 (Group I-Group II, 16.84 ± 5.63 versus 44.81 ± 17.0, p = 0.001, and 38.88 ± 9.8 versus 46.14 ± 9.25, p = 0.038, resp.). Conclusion. Even coated ECC systems are still incapable of attenuating the inflammatory response to cardiopulmonary bypass (CPB). PMID:27994711

Hepatocellular Carcinoma is Associated with Gut Microbiota Profile and Inflammation in Non-Alcoholic Fatty Liver Disease.

PubMed

Ponziani, Francesca Romana; Bhoori, Sherrie; Castelli, Chiara; Putignani, Lorenza; Rivoltini, Licia; Del Chierico, Federica; Sanguinetti, Maurizio; Morelli, Daniele; Paroni Sterbini, Francesco; Petito, Valentina; Reddel, Sofia; Calvani, Riccardo; Camisaschi, Chiara; Picca, Anna; Tuccitto, Alessandra; Gasbarrini, Antonio; Pompili, Maurizio; Mazzaferro, Vincenzo

2018-04-17

The gut-liver axis plays a pivotal role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is the third cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study is to explore what features of the gut microbiota are associated with HCC in cirrhotic patients with NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1: 21 patients), NAFLD-related cirrhosis without HCC (group 2: 20 patients) and healthy controls (group 3: 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, whilst intestinal permeability was similar to cirrhotic patients without HCC. Plasma levels of interleukin (IL) 8, IL13, C-C motif chemokine ligand (CCL) 3, CCL4 and CCL5 were higher in the HCC group and were associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of cirrhotic patients showed higher abundance of Enterobacteriaceae and Streptococcus, and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Our results suggest that in cirrhotic patients with NAFLD gut microbiota profile and systemic inflammation are significantly correlated, and can concur in the process of hepatocarcinogenesis. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Oxidant Status following Cardiac Surgery with Phosphorylcholine-Coated Extracorporeal Circulation Systems.

PubMed

Hatemi, Ali Can; Çeviker, Kadir; Tongut, Aybala; Özgöl, İlhan; Mert, Murat; Kaya, Ayşem

2016-01-01

Introduction . Extracorporeal circulation (ECC) related systemic oxidative stress is a well-known entity but the underlying mechanisms are not clearly described. Our aim was to investigate the relation between the oxidative stress indices, inflammatory markers, and phosphorylcholine-coated (PCC) ECC systems. Patients and Methods . Thirty-two consecutive coronary artery bypass grafting (CABG) cases were randomly assigned to Group I (PCC, n = 18) and Group II (noncoated, n = 14) ECC circuits. Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Tumor Necrosis Factor- α (TNF- α ), Interleukin-1 β (IL- β ), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), and Procalcitonin (PCT) levels were measured at 5 different time points. The association between the oxidative indices levels and PCC system used was analyzed. Results . In Group I TOS and TAS statuses were increased at T 1, T 2, T 3, and T 4, while IL-10 and TNF- α levels accompanied those raises only at T 2 (Group I-Group II, 4.73 ± 2.04 versus 2.79 ± 0.63, p = 0.002, and 30.56 ± 8.11 versus 23.97 ± 7.8, p = 0.031, resp.). In contrast, mean TAS and TOS levels were similar to baseline at all time points in Group II but IL-6 and IL-8 levels were increased at T 2 (Group I-Group II, 16.84 ± 5.63 versus 44.81 ± 17.0, p = 0.001, and 38.88 ± 9.8 versus 46.14 ± 9.25, p = 0.038, resp.). Conclusion . Even coated ECC systems are still incapable of attenuating the inflammatory response to cardiopulmonary bypass (CPB).

The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

PubMed

Kim, Minjoo; Kim, Minkyung; Han, Ji Yun; Lee, Sang-Hyun; Jee, Sun Ha; Lee, Jong Ho

2017-03-01

To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A 2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A 2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A 2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

Inflammatory response and extracorporeal circulation.

PubMed

Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander

2015-06-01

Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Associations among body composition, inflammatory profile and disease extent in ulcerative colitis patients.

PubMed

Urbano, Ana Paula Signori; Sassaki, Ligia Yukie; Dorna, Mariana de Souza; Presti, Paula Torres; Carvalhaes, Maria Antonieta de Barros Leite; Martini, Ligia Araújo; Ferreira, Ana Lucia Anjos

2018-02-01

The aim of our study was to assess body composition status and its association with inflammatory profile and extent of intestinal damage in ulcerative colitis patients during clinical remission. This is a cross-sectional study in which body composition data (phase angle [PhA], fat mass [FM], triceps skin fold thickness [TSFt], mid-arm circumference [MAC], mid-arm muscle circumference [MAMC], adductor pollicis muscle thickness [APMt]), inflammatory profile (C-reactive protein [CRP], a1-acid glycoprotein, erythrocyte sedimentation rate [ESR]) and disease extent were recorded. The mean age of the 59 patients was 48.1 years; 53.3% were women. Most patients were in clinical remission (94.9%) and 3.4% was malnourished according to body mass index. PhA was inversely correlated with inflammatory markers such as CRP (R=-0.59; p<0.001) and ESR (R=-0.46; p<0.001) and directly correlated with lean mass: MAMC (R=0.31; p=0.01) and APMt (R=0.47; p<0.001). Lean mass was inversely correlated with non-specific inflammation marker (APMt vs. ESR) and directly correlated with hemoglobin values (MAMC vs. hemoglobin). Logistic regression analysis revealed that body cell mass was associated with disease extent (OR 0.92; 95CI 0.87-0.97; p<0.01). PhA was inversely correlated with inflammatory markers and directly correlated with lean mass. Acute inflammatory markers were correlated with disease extent. Body cell mass was associated with disease extent.

[The degree of chronic renal failure is associated with the rate of pro-inflammatory cytokines, hyperhomocysteinemia and with oxidative stress].

PubMed

Tbahriti, H F; Messaoudi, A; Kaddous, A; Bouchenak, M; Mekki, K

2014-06-01

To evaluate pro-inflammatory cytokines, homocysteinemia and markers of oxidative status in the course of chronic renal failure. One hundred and two patients (male/female: 38/64; age: 45±07 years) with chronic renal failure were divided into 4 groups according to the National Kidney Foundation classification. They included 28 primary stage renal failure patients, 28 moderate stage renal failure, 28 severe stage renal failure and 18 end stage renal failure. The inflammatory status was evaluated by the determination of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) and total homocysteine. Pro-oxidant status was assessed by assaying thiobarbituric acid reactive substances, hydroperoxides, and protein carbonyls. Antioxidant defence was performed by analysis of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase. Inflammatory markers were elevated in the end stage renal failure group compared to the other groups (P<0.001). Indeed, an increase in thiobarbituric acid reactive substances, hydroperoxides and protein carbonyls was noted in the end stage renal failure group in comparison with the other groups (P<0.001), while the levels of antioxidants enzymes activity were decreased in the study population (P<0.001). Impaired renal function is closely associated with the elevation of inflammatory markers leading to both increased markers of oxidative stress and decreased antioxidant defense. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Circulating follicular helper T cells in Crohn's disease (CD) and CD-associated colorectal cancer.

PubMed

Wang, Zhenlong; Wang, Zhiming; Diao, Yanqing; Qian, Xiaoli; Zhu, Nan; Dong, Wen

2014-09-01

Follicular helper T cells (Tfh) represent a distinct subset of CD4+ T cells specialized in providing help to B lymphocytes. Studies have indicated that Tfh in circulating blood can act as a prognostic marker for diseases. In the current study, we investigated the percentages of circulating Tfh (CTfh) in Crohn's disease (CD) and CD-associated colorectal cancer (CRC). CTfh and it subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 using flow cytometry in 32 healthy controls and 78 CD patients, which included 16 CD-associated CRC. Data showed that proportion of CTfh in CD4+ T cells was significantly increased in CD patients (9.8 %) than in controls (5.1 %) (p < 0.01). Further analysis revealed that the upregulation of CTfh was contributed by CTfh-Th1 subtype and CTfh-Th17 subtype. Investigating the behavior of the patients demonstrated that prevalence of CTfh was significantly elevated in penetrating CD (20.9 %) than inflammatory CD (8.2 %) or stricturing CD (7.5 %). In addition, we analyzed CTfh in CD-associated CRC, and identified that patients with CRC had 1.59-fold higher percentage of CTfh than patients without CRC (p < 0.01). Furthermore, the distribution of CTfh subsets was significantly altered in patients with the cancer. This study suggests the involvement of CTfh in CD and CD-associated CRC, in which the effect of CTfh is partially different between these two diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Hong Seo; Lee, Hyun Min; Kim, Won-Tae

Highlights: • This study generates a monoclonal antibody CA27 against the mycoplasmal p37 protein. • CA27 isolates circulating tumor cells (CTCs) from the blood of liver cancer patients. • Results show the first evidence for mycoplasma infected-CTCs in cancer patients. - Abstract: Many studies have shown that persistent infections of bacteria promote carcinogenesis and metastasis. Infectious agents and their products can modulate cancer progression through the induction of host inflammatory and immune responses. The presence of circulating tumor cells (CTCs) is considered as an important indicator in the metastatic cascade. We unintentionally produced a monoclonal antibody (MAb) CA27 against themore » mycoplasmal p37 protein in mycoplasma-infected cancer cells during the searching process of novel surface markers of CTCs. Mycoplasma-infected cells were enriched by CA27-conjugated magnetic beads in the peripheral blood mononuclear cells in patients with hepatocellular carcinoma (HCC) and analyzed by confocal microscopy with anti-CD45 and CA27 antibodies. CD45-negative and CA27-positive cells were readily detected in three out of seven patients (range 12–30/8.5 ml blood), indicating that they are mycoplasma-infected circulating epithelial cells. CA27-positive cells had larger size than CD45-positive hematological lineage cells, high nuclear to cytoplasmic ratios and irregular nuclear morphology, which identified them as CTCs. The results show for the first time the existence of mycoplasma-infected CTCs in patients with HCC and suggest a possible correlation between mycoplasma infection and the development of cancer metastasis.« less

Potential Anti-Inflammatory Treatment of Ischemic Heart Disease

PubMed Central

Hodzic, Enisa

2018-01-01

Introduction Ischemic heart disease (IHD) is clinical manifestation of chronic inflammatory progressive pathological process of atherosclerosis in coronary arteries. IHD is the leading cause of morbidity and mortality in the world. The question is whether it is possible to improve and direct the therapeutic treatment of IHD patients in the treatment of the inflammatory process in the atherosclerotic leasions. Material and Methods A prospective, comparative, analytica,clinically applicable, open-type study was performed. The study was conducted on 80 subjects with controlled biohumoral markers: troponin, CK, CK MB, BNP; markers of atherogenesis: LDL and homocystein; inflammatory markers: CRP, amyloid, cytokines IL-2, IL-6,TNF-alpha. The experimental group of 38 respondents had in addition to the conventional IHD treatment with: ampicillin (which included organosulfur compounds), cyancobalamin, vitamin B complex (B1, B2 and B6) and folacin. A control group of 42 respondents did not have this additional treatment. Results Major adverse cardic events (MACE) such as postinfarctic angina pectoris and repeated infarction, need for surgical interventions of myocardial revascularization, signs of cardiac insufficiency and death were observed during the one-year period. There was no correlation between the IL-2, IL-6 and TNF-alpha, as well as CK, CKMB and troponin and MACE in one-year follow-up. There was a strong positive correlation between MACE and CRP (p = 0,0002) and amyloid (p = 0,0005) as inflamatory markers; a strong positive correlation between MACE and homocysteine as an atherogenic marker (p = 0,0002, and amoderate positive correlation between MACE and BNP (p = 0.0403) as ischemic marker and marker of cardiac insufficiency. The echocardiographically monitored systolic function showed a moderate difference in the groups with average higher values in the experimantal group (p = 0.0282). Conclusion The applied treatment exhibited a moderate positive effect on the systolic function of LV and significantly reduced the MACE in the work compared to the control group (p <0.0001), and demonstrated a potential anti-inflammatory effect. PMID:29736096

Early Life Adversity Is Associated With Elevated Levels of Circulating Leptin, Irisin, and Decreased Levels of Adiponectin in Midlife Adults

PubMed Central

Joung, Kyoung Eun; Park, Kyung-Hee; Zaichenko, Lesya; Sahin-Efe, Ayse; Thakkar, Bindiya; Brinkoetter, Mary; Usher, Nicole; Warner, Dorothy; Davis, Cynthia R.; Crowell, Judith A.

2014-01-01

Context: Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known. Objectives: The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP). Design/Subjects/Setting: This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP. Results: Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity. Conclusion: Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity. PMID:24650014

Mucosal integrity and inflammatory markers in the female lower genital tract as potential screening tools for vaginal microbicides.

PubMed

Su, H Irene; Schreiber, Courtney A; Fay, Courtney; Parry, Sam; Elovitz, Michal A; Zhang, Jian; Shaunik, Alka; Barnhart, Kurt

2011-11-01

In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety. A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI). Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1β (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel. Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study. Copyright © 2011 Elsevier Inc. All rights reserved.

The inflammatory response after out-of-hospital cardiac arrest is not modified by targeted temperature management at 33 °C or 36 °C.

PubMed

Bro-Jeppesen, John; Kjaergaard, Jesper; Wanscher, Michael; Nielsen, Niklas; Friberg, Hans; Bjerre, Mette; Hassager, Christian

2014-11-01

Survivors after cardiac arrest (CA) exhibits a systemic inflammatory response as part of post-cardiac arrest syndrome (PCAS). We investigated the association between systemic inflammation and severity of PCAS and whether level of targeted temperature management (TTM) modifies level of the inflammatory response. We studied 169 patients included at a single center in the TTM-trial, randomly assigned to TTM at 33 °C or 36 °C for 24 h. Plasma samples were analyzed for inflammatory markers including interleukin (IL) IL-1β,IL-4,IL-6,IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and procalcitonin (PCT) at randomization and 24, 48 and 72 h after CA. Severity of PCAS was assessed by Sequential Organ Failure Assessment (SOFA) score. Plasma levels of both IL-6 and IL-10 determined at randomization correlated with severity of PCAS at day 2 (r=0.36 and r=0.27, p<0.001) and day 3 (r=0.32 and r=0.22, p<0.001). IL-6 at randomization was an independent predictor of severity of PCAS at day 2 (p=0.003) and day 3 (p<0.0001) and was a significantly stronger predictor of severity of PCAS at day 3 compared to CRP (p=0.04) and PCT (p=0.03). Level of TTM did not modify level of the inflammatory markers IL-1β, IL-6, TNF-α, IL-4, IL-10, CRP and PCT, (p=NS for each inflammatory marker). Level of inflammatory response was associated with severity of PCAS with IL-6 being consistently and more strongly associated with severity of PCAS than the inflammatory markers CRP and PCT. The systemic inflammatory response after CA was not modified by TTM at 33 °C or 36 °C. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Serological markers in inflammatory bowel disease: the pros and cons.

PubMed

Lerner, Aaron; Shoenfeld, Yehuda

2002-02-01

Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease. Among several serological markers anti-Saccharomyces cerevisiae mannan antibodies and perinuclear antineutrophil cytoplasmic autoantibodies are highly disease specific for Crohn's disease and ulcerative colitis, respectively. Combining the two improves their specificity. Sensitivity, however, is still low. Due to lack of standardization and vast interobserver variability, they cannot be used as the only diagnostic criteria but can assist clinicians in diagnosing and categorizing patients with inflammatory bowel disease as well as in helping them to take therapeutic decisions.

Regulation of diet-induced adipose tissue and systemic inflammation by salicylates and pioglitazone.

PubMed

Kim, Myung-Sunny; Yamamoto, Yasuhiko; Kim, Kyungjin; Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E; Lee, Jongsoon

2013-01-01

It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6C(hi)), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that anti-diabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes.

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs.

PubMed

Abu-Farha, Mohamed; Behbehani, Kazem; Elkum, Naser

2014-04-09

Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47-6.19) and (OR = 2.52, 95% CI = 1.45-4.35), (OR = 4.26, 95% CI = 2.39-7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12-0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs.

Unfavorable inflammatory profile in adults at risk of type 2 diabetes identified by hemoglobin A1c levels according to the American Diabetes Association criteria.

PubMed

Fiorentino, T V; Hribal, M L; Perticone, M; Andreozzi, F; Sciacqua, A; Perticone, F; Sesti, G

2015-04-01

We aimed to evaluate the inflammatory profile of individuals with prediabetes defined by HbA1c levels, according to the new American Diabetes Association criteria, and to determine the ability of HbA1c to identify individuals with subclinical inflammation independently of the contribution of other metabolic parameters such as fasting, 1- or 2-h post-load glucose (PG) levels. High sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen, white blood cells (WBC) count and complement C3 (C3) were assessed, and oral glucose tolerance test (OGTT) was performed in 711 adults. Subjects were stratified into three groups according to their HbA1c levels. Poor agreement existed between HbA1c and 2-h PG criteria for identification of individuals with prediabetes (κ coefficient = 0.300). As compared with subjects having HbA1c <5.7 % (39 mmol/mol), individuals with prediabetes (HbA1c 5.7-6.4 %, [39-46 mmol/mol]) exhibited a significant increase of the concentration of five inflammatory markers (hsCRP, ESR, fibrinogen, WBC count, C3) as well as of a cluster of inflammatory markers, as measured by an inflammatory score after adjusting for sex, age, smoking, fasting, 1- and 2-h PG levels. In multiple regression models including sex, age, body mass index, smoking habit, fasting, 1- and 2-h PG levels, and HOMA index, HbA1c levels were significant independent contributors to each of the five inflammatory markers examined. These data suggest that HbA1c is a reliable marker of glucose homeostasis, and may identify individuals at increased risk of diabetes with unfavorable inflammatory profile independently from fasting and 2-h PG levels.

Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates.

PubMed

Sursal, Tolga; Stearns-Kurosawa, Deborah J; Itagaki, Kiyoshi; Oh, Sun-Young; Sun, Shiqin; Kurosawa, Shinichiro; Hauser, Carl J

2013-01-01

Systemic inflammatory response syndrome (SIRS) is a fundamental host response common to bacterial infection and sterile tissue injury. Systemic inflammatory response syndrome can cause organ dysfunction and death, but its mechanisms are incompletely understood. Moreover, SIRS can progress to organ failure or death despite being sterile or after control of the inciting infection. Biomarkers discriminating between sepsis, sterile SIRS, and postinfective SIRS would therefore help direct care. Circulating mitochondrial DNA (mtDNA) is a damage-associated molecular pattern reflecting cellular injury. Circulating bacterial 16S DNA (bDNA) is a pathogen-associated pattern (PAMP) reflecting ongoing infection. We developed quantitative polymerase chain reaction assays to quantify these markers, and predicting their plasma levels might help distinguish sterile injury from infection. To study these events in primates, we assayed banked serum from Papio baboons that had undergone a brief challenge of intravenous Bacillus anthracis delta Sterne (modified to remove toxins) followed by antibiotics (anthrax) that causes organ failure and death. To investigate the progression of sepsis to "severe" sepsis and death, we studied animals where anthrax was pretreated with drotrecogin alfa (activated protein C), which attenuates sepsis in baboons. We also contrasted lethal anthrax bacteremia against nonlethal E. coli bacteremia and against sterile tissue injury from Shiga-like toxin 1. Bacterial DNA and mtDNA levels in timed samples were correlated with blood culture results and assays of organ function. Sterile injury by Shiga-like toxin 1 increased mtDNA, but bDNA was undetectable: consistent with the absence of infection. The bacterial challenges caused parallel early bDNA and mtDNA increases, but bDNA detected pathogens even after bacteria were undetectable by culture. Sublethal E. coli challenge only caused transient rises in mtDNA consistent with a self-limited injury. In lethal anthrax challenge (n = 4), bDNA increased transiently, but mtDNA levels remained elevated until death, consistent with persistent septic tissue damage after bacterial clearance. Critically, activated protein C pretreatment (n = 4) allowed mtDNA levels to decay after bacterial clearance with sparing of organ function and survival. In summary, host tissue injury correlates with mtDNA whether infective or sterile. Mitochondrial DNA and bDNA polymerase chain reactions can quantify tissue injury incurred by septic or sterile mechanisms and suggest the source of SIRS of unknown origin.

Gene expression markers of age-related inflammation in two human cohorts.

PubMed

Pilling, Luke C; Joehanes, Roby; Melzer, David; Harries, Lorna W; Henley, William; Dupuis, Josée; Lin, Honghuang; Mitchell, Marcus; Hernandez, Dena; Ying, Sai-Xia; Lunetta, Kathryn L; Benjamin, Emelia J; Singleton, Andrew; Levy, Daniel; Munson, Peter; Murabito, Joanne M; Ferrucci, Luigi

2015-10-01

Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40-92 yrs) and InCHIANTI study (n=694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n=194, 35.6% mediated, p=0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation. Published by Elsevier Inc.

Characterization of Microparticles after Hepatic Ischemia-Reperfusion Injury

PubMed Central

Freeman, Christopher M.; Quillin, Ralph C.; Wilson, Gregory C.; Nojima, Hiroyuki; Johnson, Bobby L.; Sutton, Jeffrey M.; Schuster, Rebecca M.; Blanchard, John; Edwards, Michael J.; Caldwell, Charles C.; Lentsch, Alex B.

2014-01-01

Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver. PMID:24879335

Inflammatory Markers and Breast Cancer Risk

DTIC Science & Technology

2010-07-01

cancer [26, 27] or cytologic atypia [28], while another observed elevated IL-6 levels among breast cancer cases with insulin resistance [29]. Five...1 AD_________________ AWARD NUMBER: W81XWH-06-1-0533 TITLE: Inflammatory markers and breast ...and breast cancer risk 5a. CONTRACT NUMBER W81XWH-06-1-0533 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Brenda

Pyostomatitis vegetans. Clinical marker of ulcerative colitis.

PubMed

Lopez-Jornet, P; Gomez-Garcia, F; Camacho-Alonso, F

2012-03-01

Pyodermatitis-pyostomatitis vegetans (PV), a rare disorder of the skin and oral mucosa, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. We have presented the case of a patient with PV. This report emphasizes the relationship of PV to inflammatory bowel disease and the importance of the oral lesions as initial presenting signs of systemic disease or activity.

EFFECT OF THREE DIFFERENT SIZED FRACTIONS OF OUTDOOR PM ON INFLAMMATORY AND OXIDATIVE MARKERS IN VIVO

EPA Science Inventory

EFFECT OF THREE DIFFERENT SIZED FRACTIONS OF OUTDOOR PM ON INFLAMMATORY MARKERS IN VIVO
C A J Dick', P Singh2, P. Evansky3, S Becker3 and M I Gilmour3.
'Center For Environmental Medicine and Lung Biology, UNC, Chapel Hill, NC 27599 2NCSU, Raleigh, NC 'Experimental Toxicolog...

Peripheral inflammatory markers in amnestic mild cognitive impairment.

PubMed

Karim, Salman; Hopkins, Steve; Purandare, Nitin; Crowther, Jackie; Morris, Julie; Tyrrell, Pippa; Burns, Alistair

2014-03-01

To prospectively monitor plasma inflammatory marker concentrations in peripheral blood, over 12 months, in subjects with amnestic mild cognitive impairment (MCI), and to determine the relationship between peripheral inflammatory markers and cognitive decline. Seventy patients with amnestic MCI were recruited from two sites providing specialist memory assessment services in Manchester. The baseline assessment included physical examination, neuro-psychological testing and venous blood samples for C-reactive protein (CRP) and interleukin 6 (IL-6) concentrations. Sixty two participants were followed up after 12 months and the assessments were repeated. Data analysis revealed a significant rise in CRP, but not IL-6 concentrations over 12 months, which was not confounded by demographic variables. The neuro-psychological test scores had no association with CRP or IL-6 concentrations at baseline or 12 months follow-up. This study adopted the unique approach of prospectively investigating peripheral inflammatory markers in a cohort with amnestic MCI. A significant rise in CRP concentrations over 12 months, but lack of significant association with cognition, provide no evidence for a relationship between systemic inflammation and cognitive decline in amnestic MCI. © 2013 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.

Inflammatory reactions in placental blood of Plasmodium falciparum-infected women and high concentrations of soluble E-selectin and a circulating P. falciparum protein in the cord sera.

PubMed Central

Jakobsen, P H; Rasheed, F N; Bulmer, J N; Theisen, M; Ridley, R G; Greenwood, B M

1998-01-01

To better understand reasons for increased susceptibility to malaria in pregnancy; and the interrelationships between maternal malaria, local immune reactions and the development of the fetus, concentrations of soluble interleukin-10 (IL-10), cytokine receptors, adhesion molecules, a Plasmodium falciparum protein, glutamate-rich protein (GLURP) and antibodies to P. falciparum rhoptry-associated protein-1 were measured among 105 Gambian women and their neonates. Peripheral blood concentrations of IL-10, soluble cytokine receptors and soluble adhesion molecules were found to be different from those concentrations measured in the placenta. Markers of inflammatory reactions: IL-10, sIL-2R, sIL-4R, and soluble tumour necrosis factor receptor I (sTNF-RI) were found in high concentrations in the placenta, indicating that inflammatory reactions take place in the placenta which has been regarded as an immunoprivileged site. Concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intracellular adhesion molecule-1 (sICAM-1), potential adhesion receptors for malaria parasites, were associated with an active P. falciparum infection in the placenta although the associations did not reach significance. P. falciparum exoantigen, GLURP, was detected in cord blood indicating transplacental passage of malarial antigens. Concentrations of E-selectin were higher in cord blood samples compared with peripheral blood samples. This appeared to be associated with development of cord endothelial cells and not with P. falciparum infection. PMID:9616377

Inflammatory Cytokines as Uremic Toxins: "Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son".

PubMed

Castillo-Rodríguez, Esmeralda; Pizarro-Sánchez, Soledad; Sanz, Ana B; Ramos, Adrian M; Sanchez-Niño, Maria Dolores; Martin-Cleary, Catalina; Fernandez-Fernandez, Beatriz; Ortiz, Alberto

2017-03-23

Chronic kidney disease is among the fastest growing causes of death worldwide. An increased risk of all-cause and cardiovascular death is thought to depend on the accumulation of uremic toxins when glomerular filtration rate falls. In addition, the circulating levels of several markers of inflammation predict mortality in patients with chronic kidney disease. Indeed, a number of cytokines are listed in databases of uremic toxins and uremic retention solutes. They include inflammatory cytokines (IL-1β, IL-18, IL-6, TNFα), chemokines (IL-8), and adipokines (adiponectin, leptin and resistin), as well as anti-inflammatory cytokines (IL-10). We now critically review the cytokines that may be considered uremic toxins. We discuss the rationale to consider them uremic toxins (mechanisms underlying the increased serum levels and evidence supporting their contribution to CKD manifestations), identify gaps in knowledge, discuss potential therapeutic implications to be tested in clinical trials in order to make this knowledge useful for the practicing physician, and identify additional cytokines, cytokine receptors and chemokines that may fulfill the criteria to be considered uremic toxins, such as sIL-6R, sTNFR1, sTNFR2, IL-2, CXCL12, CX3CL1 and others. In addition, we suggest that IL-10, leptin, adiponectin and resistin should not be considered uremic toxins toxins based on insufficient or contradictory evidence of an association with adverse outcomes in humans or preclinical data not consistent with a causal association.

Update on the pathogenesis of Scleroderma: focus on circulating progenitor cells.

PubMed

Brunasso, Alexandra Maria Giovanna; Massone, Cesare

2016-01-01

In systemic sclerosis (SSc), the development of fibrosis seems to be a consequence of the initial ischemic process related to an endothelial injury. The initial trigger event in SSc is still unknown, but circulating progenitor cells (CPCs) might play a key role. Such cells have the ability to traffic into injury sites, exhibiting inflammatory features of macrophages, tissue remodeling properties of fibroblasts, and vasculogenesis functions of endothelial cells. The different subsets of CPCs described thus far in SSc arise from a pool of circulating monocyte precursors (CD14 (+) cells) and probably correspond to a different degree of differentiation of a single cell of origin. Several subsets of CPCs have been described in patients with SSc, all have a monocytic origin but may or may not express CD14, and all of these cells have the ability to give origin to endothelial cells, or collagen (Col)-producing cells, or both. We were able to identify six subsets of CPCs: pluripotent stem cells (CD14 (+), CD45 (+), and CD34 (+)), monocyte-derived multipotential cells (MOMCs) or monocyte-derived mesenchymal progenitors (CD14 (+), CD45 (+), CD34 (+), Col I (+), CD11b (+), CD68 (+), CD105 (+), and VEGFR1 (+)), early endothelial progenitor cells (EPCs) or monocytic pro-angiogenic hematopoietic cells or circulating hematopoietic cells (CD14 (+), CD45 (+), CD34 (low/-), VEGFR2 (+/-), CXCR4 (+), c-kit (+), and DC117 (+)), late EPCs (CD14 (-), CD133 (+), VEGFR2 (+), CD144 (+) [VE-cadherin (+)], and CD146 (+)), fibroblast-like cells (FLCs)/circulating Col-producing monocytes (CD14 (+), CD45 (+), CD34 (+/-), and Col I (+)), and fibrocytes (CD14 (-), CD45 (+), CD34 (+), Col I (+), and CXCR4 (+)). It has been demonstrated that circulating CD14 (+) monocytes with an activated phenotype are increased in patients with SSc when compared with normal subjects. CD14 (+), CD34 (+), and Col I (+) spindle-shaped cells have been found in increased numbers in lungs of SSc patients with interstitial lung disease. Elevated blood amounts of early EPCs have been found in patients with SSc by different groups of researchers and such levels correlate directly with the interstitial lung involvement. The prevalence of hematopoietic markers expressed by CPCs that migrate from blood into injury sites in SSc differs and changes according to the degree of differentiation. CXCR4 is the most commonly expressed marker, followed by CD34 and CD45 at an end stage of differentiation. Such difference also indicates a continuous process of cell differentiation that might relate to the SSc clinical phenotype (degree of fibrosis and vascular involvement). A deeper understanding of the role of each subtype of CPCs in the development of the disease will help us to better classify patients in order to offer them targeted approaches in the future.

Clinical evaluation of multiple inflammation biomarkers for diagnosis and prognosis for patients with systemic inflammatory response syndrome.

PubMed

Reichsoellner, M; Raggam, R B; Wagner, J; Krause, R; Hoenigl, M

2014-11-01

A multiplexed biomarker bundle consisting of nine different inflammation markers was evaluated regarding their diagnostic and prognostic performances in 159 adult systemic inflammatory response syndrome (SIRS) patients enrolled at the emergency department. Fibronectin, interleukin-8 (IL-8), biotin, and neutrophil gelatinase-associated lipocalin (NGAL) were the most robust markers but were not superior to the already established markers IL-6, C-reactive protein (CRP), procalcitonin (PCT), and soluble urokinase plasminogen activator receptor (suPAR). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

HOX Genes as Potential Markers of Circulating Tumour Cells.

PubMed

Morgan, R; El-Tanani, M

2016-01-01

Circulating tumour cells (CTCs) have significant diagnostic potential as they can reflect both the presence and recurrence of a wide range of cancers. However, this potential continues to be limited by the lack of robust and accessible isolation technologies. An alternative to isolation might be their direct detection amongst other peripheral blood cells, although this would require markers that allow them to be distinguished from an exceptionally high background signal. This review assesses the potential role of HOX genes, a family of homeodomain containing transcription factors with key roles in both embryonic development and oncogenesis, as unique and possibly disease specific markers of CTCs.

Sleep and inflammatory markers in different psychiatric disorders.

PubMed

Krysta, Krzysztof; Krzystanek, Marek; Bratek, Agnieszka; Krupka-Matuszczyk, Irena

2017-02-01

Many psychiatric disorders, like schizophrenia, affective disorders, addictions and different forms of dementia are associated with sleep disturbances. In the etiology and course of those diseases inflammatory processes are regarded to be an increasingly important factor. They are also a frequently discussed element of the pathology of sleep. In this literature review reports on correlations between poor sleep and inflammatory responses in various psychiatric conditions are discussed. The link between schizophrenia, affective disorders and inflammatory cytokines is a complex phenomenon, which has been already confirmed in a number of studies. However, the presence of sleep deficits in those conditions, being a common symptom of depression and psychoses, can be an additional factor having a considerable impact on the immunological processes in mental illnesses. In the analyzed data, a number of studies are presented describing the role of inflammatory markers in sleep disturbances and psychopathological symptoms of affective, psychotic, neurogenerative and other disorders. Also attention is drawn to possible implications for their treatment. Efforts to use, e.g., anti-inflammatory agents in psychiatry in the context of their impact on sleep are reported. The aspect of inflammatory markers in the role of sleep deprivation as the treatment method in major depressive disorder is also discussed. A general conclusion is drawn that the improvement of sleep quality plays a crucial role in the care for psychiatric patients.

Circulating RNAs as new biomarkers for detecting pancreatic cancer

PubMed Central

Kishikawa, Takahiro; Otsuka, Motoyuki; Ohno, Motoko; Yoshikawa, Takeshi; Takata, Akemi; Koike, Kazuhiko

2015-01-01

Pancreatic cancer remains difficult to treat and has a high mortality rate. It is difficult to diagnose early, mainly due to the lack of screening imaging modalities and specific biomarkers. Consequently, it is important to develop biomarkers that enable the detection of early stage tumors. Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses. These circulating RNAs are upregulated in the serum and plasma of cancer patients, including those with pancreatic cancer, compared with healthy controls. The majority of RNA biomarker studies have assessed circulating microRNAs (miRs), which are often tissue-specific. There are few reports of the tumor-specific upregulation of other types of small non-coding RNAs (ncRNAs), such as small nucleolar RNAs and Piwi-interacting RNAs. Long ncRNAs (lncRNAs), such as HOTAIR and MALAT1, in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers. Among tissue-derived RNAs, some miRs show increased expression even in pre-cancerous tissues, and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma. Additionally, some miRs and lncRNAs have been reported with significant alterations in expression according to disease progression, and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established. Furthermore, recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers. Although much work is required to clarify the release mechanism, origin of tumor-specific circulating RNAs, and selectivity of carrier complexes, and technical advances must also be achieved, such as creating a consensus normalization protocol for quantitative data analysis, circulating RNAs are largely unexplored and might represent novel clinical biomarkers. PMID:26229396

Bidirectional Prospective Associations Between Cardiac Autonomic Activity and Inflammatory Markers.

PubMed

Hu, Mandy Xian; Lamers, Femke; Neijts, Melanie; Willemsen, Gonneke; de Geus, Eco J C; Penninx, Brenda W J H

2018-06-01

Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers. Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6. The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = -.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up. Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.

Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden?

PubMed

Gotsman, Israel; Stabholz, Ayala; Planer, David; Pugatsch, Thea; Lapidus, Ludmila; Novikov, Yelena; Masrawa, Siham; Soskolne, Aubrey; Lotan, Chaim

2008-07-01

Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease. To determine the relationship between inflammatory markers and the angiographic severity of CAD. We measured inflammatory markers in consecutive patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay. There was a significant correlation between TNFalpha and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFalpha; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P< 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFalpha (P< 0.05) and combined levels of TNFalpha and IL-6 (P< 0.05). IL-6 levels were independently predictive of Gensini coronary score (P< 0.05). TNFalpha and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Association between matrix metalloproteinase-10 concentration and smoking in individuals without cardiovascular disease.

PubMed

Páramo, José A; Beloqui, Oscar; Rodríguez, José A; Diez, Javier; Orbe, Josune

2008-12-01

Smoking is an important cardiovascular risk factor whose underlying mechanism is incompletely understood. However, it has been suggested that alterations in the balance between synthesis and degradation of the extracellular matrix (ECM) may play a role. The aim of this study was to determine whether there is an independent association between smoking and the concentration of circulating metalloproteinases (MMPs) in individuals without cardiovascular disease. Metabolic parameters, the carotid intima-media thickness (IMT), inflammatory markers (fibrinogen, C-reactive protein and interleukin-6), markers of endothelial damage (e.g., von Willebrand factor), and the concentration of MMP-1, -9 and -10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in 400 asymptomatic individuals with cardiovascular risk factors. Subjects were divided into non-smokers (n=195), smokers (n=118) and former smokers (n=87). In addition, global cardiovascular risk was determined from PROCAM and REGICOR scores. Both MMP-1 and MMP-10 concentrations were significantly higher in smokers than non-smokers (P< .05 and P< .001, respectively), though there was no difference in the levels of MMP-9, TIMP-1, IMT and other inflammatory parameters. There were positive correlations between the MMP-10 concentration and PROCAM and REGICOR scores (P< .001). Multivariate analysis showed that there was still an association between smoking and the MMP-10 concentration after adjustment for age, sex and other cardiovascular risk factors (P< .001). Multiple regression analysis showed that smoking accounted for 28% of the variability in the MMP-10 concentration. There was an independent association between smoking and the MMP-10 concentration in asymptomatic individuals. This relationship between MMP-10 and the ECM may indicate a mechanism through which this MMP contributes to smoking-related atherosclerosis.

Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

PubMed Central

Canelles, Sandra; Argente, Jesús; Barrios, Vicente

2016-01-01

ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model.

PubMed

Baquedano, Eva; Burgos-Ramos, Emma; Canelles, Sandra; González-Rodríguez, Agueda; Chowen, Julie A; Argente, Jesús; Barrios, Vicente; Valverde, Angela M; Frago, Laura M

2016-05-01

Insulin receptor substrate-2-deficient (IRS2(-/-)) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2(-/-) mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2(-/-) mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2(-/-) mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2(-/-) mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. © 2016. Published by The Company of Biologists Ltd.

Lifestyle and metabolic approaches to maximizing erectile and vascular health.

PubMed

Meldrum, D R; Gambone, J C; Morris, M A; Esposito, K; Giugliano, D; Ignarro, L J

2012-01-01

Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.

In vivo microvascular and macrovascular endothelial function is not associated with circulating dimethylarginines in patients with rheumatoid arthritis: a prospective analysis of the DRACCO cohort.

PubMed

Dimitroulas, Theodoros; Sandoo, Aamer; Hodson, James; Smith, Jacqueline P; Kitas, George D

2016-07-01

To examine associations between asymmetric (ADMA), symmetric dimethylarginine (SDMA) and ADMA:SDMA ratio with assessments of endothelial function and coronary artery perfusion in RA patients. ADMA and SDMA levels were measured in 197 RA individuals [144 (77.4%) females, median age: 66 years (quartiles: 59-73)]. Patients underwent assessments of microvascular endothelium-dependent and endothelium-independent function, macrovascular endothelium-dependent and endothelium-independent function and vascular morphology (pulse wave analysis, carotid intima-media thickness (cIMT), and carotid plaque). Coronary perfusion was assessed by subendocardial viability ratio (SEVR). SEVR correlated with SDMA (r = 0.172, p = 0.026) and ADMA:SDMA (r = -0.160, p = 0.041) in univariable analysis, but not in multivariable analysis accounting for confounding factors. Neither ADMA:SDMA ratio nor SDMA were significantly correlated with microvascular or macrovascular endothelial function, or with arterial stiffness and cIMT. Within subgroup of patients (n = 26) with high inflammatory markers, a post-hoc analysis showed that SDMA and the ADMA:SDMA ratio were significantly associated with endothelium-dependent microvascular function in univariable analysis, with Pearson's r correlation coefficients of -0.440 (p = 0.031) and 0.511 (p = 0.011), respectively. Similar finding were established between ADMA:SDMA ratio and arterial stiffness in univariable analysis, with Pearson's r of 0.493, (p = 0.024). Dimethylarginines were not found to be significantly associated with several assessments of vascular function and morphology in patients with RA, however, post-hoc analysis indicates that there may be associations in patients with raised inflammatory markers. Our results suggest that dysregulated NO metabolism may not be the sole mechanism for the development of preclinical atherosclerosis in RA.

Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors β1 and β2

PubMed Central

Echeverría, César; Montorfano, Ignacio; Tapia, Pablo; Riedel, Claudia; Cabello-Verrugio, Claudio

2014-01-01

During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endothelial cells (ECs), inducing dysfunction of the ECs. We previously reported that endotoxins induce the conversion of ECs into activated fibroblasts. Through endotoxin-induced endothelial fibrosis, ECs change their morphology and their protein expression pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic inducers are transforming growth factor β1 (TGF-β1) and TGF-β2. However, whether TGF-β1 and TGF-β2 participate in endotoxin-induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF-β receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus suggesting that endotoxin elicits TGF-β production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF-β1 and TGF-β2. Endotoxin-treated ECs induced the expression and secretion of TGF-β1 and TGF-β2. TGF-β1 and TGF-β2 downregulation inhibited the endotoxin-induced changes in the endothelial marker VE-cadherin and in the fibrotic proteins α-SMA and fibronectin. Thus, endotoxin induces the production of TGF-β1 and TGF-β2 as a mechanism to promote endotoxin-induced endothelial fibrosis. To the best of our knowledge, this is the first report showing that endotoxin induces endothelial fibrosis via TGF-β secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotoxin-induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseases. PMID:24935972

Endotoxin-induced endothelial fibrosis is dependent on expression of transforming growth factors β1 and β2.

PubMed

Echeverría, César; Montorfano, Ignacio; Tapia, Pablo; Riedel, Claudia; Cabello-Verrugio, Claudio; Simon, Felipe

2014-09-01

During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endothelial cells (ECs), inducing dysfunction of the ECs. We previously reported that endotoxins induce the conversion of ECs into activated fibroblasts. Through endotoxin-induced endothelial fibrosis, ECs change their morphology and their protein expression pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic inducers are transforming growth factor β1 (TGF-β1) and TGF-β2. However, whether TGF-β1 and TGF-β2 participate in endotoxin-induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF-β receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus suggesting that endotoxin elicits TGF-β production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF-β1 and TGF-β2. Endotoxin-treated ECs induced the expression and secretion of TGF-β1 and TGF-β2. TGF-β1 and TGF-β2 downregulation inhibited the endotoxin-induced changes in the endothelial marker VE-cadherin and in the fibrotic proteins α-SMA and fibronectin. Thus, endotoxin induces the production of TGF-β1 and TGF-β2 as a mechanism to promote endotoxin-induced endothelial fibrosis. To the best of our knowledge, this is the first report showing that endotoxin induces endothelial fibrosis via TGF-β secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotoxin-induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseases. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Endotoxin-induced lung alveolar cell injury causes brain cell damage.

PubMed

Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia R M; Pelosi, Paolo; Villar, Jesús

2015-01-01

Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. © 2014 by the Society for Experimental Biology and Medicine.

An in vitro test system for compounds that modulate human inflammatory macrophage polarization.

PubMed

Shiratori, Hiromi; Feinweber, Carmen; Luckhardt, Sonja; Wallner, Nadja; Geisslinger, Gerd; Weigert, Andreas; Parnham, Michael J

2018-06-16

Macrophages undergo activation by pathophysiological stimuli to pro-inflammatory and bactericidal, or wound-healing and anti-inflammatory phenotypes, termed M1 or M2, respectively. Dysregulation of the M1-M2 balance is often associated with inflammatory diseases. Therefore, mechanisms of macrophage polarization may reveal new drug targets. We profiled six compounds with claimed modulatory effects on macrophage polarization using peripheral blood monocyte-derived macrophages. Based on the distinct mRNA or protein expression in macrophages stimulated either with M1 [lipopolysaccharide (LPS) + interferon-γ, IFNγ] or M2 interleukin-4 (IL-4) stimuli, we selected a combination of M1 (IL1β, tumor necrosis factor-α,TNFα, CC chemokine receptor 7, CCR7 and CD80) and M2 (chemokine (C-C motif) ligand 22, CCL22, CD200R and mannose receptor C type 1, MRC1) markers to monitor drug effects on "M1 polarization" or cells "pre-polarized to M1". Azithromycin (25-50μM), tofacitinib (2.5-5μM), hydroxychloroquine (40µg/ml) and pioglitazone (15-60μM) exhibit an anti-inflammatory profile because they downregulated M1 markers and upregulated some M2 markers when given both before and after M1 polarization. Lovastatin given before M1 polarization downregulated M1 marker genes but enhanced the M1 phenotype in macrophages pre-polarized with LPS and IFNγ. Methotrexate (1.25-5μM) did not modulate macrophage polarization. We have, thus, established a test system suitable to identify novel compounds or repurposed drugs that modulate inflammatory macrophage plasticity. Compounds with potential to reduce expression of molecules involved in inflammatory T cell activation (IL-1β, TNFα, CD80), while enhancing production of a major chemokine involved in recruitment of Tregs (CCL22) may be of interest for treating chronic inflammatory diseases. Copyright © 2018. Published by Elsevier B.V.

Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations

PubMed Central

Mobarrez, Fariborz; Vikerfors, Anna; Gustafsson, Johanna T.; Gunnarsson, Iva; Zickert, Agneta; Larsson, Anders; Pisetsky, David S.; Wallén, Håkan; Svenungsson, Elisabet

2016-01-01

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS+/PS−), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2–10 times more abundant in SLE blood compared to controls. PS− MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS− MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS− MPs, suggests a generalized disturbance in SLE. MPs may be regarded as “liquid biopsies” to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis. PMID:27777414

Plasma ANGPTL-4 is Associated with Obesity and Glucose Tolerance: Cross-Sectional and Longitudinal Findings.

PubMed

Barja-Fernandez, Silvia; Moreno-Navarrete, José María; Folgueira, Cintia; Xifra, Gemma; Sabater, Mònica; Castelao, Cecilia; FernØ, Johan; Leis, Rosaura; Diéguez, Carlos; Casanueva, Felipe F; Ricart, Wifredo; Seoane, Luisa M; Fernandez-Real, José Manuel; Nogueiras, Rubén

2018-05-01

Angiopoietin-like protein 4 (ANGPTL-4) regulates plasma lipoprotein levels, but its relevance in human obesity and type 2 diabetes (T2D) is largely unknown. We aim to investigate the regulation of circulating ANGPTL-4 levels in obesity, T2D, and after changes in body weight. Circulating ANGPTL-4 levels were measured in two different cohorts. First, in a cross-sectional study, we evaluated ANGPTL-4 levels in lean and obese patients with normoglycemia or with altered glucose tolerance (AGT; n = 282). Second, in a longitudinal intervention study, 51 obese participants were evaluated. A hypocaloric diet was prescribed, with follow-up 2 years later. ANGPTL-4 levels were significantly increased in obese patients with AGT compared to lean participants. Moreover, ANGPTL-4 was positively correlated with BMI, waist circumference, fat mass, HbA1c, HOMA-IR, fasting triglycerides, and with inflammatory markers. Participants gaining weight after the follow-up showed increased ANGPTL-4 levels in parallel to increased BMI, fat mass, and fasting glucose, while ANGPTL-4 levels were reduced in participants losing weight. Our data support a relevant role of ANGPTL-4 in human obesity and its involvement in long-term body weight changes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of irradiation on release of endothelial microparticles (EMP) in vitro.

PubMed

Neuber, Christin; Pufe, Johanna; Pietzsch, Jens

2015-01-01

Survivors of Hodgkin's disease as well as of breast and lung cancer are at risk of radiation-associated cardiovascular disease. Recent studies demonstrated a correlation between cardiovascular risk factors and circulating endothelial microparticles (EMP) and thereby suggest increased EMP levels in circulation to be an early biomarker of endothelial dysfunction and cardiovascular risk. This prompted us to analyze the amount of EMP released by human aortic endothelial cells (HAEC) after exposure to different doses of X-ray (0.4, 2, 4, 6, and 20 Gy) using antibodies against the endothelial cell markers CD31, CD144, and CD146 by flow cytometry. In this pilot experiment only CD146 proved appropriate for quantification of HAEC-derived EMP. Exposure of HAEC to different doses of X-ray did not significantly influence formation of CD146-positive EMP. However, low doses (0.4 Gy) tended to decrease EMP formation, whereas higher doses (2 or 4 Gy) slightly increased release of CD146-positive EMP. By contrast, inflammatory activation of HAEC by TPA significantly increased EMP release about 15-fold (P <  0.01). In conclusion, under the present experimental conditions EMP did not prove a suitable biomarker for radiation-induced endothelial dysfunction in vitro.

Do Circulating Tumor Cells, Exosomes, and Circulating Tumor Nucleic Acids Have Clinical Utility?

PubMed Central

Gold, Bert; Cankovic, Milena; Furtado, Larissa V.; Meier, Frederick; Gocke, Christopher D.

2016-01-01

Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided. PMID:25908243

The Role of Inflammasome in Inflammatory Macrophage in Mycobacterium Avium Complex-lung Disease and Mycobacterium Abscessus-lung Disease

ClinicalTrials.gov

2014-06-27

To Investigate the Inflammasome Response of Inflammatory and Resting Macrophage; To Compare the Difference of Inflammasome Response of Inflammatory Macrophage; To Study the Diagnostic Aid From Immunological Markers in Inflammasome Response

The Impact of Physical Activity on Serum Inflammatory Markers in Overweight Pubertal Boys: 24-Month Follow-Up Study.

PubMed

Remmel, Liina; Tillmann, Vallo; Mengel, Eva; Kool, Pille; Purge, Priit; Lätt, Evelin; Jürimäe, Jaak

2018-05-01

To investigate the differences in the pattern of changes in serum inflammatory cytokines measured annually over a 24-month period, between less active and more active overweight boys. In total, 25 pubertal overweight boys were divided by their moderate to vigorous physical activity (MVPA) levels into 2 groups: less active group (LAG; n = 10; MVPA < 60 min/d) and more active group (MAG; n = 15; MVPA > 60 min/d). Physical activity was measured by 7-day accelerometry. Serum concentration of 13 inflammatory cytokines [interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, vascular endothelial growth factor, interferon-γ, tumor necrosis factor-α, monocyte chemotactic protein-1, epidermal growth factor, and C-reactive protein] was measured at baseline (T0), after 12 months (T1), and after 24 months (T2) from fasting blood samples. Serum IL-6 level was significantly higher [LAG: 1.27 (0.86, 1.98) pg/mL; MAG: 0.80 (0.52, 0.84) pg/mL] at T0 and IL-8 level [LAG: 10.26 (8.80, 11.64) pg/mL; MAG: 7.42 (6.10, 9.54) pg/mL] at T2 in LAG compared with MAG. The changes over the study period varied between different inflammatory markers. None of the slopes of any measured markers were statistically different between the LAG and MAG, although the slopes of interferon-γ and IL-10 tended to be different between the groups. The pattern of changes over the study period varied between different inflammatory markers, but these changes were not different between the MVPA groups. More longitudinal studies are needed to investigate whether IL-6, IL-8, IL-10, and interferon-γ would be the choice of inflammatory markers to study the associations between obesity and physical activity in future.

C-reactive protein and other markers of inflammation in hemodialysis patients

PubMed Central

Heidari, Behzad

2013-01-01

Hemodialysis patients are at greater risk of cardiovascular disease. Higher than expected cardiovascular morbidity and mortality in this population has been attributed to dislipidemia as well as inflammation. The causes of inflammation in hemodialysis patients are multifactorial. Several markers were used for the detection of inflammatory reaction in patients with chronic renal disease. These markers can be used for the prediction of future cardiovascular events. Among the several parameters of inflammatory markers, serum, CRP is well known and its advantages for the detection of inflammation and its predictor ability has been evaluated in several studies. This review addressed the associated factors and markers of inflammation in hemodialysis patients. In addition, their ability in predicting future atherosclerosis and effect of treatment has been reviewed. However, this context particularly in using CRP as a prediction marker of inflammation and morbidity requires further studies. PMID:24009946

C-reactive protein and other markers of inflammation in hemodialysis patients.

PubMed

Heidari, Behzad

2013-01-01

Hemodialysis patients are at greater risk of cardiovascular disease. Higher than expected cardiovascular morbidity and mortality in this population has been attributed to dislipidemia as well as inflammation. The causes of inflammation in hemodialysis patients are multifactorial. Several markers were used for the detection of inflammatory reaction in patients with chronic renal disease. These markers can be used for the prediction of future cardiovascular events. Among the several parameters of inflammatory markers, serum, CRP is well known and its advantages for the detection of inflammation and its predictor ability has been evaluated in several studies. This review addressed the associated factors and markers of inflammation in hemodialysis patients. In addition, their ability in predicting future atherosclerosis and effect of treatment has been reviewed. However, this context particularly in using CRP as a prediction marker of inflammation and morbidity requires further studies.

Acute phase protein haptoglobin as inflammatory marker in serum and synovial fluid in an equine model of arthritis.

PubMed

Barrachina, Laura; Remacha, Ana Rosa; Soler, Lourdes; García, Natalia; Romero, Antonio; Vázquez, Francisco José; Vitoria, Arantza; Álava, María Ángeles; Lamprave, Fermín; Rodellar, Clementina

2016-12-01

Acute phase proteins are useful inflammatory markers in horses. Haptoglobin (Hp) serum level is increased in horses undergoing different inflammatory processes, including arthritis. However, Hp concentration has not been assessed in inflammatory synovial fluid (SF). The aim of the present study was to investigate the Hp response in serum and SF in horses undergoing experimentally induced arthritis. For this purpose, serum and SF samples were collected from 12 animals before amphotericin B-induced arthritis was created (T0, healthy) and 15days after the lesion induction (T1, joint inflammation) and Hp was determined by single radial immunodiffusion. The Hp increase between T0 and T1 was significant in both serum and SF, and serum Hp concentration at T0 was significantly higher than in SF, but significant differences were not found at T1, indicating a higher Hp increase in SF. A significant positive correlation for Hp concentration between serum and SF samples was found. These results highlight the potential usefulness of Hp as inflammatory marker in horses, showing for the first time the increase of Hp in SF from joint inflammation in the horse. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolomic characterization of laborers exposed to welding fumes.

PubMed

Wang, Kuo-Ching; Kuo, Ching-Hua; Tian, Tze-Feng; Tsai, Mong-Hsun; Chiung, Yin-Mei; Hsiech, Chun-Ming; Tsai, Sung-Jeng; Wang, San-Yuan; Tsai, Dong-Ming; Huang, Chiang-Ching; Tseng, Y Jane

2012-03-19

The complex composition of welding fumes, multiplicity of molecular targets, diverse cellular effects, and lifestyles associated with laborers vastly complicate the assessment of welding fume exposure. The urinary metabolomic profiles of 35 male welders and 16 male office workers at a Taiwanese shipyard were characterized via (1)H NMR spectroscopy and pattern recognition methods. Blood samples for the same 51 individuals were also collected, and the expression levels of the cytokines and other inflammatory markers were examined. This study dichotomized the welding exposure variable into high (welders) versus low (office workers) exposures to examine the differences of continuous outcome markers-metabolites and inflammatory markers-between the two groups. Fume particle assessments showed that welders were exposed to different concentrations of chromium, nickel, and manganese particles. Multivariate statistical analysis of urinary metabolomic patterns showed higher levels of glycine, taurine, betaine/TMAO, serine, S-sulfocysteine, hippurate, gluconate, creatinine, and acetone and lower levels of creatine among welders, while only TNF-α was significantly associated with welding fume exposure among all cytokines and other inflammatory markers measured. Of the identified metabolites, the higher levels of glycine, taurine, and betaine among welders were suspected to play some roles in modulating inflammatory and oxidative tissue injury processes. In this metabolomics experiment, we also discovered that the association of the identified metabolites with welding exposure was confounded by smoking, but not with drinking, which is a finding consistent with known modified response of inflammatory markers among smokers. Our results correspond with prior studies that utilized nonmetabolomic analytical techniques and suggest that the metabolomic profiling is an efficient method to characterize the overall effect of welding fume exposure and other confounders. © 2012 American Chemical Society

Common Genetic Contributions to Depressive Symptoms and Inflammatory Markers in Middle-Aged Men: The Twins Heart Study

PubMed Central

Su, Shaoyong; Miller, Andrew H.; Snieder, Harold; Bremner, J. Douglas; Ritchie, James; Maisano, Carisa; Jones, Linda; Murrah, Nancy V.; Goldberg, Jack; Vaccarino, Viola

2010-01-01

Objective To examine the extent to which a common genetic pathway is also involved in the relationship between depressive symptoms, in the absence of major depressive disorder (MDD), and inflammation. Recent data suggested that MDD and inflammation share common genes. Methods We recruited 188 male twins from the Vietnam Era Twin Registry who were free of symptomatic coronary artery disease and MDD, with mean ± standard deviation (SD) age of 55 ± 2.75 years, including 54 monozygotic and 40 dizygotic twin pairs. These pairs were assessed for two inflammatory markers, interleukin (IL)-6 and C-reactive protein (CRP). Current depressive symptoms were measured with the Beck Depression Inventory-II. Generalized estimating equations were used to examine the phenotypic association between depression and inflammatory markers. Biometrical genetic modeling was performed to estimate the genetic and environmental contributions to this association. Results An association was observed between severity of current depressive symptoms and increased levels of inflammatory markers (p < .001 for IL-6 and p = .005 for CRP). After adjustment for other factors, the association was slightly attenuated but remained statistically significant for IL-6 (p = .002). The heritability of IL-6, CRP, and depressive symptoms were estimated as 0.37, 0.65, and 0.48, respectively. Genetic modeling found a significant genetic correlation between IL-6 and depressive symptoms (rG = 0.22, p = .046), indicating that about 66% of the covariance between them can be explained by shared genetic influences. Conclusions Current depressive symptoms are significantly correlated with inflammatory markers. This covariation is due, in large part, to genes that are common to depressive symptoms and inflammation. PMID:19073752

An in vitro evaluation of the anti-inflammatory effects of platelet-rich plasma, ketorolac, and methylprednisolone.

PubMed

Mazzocca, Augustus D; McCarthy, Mary Beth R; Intravia, Jessica; Beitzel, Knut; Apostolakos, John; Cote, Mark P; Bradley, James; Arciero, Robert A

2013-04-01

The purpose of this study was to quantify the extent of the anti-inflammatory effect of platelet-rich plasma (PRP) in a controlled in vitro environment. Through the stimulation of human umbilical vein endothelial cells with inflammatory cytokines (tumor necrosis factor α and interferon γ), cell adhesion molecule expression (E-selectin, vascular cell adhesion molecule, and human leukocyte antigen DR) and PRP's anti-inflammatory effect can be measured. PRP was produced from 3 individuals using a single-spin (PRPLP) process. Treatment groups include negative (unstimulated) controls, positive (stimulated) controls, ketorolac tromethamine, methylprednisolone, PRP, ketorolac-PRP, and methylprednisolone-PRP. A fluorescence assay of the cellular inflammation markers was measured by the BioTek Synergy HT plate reader (BioTek Instruments, Winooski, VT) at 0, 1, 2, and 5 days. At days 2 and 5, methylprednisolone treatment showed a 2.1- to 5.8-fold reduction (P < .05) in inflammation markers over PRP. In addition, PRP and ketorolac showed a 1.4- to 2.5-fold reduction (P < .05) in cellular inflammation markers over the control. There was no statistically significant difference between ketorolac and PRP. Although PRP and ketorolac reduced cellular inflammation markers (E-selectin, vascular cell adhesion molecule, and human leukocyte antigen DR) compared with control, neither caused as great a reduction as methylprednisolone. Although PRP and ketorolac did not produce as significant a reduction in cellular inflammation markers as methylprednisolone, they reduced cellular inflammation compared with the control. These agents may have clinical application as injectable anti-inflammatory medications. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine.

PubMed

Della Corte, Vittoriano; Tuttolomondo, Antonino; Pecoraro, Rosaria; Di Raimondo, Domenico; Vassallo, Valerio; Pinto, Antonio

2016-01-01

In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage renal disease and in elderly populations. The endothelium has emerged as the key regulator of vascular homeostasis, in fact, it has not merely a barrier function but also acts as an active signal transducer for circulating influences that modify the vessel wall phenotype. When its function is lost, it predisposes the vasculature to vasoconstriction, leukocyte adherence, platelet activation, thrombosis and atherosclerosis. Non-invasive methods were developed to evaluate endothelial function, such as the assesment of FMD, L-FMC and RHI. Moreover in the last years, a large number of studies have clarified the role of inflammation and the underlying cellular and molecular mechanisms that contribute to atherogenesis. For clinical purposes, the most promising inflammatory biomarker appears to be CRP and a variety of population-based studies have showed that baseline CRP levels predict future cardiovascular events. Each of the markers listed above has its importance from the pathophysiological and clinical point of view, and those can also be good therapeutic targets. However, it must be stressed that assessments of these vascular markers are not mutually exclusive, but rather complementary and those can offer different views of the same pathology. The purpose of this review is to analyze the role of arterial stiffness, endothelial dysfunction and immunoinflammatory markers as surrogate endpoint, assessing the correlations between these markers and evaluating the therapeutic perspectives that these offer.

Serum from Diesel Exhaust-Exposed Rats with Cardiac Dysfunction Alters Aortic Endothelial Cell Function In Vitro: Circulating Mediators as Causative Factors?

EPA Science Inventory

Although circulating inflammatory mediators are strongly associated with adverse cardiovascular outcomes triggered by inhaled air pollution, direct cause-effect linkage has not been established. Given that endothelial toxicity often precedes and precipitates cardiac dysfunction, ...

Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial.

PubMed

Vors, Cécile; Couillard, Charles; Paradis, Marie-Eve; Gigleux, Iris; Marin, Johanne; Vohl, Marie-Claude; Couture, Patrick; Lamarche, Benoît

2018-03-01

High-fat meals induce postprandial inflammation. Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action. There is also an increasing body of evidence supporting the role of curcumin, a polyphenol from the curcuminoid family, as a modulator of proinflammatory processes. The objectives of this study were to investigate the following: 1) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal; and 2) the acute combined effects of this combination on the postprandial inflammatory response of subjects with abdominal obesity. In a double blind, crossover, randomized, placebo-controlled study, 11 men and 11 postmenopausal women [mean ± SD age: 62 ± 5 y; mean ± SD body mass index (in kg/m2): 29 ± 3] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1-2 wk: once after consumption of a dietary supplement (200 mg resveratrol and 100 mg curcumin, Res/Cur) and once after consumption of a placebo (cellulose). Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers, adhesion molecules, and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests. Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations. Supplementation with Res/Cur did not modify postprandial variations in circulating inflammatory markers (C-reactive protein, IL-6, IL-8, monocyte chemoattractant protein-1) and adhesion molecules [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1] compared to placebo (PTreatment×Time > 0.05). However, Res/Cur significantly decreased the cumulative postprandial response of sVCAM-1, compared to placebo (incremental area under the curve -4643%, P = 0.01). Postprandial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments. Acute supplementation with Res/Cur has no impact on the postprandial inflammation response to a high-fat meal in abdominally obese older adults. Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal. This trial was registered at clinicaltrials.gov as NCT01964846.

Lymphocytes and macrophages in adipose tissue in obesity: markers or makers of subclinical inflammation?

PubMed

Cinkajzlová, Anna; Mráz, Miloš; Haluzík, Martin

2017-05-01

Obesity is accompanied by the development of chronic low-grade inflammation in adipose tissue. The presence of chronic inflammatory response along with metabolically harmful factors released by adipose tissue into the circulation is associated with several metabolic complications of obesity such as type 2 diabetes mellitus or accelerated atherosclerosis. The present review is focused on macrophages and lymphocytes and their possible role in low-grade inflammation in fat. Both macrophages and lymphocytes respond to obesity-induced adipocyte hypertrophy by their migration into adipose tissue. After activation and differentiation, they contribute to the development of local inflammatory response and modulation of endocrine function of adipose tissue. Despite intensive research, the exact role of lymphocytes and macrophages within adipose tissue is only partially clarified and various data obtained by different approaches bring ambiguous information with respect to their polarization and cytokine production. Compared to immunocompetent cells, the role of adipocytes in the obesity-related adipose tissue inflammation is often underestimated despite their abundant production of factors with immunomodulatory actions such as cytokines or adipokines such as leptin, adiponektin, and others. In summary, conflicting evidence together with only partial correlation of in vitro findings with true in vivo situation due to great heterogeneity and molecular complexity of tissue environment calls for intensive research in this rapidly evolving and important area.

Circulating Bone Marrow-Derived CD45-/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn's Disease.

PubMed

Boltin, Doron; Kamenetsky, Zvi; Perets, Tsachi Tsadok; Snir, Yifat; Sapoznikov, Boris; Schmilovitz-Weiss, Hemda; Ablin, Jacob Nadav; Dickman, Ram; Niv, Yaron

2017-03-01

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn's disease (CD) have yielded conflicting results. To determine whether the circulating levels of EPCs are changed in the context of CD. CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers. Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = -0.13, p = 0.47), CDAI (r = -0.26, p = 0.15), disease duration (r = -0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99). EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.

Circulating microRNAs as potential biomarkers of aerobic exercise capacity.

PubMed

Mooren, Frank C; Viereck, Janika; Krüger, Karsten; Thum, Thomas

2014-02-15

Purpose microRNAs (miRs) are crucial intracellular mediators of various biological processes, also affecting the cardiovascular system. Recently, it has been shown that miRs circulate extracellularly in the bloodstream and that such circulating miRs change in response to physical activity. Therefore, the purpose of the current study was to investigate heart/muscle specific and inflammation related miRs in plasma of individuals before, directly after, and 24 h after a marathon run and to analyze their relation to conventional biochemical, cardiovascular, and performance indexes. Male endurance athletes (n =14) were recruited for the study after performing a battery of cardiac functional tests. Blood samples were collected before, directly after, and 24 h after a public marathon run. miR-1, miR-133, miR-206, miR-499, miR-208b, miR-21, and miR-155 were measured using individual Taqman assays and normalized to Caenorhabditis elegans miR-39 (cel-39) spike-in control. Moreover, soluble cardiac, inflammatory, and muscle damage markers were determined. As a result, skeletal- and heart muscle-specific miRs showed a significant increase after the marathon. The strongest increase was observed for miR-206. Twenty-four hours after the run, only miR-499 and miR-208b were returned to preexercise levels, whereas the others were still enhanced. In contrast, miR-21 and -155 were not affected by exercise. miR-1, -133a, and -206 correlated to aerobic performance parameters such as maximum oxygen uptake (VO(2max)) and running speed at individual anaerobic lactate threshold (VIAS). miR-1 showed a moderate negative correlation with fractional shortening, whereas miR-133a was positively related to the thickness of intraventricular septum. None of the miRs correlated with cardiac injury markers such as troponin T, troponin I, and pro-brain natriuretic peptide. In conclusion, these findings suggest a potential role for muscle- and heart-specific miRs in cardiovascular adaptation processes after endurance exercise. Moreover, the specific correlation of miR-1, -133a, and -206 to performance parameters indicated their potential role as biomarkers of aerobic capacity.

Circulating micrornas as potential biomarkers of aerobic exercise capacity

PubMed Central

Viereck, Janika; Krüger, Karsten; Thum, Thomas

2013-01-01

Purpose microRNAs (miRs) are crucial intracellular mediators of various biological processes, also affecting the cardiovascular system. Recently, it has been shown that miRs circulate extracellularly in the bloodstream and that such circulating miRs change in response to physical activity. Therefore, the purpose of the current study was to investigate heart/muscle specific and inflammation related miRs in plasma of individuals before, directly after, and 24 h after a marathon run and to analyze their relation to conventional biochemical, cardiovascular, and performance indexes. Male endurance athletes (n =14) were recruited for the study after performing a battery of cardiac functional tests. Blood samples were collected before, directly after, and 24 h after a public marathon run. miR-1, miR-133, miR-206, miR-499, miR-208b, miR-21, and miR-155 were measured using individual Taqman assays and normalized to Caenorhabditis elegans miR-39 (cel-39) spike-in control. Moreover, soluble cardiac, inflammatory, and muscle damage markers were determined. As a result, skeletal- and heart muscle-specific miRs showed a significant increase after the marathon. The strongest increase was observed for miR-206. Twenty-four hours after the run, only miR-499 and miR-208b were returned to preexercise levels, whereas the others were still enhanced. In contrast, miR-21 and -155 were not affected by exercise. miR-1, -133a, and -206 correlated to aerobic performance parameters such as maximum oxygen uptake (V̇o2max) and running speed at individual anaerobic lactate threshold (VIAS). miR-1 showed a moderate negative correlation with fractional shortening, whereas miR-133a was positively related to the thickness of intraventricular septum. None of the miRs correlated with cardiac injury markers such as troponin T, troponin I, and pro-brain natriuretic peptide. In conclusion, these findings suggest a potential role for muscle- and heart-specific miRs in cardiovascular adaptation processes after endurance exercise. Moreover, the specific correlation of miR-1, -133a, and -206 to performance parameters indicated their potential role as biomarkers of aerobic capacity. PMID:24363306

The association between the chronic use of non-steroidal anti- inflammatory drugs and oxidative and inflammatory markers in the elderly.

PubMed

Ely, Luisa Scheer; Valle Gottlieb, Maria Gabriela; Engroff, Paula; Gomes, Irenio; Moresco, Rafael Noal; Tatsch, Etiane; Bochi, Guilherme Vargas; Morrone, Fernanda Bueno; De Carli, Geraldo Attilio

2014-01-01

Investigate the association between the chronic or occasional use of nonsteroidal anti-inflammatory drugs (NSAIDs) and plasma levels of oxidative and inflammatory markers in elderly at the Family Health Strategy in Brazil. It was a cross-sectional study of data collected from random elderly volunteers. A questionnaire including sociodemographic, health and medicine use data was administered. The blood levels of FRAP (ferric reducing ability of plasma), AOPP (plasma advanced oxidation protein products), MDA (malondialdehyde) and insulin were measured. The study sample comprised 758 elderly patients, of which 121 (15.96%) used NSAIDs. The mean age was 68.53 years and 68.41 for individuals who used NSAIDs occasionally and chronically, respectively. Gastric problems may be associated with the chronic or occasional use of NSAIDs (P = 0.042). Which indicates mean plasma levels of Insulin and HOMA-IR (Homeostasis Model Assessment Insulin Resistance) are increased in chronic use of NSAIDs and describes a statistical trend (P = 0.065) for the association of chronic NSAIDs use with the BMI (body mass index) of the subjects studied. This study suggests that there is no association between the chronic or occasional use of NSAIDs and oxidative and inflammatory markers. It is known that NSAIDs have innumerable adverse effects, but they can have some benefits. So, additional studies are needed to clarify whether NSAIDs are associated with these markers and whether they are related with their real consequences.

Comparing serum levels of cardiac biomarkers in cancer patients receiving chemotherapy and subjects with chronic periodontitis

PubMed Central

2012-01-01

Background Chronic periodontitis (CP) is a chronic inflammation associated with elevations of several inflammatory and cardiac markers. Studies implicated CP as one of the etiologies in coronary heart disease (CHD). Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil (5FU). The most severe cardiac complications are heart failure, arrhythmia and coronary heart disease (CHD). In this study, we compared the level of inflammatory factors and cardiac markers between chronic periodontitis patients and cancer patients receiving chemotherapy. Methods 108 blood samples of periodontally healthy subjects were obtained on random from Hong Kong Red Cross, and these represented the controlled population. Forty-four patients diagnosed with chronic periodontitis were recruited from the West China Hospital of Stomatology, Sichuan University. They have received scaling and root planning with mean pocket depths of 6.05 mm. Thirty breast cancer patients diagnosed with invasive ductal carcinoma from UNIMED Medical Institute, Hong Kong gave consent to participate in this study. They received 4 cycles of 500mg/m2 5-fluorouracil, 75 mg/m2 epirubicin and 500mg/m2 cyclophosphamide at a 3-week interval between each cycle. Peripheral venous blood from each group was taken for measurement of blood cells, inflammatory marker (P-selectin, high sensitvity C-reactive protein) and cardiac markers (troponin T; troponin I; N-terminal pro brain natriuretic peptide (Nt-proBNP) and Lactate dehydrogenase (LDH). Results The lymphocyte count was higher (p < 0.05) in periodontitis patients than the other two groups, and more neutrophils (p < 0.05) were seen in cancer patients receiving chemotherapy. The two test groups demonstrated higher levels (p < 0.01) of inflammatory and cardiac markers than the control group. Conclusions The elevated cardiac markers found in periodontitis patients suggested that they may carry potential risks in developing cardiac lesions. Troponin T, troponin I, pro-BNP, LDH and high sensitvity C-reactive protein may be used as markers to monitor cardiac lesions in chronic inflammatory patients. PMID:23046680

Effect of obesity and metabolic syndrome on severity, quality of life, sleep quality and inflammatory markers in patients of asthma in India.

PubMed

Singh, Mandeep; Gupta, Nitesh; Kumar, Raj

2016-01-01

The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients. 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study. The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p< 0.05), decreased lung volumes (FRC) (p< 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients. The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury.

PubMed

Kumar, Raj G; Rubin, Jonathan E; Berger, Rachel P; Kochanek, Patrick M; Wagner, Amy K

2016-03-01

Studies have characterized absolute levels of multiple inflammatory markers as significant risk factors for poor outcomes after traumatic brain injury (TBI). However, inflammatory marker concentrations are highly inter-related, and production of one may result in the production or regulation of another. Therefore, a more comprehensive characterization of the inflammatory response post-TBI should consider relative levels of markers in the inflammatory pathway. We used principal component analysis (PCA) as a dimension-reduction technique to characterize the sets of markers that contribute independently to variability in cerebrospinal (CSF) inflammatory profiles after TBI. Using PCA results, we defined groups (or clusters) of individuals (n=111) with similar patterns of acute CSF inflammation that were then evaluated in the context of outcome and other relevant CSF and serum biomarkers collected days 0-3 and 4-5 post-injury. We identified four significant principal components (PC1-PC4) for CSF inflammation from days 0-3, and PC1 accounted for the greatest (31%) percentage of variance. PC1 was characterized by relatively higher CSF sICAM-1, sFAS, IL-10, IL-6, sVCAM-1, IL-5, and IL-8 levels. Cluster analysis then defined two distinct clusters, such that individuals in cluster 1 had highly positive PC1 scores and relatively higher levels of CSF cortisol, progesterone, estradiol, testosterone, brain derived neurotrophic factor (BDNF), and S100b; this group also had higher serum cortisol and lower serum BDNF. Multinomial logistic regression analyses showed that individuals in cluster 1 had a 10.9 times increased likelihood of GOS scores of 2/3 vs. 4/5 at 6 months compared to cluster 2, after controlling for covariates. Cluster group did not discriminate between mortality compared to GOS scores of 4/5 after controlling for age and other covariates. Cluster groupings also did not discriminate mortality or 12 month outcomes in multivariate models. PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0-3 post-TBI may distinguish individuals with poor 6-month outcome, and future studies should prospectively validate these findings. PCA of inflammatory mediators after TBI could aid in prognostication and in identifying patient subgroups for therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis

PubMed Central

Kellum, John A.; Kong, Lan; Fink, Mitchell P.; Weissfeld, Lisa A.; Yealy, Donald M.; Pinsky, Michael R.; Fine, Jonathan; Krichevsky, Alexander; Delude, Russell L.; Angus, Derek C.

2015-01-01

Background Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of pro-inflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8–39.0) (P<.001). Conclusions The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and mortality is highest when both proinflammatory and anti-inflammatory cytokine levels are high. PMID:17698689

Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country.

PubMed

Backer, Vibeke; Baines, Katherine J; Powell, Heather; Porsbjerg, Celeste; Gibson, Peter G

2016-02-01

An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue inflammation can be modified by migration and diet. To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). Of the 1059 Greenlandic Inuit participants, 556 were living in Greenland and 6.4% had asthma. Asthma was increased in Denmark (9%) compared to Greenland (3.6%, p < 0.0001) and associated with increased adipose tissue IL-6 gene expression and increased BMI. There was no association between asthma and adipose tissue mast cell gene expression. Pro-inflammatory gene expression (IL-6, IL-1β) was higher in those living in Denmark, and with increasing BMI and dietary changes. The anti-inflammatory (M2) macrophage marker, CD163, was higher in Greenland-dwelling Inuit (p < 0.01). No association was found between gene expression of mast cell markers in adipose tissue and asthma. Among Greenlandic Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.

PubMed

Mahon, K L; Lin, H-M; Castillo, L; Lee, B Y; Lee-Ng, M; Chatfield, M D; Chiam, K; Breit, S N; Brown, D A; Molloy, M P; Marx, G M; Pavlakis, N; Boyer, M J; Stockler, M R; Daly, R J; Henshall, S M; Horvath, L G

2015-04-14

Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1β, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.

Formula milk feeding does not increase the release of the inflammatory marker calprotectin, compared to human milk.

PubMed

Rosti, L; Braga, M; Fulcieri, C; Sammarco, G; Manenti, B; Costa, E

2011-01-01

Calprotectin is a protein released into stools, used as a marker of inflammation in inflammatory bowel diseases. We tested the hypothesis that cow's milk protein in formula milk may increase the intestinal release of calprotectin, as a consequence of a subclinical inflammatory reaction. At 12 weeks of age, we measured fecal calprotectin by an immunoenzyme assay (Calprest, Eurospital, Trieste, Italy), in 38 exclusively breastfed and in 32 exclusively formula-fed infants. Fecal calprotectin levels were not different in the two groups (p = 0.09), although a trend to higher values in infants with colic, or with family history of allergies was noted. This suggest that, in general, formula milk does not promote activation of an intestinal inflammatory reaction, compared to human milk, although a subclinical activation of the inflammatory response in infants at risk for allergic diseases may be present.

Inverse Relationship of the CMKLR1 Relative Expression and Chemerin Serum Levels in Obesity with Dysmetabolic Phenotype and Insulin Resistance

PubMed Central

Corona-Meraz, Fernanda-Isadora; Navarro-Hernández, Rosa-Elena; Ruíz-Quezada, Sandra-Luz; Madrigal-Ruíz, Perla-Monserrat; Castro-Albarrán, Jorge; Chavarría-Ávila, Efraín; Guzmán-Ornelas, Milton-Omar; Gómez-Bañuelos, Eduardo; Petri, Marcelo-Herón; Ramírez-Cedano, Joel-Isidro; Aguilar-Aldrete, María-Elena; Ríos-Ibarra, Clara; Vázquez-Del Mercado, Mónica

2016-01-01

Background. In obesity there is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. Chemerin is secreted in white adipose tissue and promotes low-grade inflammatory process, where it expressed CMKLR1 receptor. The role of chemerin and CMKLR1 in inflammatory process secondary to obesity is not defined yet. Methods. Cross-sectional study with 134 individuals classified as with and without obesity by body mass index (BMI) and IR. Body fat storage measurements and metabolic and inflammatory markers were measured by routine methods. Soluble chemerin and basal levels of insulin by ELISA and relative expression of CMKLR1 were evaluated with qPCR and 2−ΔΔCT method. Results. Differences (P < 0.05) were observed between obesity and lean individuals in body fat storage measurements and metabolic-inflammatory markers. Both CMKLR1 expression and chemerin levels were increased in obesity without IR. Soluble chemerin levels correlate with adiposity and metabolic markers (r = 8.8% to 38.5%), P < 0.05. Conclusion. The increment of CMKLR1 expression was associated with insulin production. Increased serum levels of chemerin in obesity were observed, favoring a dysmetabolic response. The results observed in this study suggest that both chemerin and CMKLR1 have opposite expression in the context of low-grade inflammatory response manifested in the development of IR. PMID:27239101

Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study

PubMed Central

2010-01-01

Background Fruits and vegetables are important sources of fiber and nutrients with a recognized antioxidant capacity, which could have beneficial effects on the proinflammatory status as well as some metabolic syndrome and cardiovascular disease features. The current study assessed the potential relationships of fruit and vegetable consumption with the plasma concentrations and mRNA expression values of some proinflammatory markers in young adults. Methods One-hundred and twenty healthy subjects (50 men/70 women; 20.8 ± 2.6 y; 22.3 ± 2.8 kg/m2) were enrolled. Experimental determinations included anthropometry, blood pressure and lifestyle features as well as blood biochemical and inflammatory measurements. The mRNA was isolated from peripheral blood mononuclear cells (PBMC) and the gene expression concerning selected inflammatory markers was assessed by quantitative real-time PCR. Nutritional intakes were estimated by a validated semi-quantitative food-frequency questionnaire. Results The highest tertile of energy-adjusted fruit and vegetable consumption (>660 g/d) was associated with lower plasma concentrations of C-reactive protein (CRP) and homocysteine and with lower ICAM1, IL1R1, IL6, TNFα and NFκB1 gene expression in PBMC (P for trend < 0.05), independently of gender, age, energy intake, physical activity, smoking, body mass index, systolic blood pressure and circulating non-esterified fatty acids. In addition, plasma CRP, homocysteine and TNFα concentrations and ICAM1, TNFα and NFκB1 gene expression in PBMC showed a descending trend as increased fiber intake (>19.5 g/d) from fruits and vegetables (P for trend < 0.05). Furthermore, the participants within the higher tertile (>11.8 mmol/d) of dietary total antioxidant capacity showed lower plasma CRP and mRNA values of ICAM1, IL1R1, IL6, TNFα and NFκB1 genes (P for trend < 0.05). The inverse association between fruit and vegetable consumption and study proinflammatory markers followed the same trend and remained statistically significant, after the inclusion of other foods/nutrients in the linear regression models. Conclusion A higher fruit and vegetable consumption was independently associated not only with reduced CRP and homocysteine concentrations but also with a lower mRNA expression in PBMC of some relevant proinflammatory markers in healthy young adults. PMID:20465828

Phytochemical Analysis on Quantification and the Inhibitory Effects on Inflammatory Responses from the Fruit of Xanthii fructus

PubMed Central

Yoo, Sae-Rom; Seo, Chang-Seob; Lee, Na-Ri; Shin, Hyeun-Kyoo; Jeong, Soo-Jin

2015-01-01

Objective: Xanthii fructus (Compositae) is a traditional herbal medicine used for treating headache, toothache, pruritus, empyema, and rhinitis. In this study of the quality control of X. fructus, we performed simultaneous analysis of nine marker compounds: Protocatechuic acid (1), chlorogenic acid (2), caffeic acid (3), 4,5-dicaffeoylquinic acid (4), ferulic acid (5), 3,5-dicaffeoylquinic acid (6), 1,3-dicaffeoylquinic acid (7), 1,4-dicaffeoylquinic acid (8), and 4,5-dicaffeoylquinic acid (9). Materials and Methods: Nine components were separated using reversed-phase SunFire™ C18 analytical column and analyzed using high-performance liquid chromatography. We examined the biological effects of the nine marker compounds by determining their anti-inflammatory activities in the murine macrophage cell line RAW 264.7. Results: Among the nine marker compounds, eight significantly inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-α) production. 1, 3, 5 had significant inhibitory effects on LPS-induced prostaglandin E2 (PGE2) production in RAW 264.7 cells. None of the tested marker compounds had a significant effect on interleukin-6 production in LPS-treated RAW 264.7 cells. Our data demonstrated that each marker compound from X. fructus exerts anti-inflammatory activity by targeting different inflammation-related pathways such as the TNF-α or PGE2 pathway. Conclusion: Further experiments using in vitro and in vivo models are needed to identify the mechanisms responsible for the anti-inflammatory properties of each marker compound. SUMMARY Simultaneous analysis of nine phenylpropanoids in the Xanthii fructus was established using HPLC-PDA system.1,4-dicaffeoylquinic acid significantly inhibited LPS-stimulated TNF-a production.Protocatechuic acid, caffeic acid and ferulic acid had significant inhibitory effects on LPS-induced PGE2 production in RAW 264.7 cells. PMID:27013799

Retinal vascular changes are a marker for cerebral vascular diseases

PubMed Central

Moss, Heather E.

2016-01-01

The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

The Relations Between Immunity, Oxidative Stress and Inflammation Markers, in Childhood Obesity.

PubMed

Laura Anca, Popescu; Bogdana, Virgolici; Olivia, Timnea; Horia, Virgolici; Dumitru, Oraseanu; Leon, Zagrean

2014-10-01

Oxidative stress, inflammation and insulin resistance are the principal culprits in childhood obesity. Immune modifications are also important in the development of the obesity complications.The aim of this study is to find the relations for some immunity parameters with markers for oxidative stress and inflammation. Sixty obese children (10-16 years old) and thirty age and sex matched lean children were involved. The activities for erythrocyte superoxid dismutase (SOD), for erythrocyte glutathione peroxidase (GPx) and serum thioredoxin level were measured by ELISA, as oxidative stress markers. Circulating immune complexes (CIC), complement fractions C3, C4 and the self-antibodies, antismooth muscle antibodies (ASMA), antiliver-kidney microsome antibodies (LKM1) were measured by ELISA methods. Ceruloplasmin, haptoglobin and C reactive protein (CRP) were measured as inflammatory markers by immunoturbidimetric methods. ceruloplasmin (p<0.001), haptoglobin (p<0.001), CRP (p<0.05) and activity for SOD (p<0.001) were measured, while thioredoxin concentration (p<0.04) was reduced. The antibodies LKM1 and ASMA and GPx activity were not modified between groups. Positive correlations (for p<0.05) were calculated between SOD activity and LKM1 (r=0.37), GPx activity and ASMA (r=0.27), haptoglobin and C3 (r=0.33), ceruloplasmin and CIC (r=0.41), CRP and C3 (p<0.27) and negative correlations were calculated for C4 both with GPx activity (r= -0.28) and with thioredoxin level (r= -0.27). In the obese children versus the lean ones, higher levels for C3 (p<0.001), C4(p<0.001), CIC (p<0.05), In conclusion, this study demonstrates that immune modifications, inflammation and oxidative stress are related and they act in cluster in childhood obesity. Copyright © 2014. Published by Elsevier Inc.

Consumption of mixed fruit-juice drink and vitamin C reduces postprandial stress induced by a high fat meal in healthy overweight subjects.

PubMed

Peluso, Ilaria; Villano, Debora V; Roberts, Susan A; Cesqui, Eleonora; Raguzzini, Anna; Borges, Gina; Crozier, Alan; Catasta, Giovina; Toti, Elisabetta; Serafini, Mauro

2014-01-01

Postprandial stress induced by acute consumption of meals with a high fat content results in an increase of markers of cardiometabolic risk. Repeated acute dietary stress may induce a persistent low-grade inflammation, playing a role in the pathogenesis of functional gut diseases. This may cause an impairment of the complex immune response of the gastrointestinal mucosa, which results in a breakdown of oral tolerance. We investigated the effect of ingestion of a fruit-juice drink (FJD) composed by multiple fruit juice and extracts, green tea extracts and vitamin C on postprandial stress induced by a High Fat Meal (HFM) in healthy overweight subjects. Following a double blind, placebo controlled, cross-over design, 15 healthy overweight subjects were randomized to a HFM providing 1334 Kcal (55% fat, 30% carbohydrates and 15% proteins) in combination with 500 mL of a placebo drink (HFM-P) or a fruit-juice drink (HFM-FJD). Ingestion of HFM-P led to an increase in circulating levels of cholesterol, triglycerides, glucose, insulin, TNF-α and IL-6. Ingestion of HFM-FJD significantly reduced plasma levels of cholesterol and triglycerides, decreasing inflammatory response mediated by TNF-α and IL-6. Ingestion of a fruit-juice drink reduce markers of postprandial stress induced by a HFM.

Label-free counting of circulating cells by in vivo photoacoustic flow cytometry

NASA Astrophysics Data System (ADS)

Zhou, Quanyu; Yang, Ping; Wang, Qiyan; Pang, Kai; Zhou, Hui; He, Hao; Wei, Xunbin

2018-02-01

Melanoma, developing from melanocytes, is the most serious type of skin cancer. Circulating melanoma cells, the prognosis marker for metastasis, are present in the circulation at the early stage. Thus, quantitative detection of rare circulating melanoma cells is essential for monitoring tumor metastasis and prognosis evaluation. Compared with in vitro assays, in vivo flow cytometry is able to identify circulating tumor cells without drawing blood. Here, we built in vivo photoacoustic flow cytometry based on the high absorption coefficient of melanoma cells, which is applied to labelfree counting of circulating melanoma cells in tumor-bearing mice.

Positive correlation between inflammation on sacroiliac joint MRI and serum C-terminal telopeptide of type-I collagen in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis.

PubMed

Kang, Kwi Young; Jung, Joon-Yong; Hong, Yeon Sik; Ju, Ji Hyeon; Park, Sung-Hwan

2017-01-01

To identify the clinical disease activity scores and laboratory markers that best reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). This cross-sectional study included all consecutive patients who presented with axial spondyloarthritis in 2013-2015. All underwent SIJ MRI. The bone marrow oedema in the inflammatory lesions on MRI was scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide of type-I collagen (sCTX-I), and inflammatory markers were measured. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were assessed. The correlations between the MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables were evaluated. Of the 81 patients with axSpA, 45 had AS and 36 had nr-axSpA. The AS and nr-axSpA groups did not differ in terms of disease activity scores, physical functional index, or MRI-determined SIJ inflammation. Erythrocyte sedimentation rate, C-reactive protein, and ASDAS correlated with MRI inflammatory scores in nr-axSpA but not in AS. sCTX-I correlated with MRI-determined SIJ inflammatory scores in AS only. BASDAI and BALP levels did not associate with MRI inflammatory scores in either group. Multivariate analysis showed that sCTX-I associated independently with MRI inflammatory score in AS (β=17.047, p=0.038). Inflammatory markers and ASDAS correlated with active sacroiliitis on MRI in nr-axSpA only. In AS, only sCTX-I correlated with active inflammation on SIJ MRI. sCTX-I may be useful as a marker of objective inflammation in AS.

Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

PubMed

Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

2016-01-01

Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

Low dose aspirin increases 15-epi-lipoxin A4 levels in diabetic chronic kidney disease patients.

PubMed

Goicoechea, Marian; Sanchez-Niño, Maria Dolores; Ortiz, Alberto; García de Vinuesa, Soledad; Quiroga, Borja; Bernis, Carmen; Morales, Enrique; Fernández-Juarez, Gema; de Sequera, Patricia; Verdalles, Ursula; Verde, Eduardo; Luño, José

2017-10-01

Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15-epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients. Open label randomized clinical trial. 50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months. Aspirin (100mg/day) or standard treatment. To analyze the effect of aspirin on plasma 15-epi-LXA4 levels and inflammatory markers in CKD patients. Baseline plasma15-epi-LXA4 levels were lower in diabetic (1.22 ± 0.99ng/ml) than in non-diabetic CKD patients (2.05 ± 1.06ng/ml, p < 0.001) and inversely correlated with glycosylated hemoglobin levels (r = -0.303, p = 0.006). In multivariate analysis, diabetes was associated with lower 15-epi-LXA4 levels, adjusted for age, inflammatory markers and renal function (p = 0.005). In the whole study population, 15-epi-LXA4 levels tended to increase, but not significantly (p = 0.45), after twelve months on aspirin (from mean ± SD 1.84 ± 1.06 to 2.04 ± 0.75ng/ml) and decreased in the standard care group (1.60 ± 1.15 to 1.52 ± 0.68ng/ml, p = 0.04). The aspirin effect on 15-epi-LXA4 levels was more striking in diabetic patients, increasing from 0.94 ± 0.70 to 1.93 ± 0.74ng/ml, p = 0.017. Diabetic patients with CKD have lower circulating 15-epi-LXA4 levels than non-diabetic CKD patients. Low dose aspirin for 12 months increased 15-epi-LXA4 levels in diabetic patients. Given its anti-inflammatory properties, this increase in 15-epi-LXA4 levels may contribute to the beneficial effects of low dose aspirin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Weight loss and vascular inflammatory markers in overweight women with and without polycystic ovary syndrome.

PubMed

Moran, Lisa J; Noakes, Manny; Wittert, Gary A; Clifton, Peter M; Norman, Robert J

2012-11-01

Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular disease risk. The effect of weight loss on the vascular inflammatory markers plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1) and intracellular adhesion molecule-1 (sICAM-1) is unknown. Overweight women with (n=14) and without (n=13) PCOS of comparable age and body mass index undertook an 8-week weight-loss programme. Women with PCOS had elevated PAI-1, sVCAM-1 and sICAM-1 before and after weight loss compared with the controls. For all women, sVCAM-1 (P=0.026) and sICAM-1 (P=0.04) decreased with weight loss. Women with PCOS have elevated inflammatory markers, which are partially reduced by weight loss. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Cocoa Polyphenols and Inflammatory Markers of Cardiovascular Disease

PubMed Central

Khan, Nasiruddin; Khymenets, Olha; Urpí-Sardà, Mireia; Tulipani, Sara; Garcia-Aloy, Mar; Monagas, María; Mora-Cubillos, Ximena; Llorach, Rafael; Andres-Lacueva, Cristina

2014-01-01

Epidemiological studies have demonstrated the beneficial effect of plant-derived food intake in reducing the risk of cardiovascular disease (CVD). The potential bioactivity of cocoa and its polyphenolic components in modulating cardiovascular health is now being studied worldwide and continues to grow at a rapid pace. In fact, the high polyphenol content of cocoa is of particular interest from the nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to possess a range of cardiovascular-protective properties, and can play a meaningful role through modulating different inflammatory markers involved in atherosclerosis. Accumulated evidence on related anti-inflammatory effects of cocoa polyphenols is summarized in the present review. PMID:24566441

Elevated Endomyocardial Biopsy Macrophage-Related Markers in Intractable Myocardial Diseases.

PubMed

Hayashi, Yuka; Hanawa, Haruo; Jiao, Shuang; Hasegawa, Go; Ohno, Yukako; Yoshida, Kaori; Suzuki, Tomoyasu; Kashimura, Takeshi; Obata, Hiroaki; Tanaka, Komei; Watanabe, Tohru; Minamino, Tohru

2015-12-01

Tissue macrophages can be activated by endogenous danger signals released from cells that are stressed or injured, leading to infiltration of inflammatory macrophages and neutrophils. We postulated that macrophage-related markers might be closely associated with the existence of endogenous danger signals, reflecting ongoing tissue injury in the absence of foreign substances. This study was designed to assess the ability of macrophage-related markers in endomyocardial biopsies to predict ongoing cardiac injury in non-inflammatory myocardial diseases. We examined levels of macrophage-related markers (CD68, CD163, CD45) in endomyocardial biopsies from patients (n = 86) with various myocardial diseases by quantitative reverse transcription-polymerase chain reaction (n = 78) and immunohistochemistry (n = 56). Thirty-three patients without inflammatory cardiac disease such as myocarditis and sarcoidosis were classified as "improved" or "non-improved" defined as a 10% increase in left ventricular ejection fraction by echocardiograph and a value greater than 30% at the time of follow-up. All macrophage-related (MacR) markers levels were not higher in non-improved dilated cardiomyopathy (DCM) patients than improved patients. However, patients with cardiac amyloidosis, cardiac Fabry disease, mitochondrial cardiomyopathy, and biventricular arrhythmogenic right ventricular cardiomyopathy (ARVC), which were categorized as "non-improvement diseases," had elevated macrophage-related markers compared to improved patients. Macrophage-related markers levels were increased in endomyocardial biopsy samples of patients with intractable myocardial diseases such as amyloidosis, mitochondrial disease, Fabry disease, and biventricular ARVC.

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis.

PubMed

Choi, Ivy Y; Karpus, Olga N; Turner, Jason D; Hardie, Debbie; Marshall, Jennifer L; de Hair, Maria J H; Maijer, Karen I; Tak, Paul P; Raza, Karim; Hamann, Jörg; Buckley, Christopher D; Gerlag, Danielle M; Filer, Andrew

2017-01-01

Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers. We observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables. Stromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.

Associations between dietary fiber and inflammation, hepatic function, and risk of type 2 diabetes in older men: potential mechanisms for the benefits of fiber on diabetes risk.

PubMed

Wannamethee, S Goya; Whincup, Peter H; Thomas, Mary C; Sattar, Naveed

2009-10-01

To examine the relationship between dietary fiber and the risk of type 2 diabetes in older men and the role of hepatic and inflammatory markers. The study was performed prospectively and included 3,428 nondiabetic men (age 60-79 years) followed up for 7 years, during which there were 162 incident cases of type 2 diabetes. Low total dietary fiber (lowest quartile < or =20 g/day) was associated with increased risk of diabetes after adjustment for total calorie intake and potential confounders (relative risk -1.47 [95% CI 1.03-2.11]). This increased risk was seen separately for both low cereal and low vegetable fiber intake. Dietary fiber was inversely associated with inflammatory markers (C-reactive protein, interleukin-6) and with tissue plasminogen activator and gamma-glutamyl transferase. Adjustment for these markers attenuated the increased risk (1.28 [0.88-1.86]). Dietary fiber is associated with reduced diabetes risk, which may be partly explained by inflammatory markers and hepatic fat deposition.

Liquid biopsy: a step forward towards precision medicine in urologic malignancies.

PubMed

Di Meo, Ashley; Bartlett, Jenni; Cheng, Yufeng; Pasic, Maria D; Yousef, George M

2017-04-14

There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.

Decreased number of steroid receptors of circulating lymphocytes in Crohn's disease and ulcerative colitis.

PubMed

Krasznai, A; Krajcsi, P; Arányi, P; Mészáros, K; Horváth, I

1986-01-01

The number of steroid receptors of circulating lymphocytes was determined in 13 patients with inflammatory bowel disease and in controls. Marked reduction of the number of receptors was observed both in Crohn's disease and in ulcerative colitis; no receptors were detected by radioactive hormone binding assay in 4 cases.

Of Microbes and Meals: The Health Consequences of Dietary Endotoxemia

PubMed Central

Kelly, Caleb J.; Colgan, Sean P.; Frank, Daniel N.

2014-01-01

The human intestinal tract is comprised of a rich and complex microbial ecosystem. This intestinal microbota provides a large reservoir of potentially toxic molecules, including bacterial endotoxin (i.e., lipopolysaccharide). This potent inflammatory molecule is detectable in the circulation of healthy individuals and levels transiently increase following ingestion of energy rich meals. Chronic exposure to circulating endotoxin has been associated with obesity, diabetes, and cardiovascular disease. Western-style meals augment LPS translocation and by this mechanism may contribute to the pathogenesis of these diseases. By contrast, the gut and other organs have evolved mechanisms to detoxify endotoxin and to neutralize the potentially inflammatory qualities of circulating endotoxin. Of specific interest to clinicians is evidence that acute postprandial elevation of circulating endotoxin is dependent on meal composition. In this review we present an overview of the biochemical and cellular mechanisms that lead to endotoxemia, with emphasis on the interplay between microbial and nutritional determinants of this condition. The link between endotoxemia, diet, and changes in the intestinal microbiota raise the possibility that dietary interventions can, at least in part, ameliorate the detrimental outcomes of endotoxemia. PMID:22378797

The predictive effect of inflammatory markers and lipid accumulation product index on clinical symptoms associated with polycystic ovary syndrome in nonobese adolescents and younger aged women.

PubMed

Tola, Esra Nur; Yalcin, Serenat Eris; Dugan, Nadiye

2017-07-01

The aim of our study is to analyse the inflammatory markers and lipid accumulation product (LAP) index in nonobese adolescents and younger aged women with polycystic ovary syndrome (PCOS) compared with age and body mass index (BMI)-matched healthy controls and to determine whether the investigated parameters are potential markers for the etiopathogenesis of PCOS. We also aim to determine whether these inflammatory markers are predictive for developing some clinical implications, such as cardiovascular disease (CVD) and insulin resistance (IR), associated with PCOS. A total of 34 adolescents and younger aged females with PCOS, and 33 age and BMI-matched healthy controls were recruited for our study. All participants were nonobese (BMI<25). Neopterin (NEO), C-reactive protein (CRP) levels and complete blood parameters were assessed. LAP index and homeostasis model assessment of IR (HOMA-IR) were calculated; anthropometric, clinical and biochemical parameters were also recorded. Serum NEO, CRP levels and LAP index were significantly increased in nonobese adolescents and younger aged females with PCOS compared to healthy controls. We could not found any predictive effect of investigated inflammatory markers and LAP index on CVD risk among PCOS patients after adjustment for abdominal obesity. We also found a positive predictive effect of WBC and a negative predictive effect of lymphocytes on IR in PCOS patients after adjustment for abdominal obesity. We did not find any predictor effect of NEO on IR, but it was a positive predictive marker for an elevated HOMA-IR index. Elevated NEO, CRP levels and LAP index could have potential roles in the etiopathogenesis of PCOS in nonobese adolescents and younger aged females,NEO could be a predictive marker for elevated HOMA-IR index, and WBC and lymphocytes could be predictive for the development of IR among nonobese adolescents and younger aged females with PCOS. Copyright © 2017 Elsevier B.V. All rights reserved.

Waist-to-height ratio as a marker of low-grade inflammation in obese children and adolescents.

PubMed

Caminiti, Carolina; Armeno, Marisa; Mazza, Carmen S

2016-05-01

The epidemic of childhood obesity is associated with early atherosclerosis. Several reports have related this event to low-grade inflammation described in obesity. CRP and IL6 are markers that correlate with adiposity. The waist-to-height ratio (WtHR) is an anthropometric marker associated with insulin resistance and inflammation. The objective of this study was to assess the correlation between WtHR, metabolic complications and pro-inflammatory factors in obese children and adolescents. Weight, height, waist circumference, glycemia, insulin, CRP, TNF-α and IL-6 were measured in the baseline sample in 280 patients 6-19 years of age with overweight or obesity (OW/OB) and 112 normal-weight controls. Logistic regression was performed using WtHR as an independent variable. p>0.05 STATA11. Mean WtHR was 0.6±0.06 in OW/OB and 0.43±0.02 in controls (p<0.01). WtHR was increased in 93% of the OW/OB vs. 2% of the controls. In the OW/OB inflammatory markers were significantly increased (p<0.01) compared to the controls (CRP 2.2 vs. 0.8; Il-6 2.9 vs. 2.1; and TNF-α 6.2 vs. 5.5). In the WtHR>0.5, insulin resistence and inflammatory markers were significantly increased (p<0.01) compared to the WtHR<0.5 (HOMA 3.4 vs. 1.4; CRP 2.3 vs. 0.6; Il-6 2.9 vs. 2.1; and TNF-α 6.4 vs. 5.55). In logistic regression, a significant independent association was found between WtHR with CRP (OR1.47), IL6 (OR1.60) and TNF-α (OR1.79). Obese children and adolescents have high inflammatory markers that may increase cardiovascular risk. WtHR is associated with low-grade inflammation and may be considered a relevant anthropometric marker in the clinical practice.

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses.

PubMed

Aho, Vilma; Ollila, Hanna M; Kronholm, Erkki; Bondia-Pons, Isabel; Soininen, Pasi; Kangas, Antti J; Hilvo, Mika; Seppälä, Ilkka; Kettunen, Johannes; Oikonen, Mervi; Raitoharju, Emma; Hyötyläinen, Tuulia; Kähönen, Mika; Viikari, Jorma S A; Härmä, Mikko; Sallinen, Mikael; Olkkonen, Vesa M; Alenius, Harri; Jauhiainen, Matti; Paunio, Tiina; Lehtimäki, Terho; Salomaa, Veikko; Orešič, Matej; Raitakari, Olli T; Ala-Korpela, Mika; Porkka-Heiskanen, Tarja

2016-04-22

Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.

Triticum vulgare extract exerts an anti-inflammatory action in two in vitro models of inflammation in microglial cells

PubMed Central

Sanguigno, Luca; Casamassa, Antonella; Funel, Niccola; Minale, Massimiliano; Riccio, Rodolfo; Riccio, Salvatore; Boscia, Francesca; Brancaccio, Paola; Pollina, Luca Emanuele; Anzilotti, Serenella; Di Renzo, Gianfranco

2018-01-01

Triticum vulgare has been extensively used in traditional medicine thanks to its properties of accelerating tissue repair. The specific extract of Triticum vulgare manufactured by Farmaceutici Damor (TVE-DAMOR) is already present in some pharmaceutical formulations used in the treatment of decubitus ulcers, skin lesions and burns. It has been recently suggested that this Triticum vulgare extract may possess potential anti-inflammatory properties. In the light of these premises the aim of the present paper was to verify the anti-inflammatory role of TVE, using the LPS-stimulated microglia model of inflammation. In particular the effect of different concentrations of TVE on the release of several mediators of inflammation such as nitric oxide, IL-6, PGE2 and TNF alpha was evaluated. More important, the anti-inflammatory effect of TVE was confirmed also in primary rat microglia cultures. The results of the present study show that TVE exerts anti-inflammatory properties since it reduces the release of all the evaluated markers of inflammation, such as NO, IL6, TNF alpha and PGE2 in LPS-activated BV2 microglial cells. Intriguingly, TVE reduced microglia activation and NO release also in primary microglia. Indeed, to verify the pathway of modulation of the inflammatory markers reported above, we found that TVE restores the cytoplasmic expression of p65 protein, kwown as specific marker associated with activation of inflammatory response. The evidence for an inhibitory activity on inflammation of this specific extract of Triticum vulgare may open the way to the possibility of a therapeutical use of the Triticum vulgare extract as an anti-inflammatory compound in certain pathological states such as burns, decubitus ulcers, folliculitis and inflammation of peripheral nerve. PMID:29902182

Wound healing potentials of Thevetia peruviana: Antioxidants and inflammatory markers criteria.

PubMed

Rahman, Nazneen; Rahman, Haseebur; Haris, Mir; Mahmood, Riaz

2017-10-01

Thevetia peruviana is a medicinal plant used in the treatment of external wounds, infected area, ring worms, tumours etc. in traditional system of medicine. The aim of the study was to evaluate the wound healing potentials of T. peruviana leaves hexane (LH) and fruit rind (FW) water extracts and to prove the folkloric claims. The antimicrobial, antioxidant and anti-inflammatory potentials could be important strategies in defining potent wound healing drug. Based on these approaches the current study was designed using incision, excision and dead space wound models with the biochemical, antioxidant enzymes and inflammatory marker analysis. The fruit rind water extract showed highest WBS of 1133 ± 111.4 g. The extracts in excision model retrieved the excised wound i.e. complete healing of wound at day 14. The hydroxyproline content of FW and LH treated dry granuloma tissue was increased to 65.73 ± 3.2 mg/g and 53.66 ± 0.38 mg/g, accompanied by elevations of hexosamine and hexauronic acid with upregulation of GSH, catalase, SOD, peroxidase and the down regulation of the inflammatory marker (NO) and oxidative stress marker (LPO) in wet granulation tissue was documented. Conclusively, both the extracts showed enhanced WBS, rate of wound contraction, skin collagen tissue development, and early epithelisation. Therapeutic wound healing effect was further proven by reduced free radicals and inflammatory makers associated with enhanced antioxidants and connective tissue with histological evidence of more collagen formation. The present research could establish T. peruviana as potential source of effective wound healing drugs.

Quantitative analysis of blood cells and inflammatory factors in wounds.

PubMed

Cerveró-Ferragut, S; López-Riquelme, N; Martín-Tomás, E; Massa-Domínguez, B; Pomares-Vicente, J; Soler-Pérez, M; Sánchez-Hernández, J F

2017-03-02

The aim of this study was to quantify blood cells and inflammatory markers, involved in the healing process, in exudates from wounds in different healing phases, to assess these markers in order to identify the inflammatory phase of the wounds. Patients who presented with postsurgical wounds, which closed by first and second intention, and those who presented with pressure ulcers (PUs), which were closed by second intention, were included in the study. We examined wounds from 37 patients and collected samples from 52 wounds in the inflammatory phase, 30 in the proliferative phase and 29 in the maturation phase. The number of neutrophils and platelets in the exudate collected from wounds in the inflammatory phase was significantly higher (p<0.001), while the number of lymphocytes, was significantly lower in exudate from wounds in the inflammatory phase (p<0.001). Wound c-reactive protein (CRP) and immunoglobulin G (IgG) levels were higher in the inflammatory group (p<0.001). We found a significantly positive correlation between CRP levels and the percentage of neutrophils and monocytes (r=0.346, p=0.004; r=0.293, p=0.015), and a significantly negative correlation between CRP levels and the percentage of lymphocytes (r=-0.503, p<0.001). A stepwise logistic regression analysis was used to identify an optimal combination of these biomarkers. The optimal biomarker combinations were neutrophils + monocytes + platelets + IgG + CRP, with an area under the curve (AUC) of 0.981 [confidence interval (CI) 95%: 0.955-1.000, p<0.001] for the diagnosis of wounds in the inflammatory phase. The optimal cutpoint yielded 96.9 % sensitivity and 94.6 % specificity. The biomarker combination predicted the inflammatory phase and was superior to individual biomarkers. Our findings suggest that the combination of the markers, percentage of neutrophils and monocytes, platelets, CRP and IgG levels could be useful prognostic indicators of the inflammatory phase.

Increased Circulating FGF23 Does Not Lead to Cardiac Hypertrophy in the Male Hyp Mouse Model of XLH.

PubMed

Liu, Eva S; Thoonen, Robrecht; Petit, Elizabeth; Yu, Binglan; Buys, Emmanuel S; Scherrer-Crosbie, Marielle; Demay, Marie B

2018-05-01

Serum levels of fibroblast growth factor 23 (FGF23) markedly increase with renal impairment, with FGF23 levels correlating with the presence of left ventricular hypertrophy (LVH) and mortality in patients with chronic kidney disease (CKD). FGF23 activates calcineurin/nuclear factor of activated T cell (NFAT) signaling and induces hypertrophy in murine cardiomyocytes. X-linked hypophosphatemia (XLH) is characterized by high circulating levels of FGF23 but, in contrast to CKD, is associated with hypophosphatemia. The cardiac effects of high circulating levels of FGF23 in XLH are not well defined. Thus, studies were undertaken to define the cardiac phenotype in the mouse model of XLH (Hyp mice). Echocardiographic and histological analyses demonstrated that Hyp left ventricles (LVs) are smaller than those of wild-type mice. Messenger RNA expression of cardiac hypertrophy markers was not altered in the LV or right ventricle of Hyp mice. However, the Hyp LVs had increased expression of the NFAT target genes NFATc1 and RCAN1. To determine whether phosphate alone can induce markers of hypertrophy, differentiated C2C12 myocytes were treated with phosphate. Phosphate treatment increased expression of cardiac hypertrophy markers, supporting a primary role for phosphate in inducing LVH. Although previous studies showed that increased circulating FGF23 and phosphate levels are associated with LVH, our results demonstrated that in XLH, high circulating levels of FGF23 in the setting of hypophosphatemia do not induce cardiac hypertrophy.

Changes in Inflammatory and Bone Turnover Markers After Periodontal Disease Treatment in Patients With Diabetes.

PubMed

Izuora, Kenneth E; Ezeanolue, Echezona E; Neubauer, Michael F; Gewelber, Civon L; Allenback, Gayle L; Shan, Guogen; Umpierrez, Guillermo E

2016-06-01

The underlying mechanisms for increased osteopenia and fracture rates in patients with diabetes are not well understood, but may relate to chronic systemic inflammation. We assessed the effect of treating periodontal disease (POD), a cause of chronic inflammation, on inflammatory and bone turnover markers in patients with diabetes. Using an investigator-administered questionnaire, we screened a cross-section of patients presenting for routine outpatient diabetes care. We recruited 22 subjects with POD. Inflammatory and bone turnover markers were measured at baseline and 3 months following POD treatment (scaling, root planing and subantimicrobial dose doxycycline). There were nonsignificant reductions in high-sensitivity C-reactive protein (6.34-5.52mg/L, P = 0.626) and tumor necrosis factor-alpha (10.37-10.01pg/mL, P = 0.617). There were nonsignificant increases in urinary C-terminal telopeptide (85.50-90.23pg/mL, P = 0.684) and bone-specific alkaline phosphatase (7.45-8.79pg/mL, P = 0.074). Patients with >90% adherence with doxycycline were 6.4 times more likely to experience reduction in tumor necrosis factor-alpha (P = 0.021) and 2.8 times more likely to experience reductions in high-sensitivity C-reactive protein (P = 0.133). Treatment of POD in patients with diabetes resulted in nonsignificant lowering of inflammatory markers and nonsignificant increase in bone turnover markers. However, adherence to doxycycline therapy resulted in better treatment effects. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Serum leveis of inflammatory markers in type 2 diabetes patients with chronic periodontitis

PubMed Central

LONGO, Priscila Larcher; ARTESE, Hilana Paula Carillo; RABELO, Marianade Sousa; KAWAMOTO, Dione; FOZ, Adriana Moura; ROMITO, Giuseppe Alexandre; DIB, Sérgio Atala; MAYER, Marcia Pinto Alves

2014-01-01

Diabetes has been associated with periodontitis, but the mechanisms through which periodontal diseases affect the metabolic control remain unclear. Objective This study aimed to evaluate serum leveis of inflammatory markers, IL-8, IL-6 and monocyte chemoattractant protein 1 (MCP-1), in type 2 diabetic patients in the presence of chronic periodontitis. Material and Methods Forty two individuals were enrolled in this study and assigned to one of five groups: diabetes mellitus with inadequate glycemic control and periodontitis (DMI+P, n = 10), diabetes mellitus with adequate glycemic control and periodontitis (DMA+P, n = 10), diabetes mellitus without periodontitis (DM, n = 10), periodontitis without diabetes (P, n=6), and neither diabetes nor periodontitis (H, n = 6). Periodontal clinical examination included visible plaque index (PL), gingival bleeding index (GB), probing depth (PD), attachment level (AL) and bleeding on probing (BP). Glycemic control was evaluated by serum concentration of glycated hemoglobin (HbAlc). Inflammatory serum markers IL-8, IL-6 and (MCP-1) were measured by ELISA. Results DMI+P and DMA+P groups presented higher PD (p=0.025) and AL (p=0.003) values when compared to the P group. There were no significant differences among groups for IL-6, IL-8 and MCP-1 serum levels. Conclusions Although periodontitis was more severe in diabetic patients, the serum levels of the investigated inflammatory markers did not differ among the groups. PMID:24676580

Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury.

PubMed

Aisiku, Imo P; Yamal, Jose-Miguel; Doshi, Pratik; Benoit, Julia S; Gopinath, Shankar; Goodman, Jerry C; Robertson, Claudia S

2016-09-15

Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. NCT00313716 registered 4/2006.

Screening for the anti-inflammation quality markers of Xiaojin Pills based on HPLC-MS/MS method, COX-2 inhibition test and protein interaction network.

PubMed

Xiong, Xi; He, Ya-Nan; Feng, Bi; Pan, Yuan; Zhang, Hai-Zhu; Ke, Xiu-Mei; Zhang, Yi; Yang, Ming; Han, Li; Zhang, Ding-Kun

2018-05-10

Nowadays, breast disorders seriously affect women's health in an increasing number. In China, Xiaojin Pills are commonly used in the treatment of breast diseases. Doctors have concluded that the combined use of Xiaojin Pills with conventional therapy can significantly improve the efficacy with fewer side effects. However, the prescription of Xiaojin Pills is complicated and their quality control methods cannot completely ensure the quality of Xiaojin Pills. On the basis of its mechanism, our study combined chemical evaluation and biological evaluation to identify the anti-inflammatory markers of Xiaojin Pills. In this manuscript, 13 compounds in Xiaojin Pills were quantified. At the same time, the cyclooxygenase-2 inhibition rates of different Xiaojin Pills were measured and the possible markers were screened by spectrum-effect relationship. Further, anti-inflammatory activities of markers were verified and protein interaction network was analyzed, identifying the components of Protocatechuate, Beta-Boswellic acid and Levistilide A as the anti-inflammatory quality markers of Xiaojin Pills. We hope our studies can provide a scientific theoretical basis for accurately quality control of Xiaojin Pills and reasonable suggestions for pharmaceutical companies and new ideas for the quality control of other medicines.

Multimarker Quantitative Real-Time PCR Detection of Circulating Melanoma Cells in Peripheral Blood: Relation to Disease Stage in Melanoma Patients

PubMed Central

Koyanagi, Kazuo; Kuo, Christine; Nakagawa, Taku; Mori, Takuji; Ueno, Hideaki; Lorico, Arnulfo R.; Wang, He-Jing; Hseuh, Eddie; O’Day, Steven J.; Hoon, Dave S.B.

2010-01-01

Background Detection of melanoma cells in circulation may be important in assessing tumor progression. The objective of this study was to develop a specific, reliable, multimarker quantitative real-time reverse transcription-PCR (qRT) assay for detecting melanoma cells in patients’ blood. Methods We developed qRT assays for the mRNA of four melanoma-associated markers: MART-1, GalNAc-T, PAX-3, and MAGE-A3. In optimization studies, we tested 17 melanoma cell lines and 49 peripheral blood leukocyte (PBL) samples from volunteers. We performed RNA and melanoma cell dilution studies to assess the detection limits and imprecision of the assays. We measured the mRNAs in blood specimens from 94 melanoma patients [American Joint Committee on Cancer (AJCC) stage I, n = 20; II, n = 20; III, n = 32; IV, n = 22]. Results All markers were frequently detected in melanoma cell lines, whereas none of the markers was detected in PBLs from volunteers. The qRT assay could detect 1 melanoma cell in 107 PBLs in the melanoma cell-dilution studies. Markers were detected in 15%, 30%, 75%, and 86% of melanoma patients with AJCC stage I, II, III, and IV disease, respectively. The number of positive markers and AJCC stage were significantly correlated (Spearman correlation coefficient = 0.58; P <0.0001). Conclusions Multimarker qRT can detect circulating melanoma cells in blood. Measurement of the studied molecular markers in blood may be useful in detection of metastasis and monitoring treatment response of melanoma patients. PMID:15817820

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs

PubMed Central

2014-01-01

Background Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. Methods We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Results Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47 – 6.19) and (OR = 2.52, 95% CI = 1.45 – 4.35), (OR = 4.26, 95% CI = 2.39 – 7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12 – 0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Conclusion Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs. PMID:24716628

Update on the pathogenesis of Scleroderma: focus on circulating progenitor cells

PubMed Central

Brunasso, Alexandra Maria Giovanna; Massone, Cesare

2016-01-01

In systemic sclerosis (SSc), the development of fibrosis seems to be a consequence of the initial ischemic process related to an endothelial injury. The initial trigger event in SSc is still unknown, but circulating progenitor cells (CPCs) might play a key role. Such cells have the ability to traffic into injury sites, exhibiting inflammatory features of macrophages, tissue remodeling properties of fibroblasts, and vasculogenesis functions of endothelial cells. The different subsets of CPCs described thus far in SSc arise from a pool of circulating monocyte precursors (CD14 + cells) and probably correspond to a different degree of differentiation of a single cell of origin. Several subsets of CPCs have been described in patients with SSc, all have a monocytic origin but may or may not express CD14, and all of these cells have the ability to give origin to endothelial cells, or collagen (Col)-producing cells, or both. We were able to identify six subsets of CPCs: pluripotent stem cells (CD14 +, CD45 +, and CD34 +), monocyte-derived multipotential cells (MOMCs) or monocyte-derived mesenchymal progenitors (CD14 +, CD45 +, CD34 +, Col I +, CD11b +, CD68 +, CD105 +, and VEGFR1 +), early endothelial progenitor cells (EPCs) or monocytic pro-angiogenic hematopoietic cells or circulating hematopoietic cells (CD14 +, CD45 +, CD34 low/−, VEGFR2 +/−, CXCR4 +, c-kit +, and DC117 +), late EPCs (CD14 −, CD133 +, VEGFR2 +, CD144 + [VE-cadherin +], and CD146 +), fibroblast-like cells (FLCs)/circulating Col-producing monocytes (CD14 +, CD45 +, CD34 +/−, and Col I +), and fibrocytes (CD14 −, CD45 +, CD34 +, Col I +, and CXCR4 +). It has been demonstrated that circulating CD14 + monocytes with an activated phenotype are increased in patients with SSc when compared with normal subjects. CD14 +, CD34 +, and Col I + spindle-shaped cells have been found in increased numbers in lungs of SSc patients with interstitial lung disease. Elevated blood amounts of early EPCs have been found in patients with SSc by different groups of researchers and such levels correlate directly with the interstitial lung involvement. The prevalence of hematopoietic markers expressed by CPCs that migrate from blood into injury sites in SSc differs and changes according to the degree of differentiation. CXCR4 is the most commonly expressed marker, followed by CD34 and CD45 at an end stage of differentiation. Such difference also indicates a continuous process of cell differentiation that might relate to the SSc clinical phenotype (degree of fibrosis and vascular involvement). A deeper understanding of the role of each subtype of CPCs in the development of the disease will help us to better classify patients in order to offer them targeted approaches in the future. PMID:27158466

Oral nanotherapeutics: Redox nanoparticles attenuate ultraviolet B radiation-induced skin inflammatory disorders in Kud:Hr- hairless mice.

PubMed

Feliciano, Chitho P; Nagasaki, Yukio

2017-10-01

The active participation of an anti-inflammatory drug in the biological pathways of inflammation is crucial for the achievement of beneficial and therapeutic effects. This study demonstrated the development of redox nanoparticles that can circulate in the blood at significantly high levels, thus increasing their efficacy as an oral treatment against the deleterious effects of reactive oxygen species (ROS) in an in vivo inflammatory skin model. To confirm the blood bioavailability of the nanoparticles, mice were injected with the nanoparticles solution (RNP N ) via oral gavage. Using electron spin resonance and radioactive labeling techniques, the blood circulation of the redox polymer that forms the nanoparticles was confirmed 24 h after oral administration. This contrasted with its low molecular weight counterpart (NH 2 -TEMPO), which peaked 15 min post injection and was found to be cleared rapidly within minutes after the peak. We then tested its efficacy in the inflammatory skin model. Kud:Hr-hairless mice were irradiated with UVB (302 nm) to induce skin damage and inflammation. Throughout the entire period of UVB irradiation, RNP N was administered to mice by free drinking. NH 2 -TEMPO was used as the control. The results showed that oral supplementation of RNP N significantly improved the therapeutic effects of the core nitroxide radical compared with its low molecular weight counterpart. Furthermore, RNP N significantly reduced UVB-induced skin aging, epidermal thickening, edema, erythema, skin lesions, and various pathological skin inflammatory disorders in vivo. From the obtained data, we concluded that the use of long-circulating redox nanoparticles (RNP N ) provided an effective treatment against the damaging effects of excessive ROS in the body. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early Detection of NSCLC Using Stromal Markers in Peripheral Blood

DTIC Science & Technology

2017-11-01

transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating myeloid cells may provide us unique...signature, which may be useful for early lung cancer diagnosis. The specific aims are: Aim 1. To identify a NSCLC- dependent transcriptomic signature in...circulating myeloid cells are transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating

Prostate Cancer Detection by Molecular Urinalysis

DTIC Science & Technology

2008-04-01

proteins.13 We did not specifically assess whether the urinary endoglin we detected was a result of circulating and filtered endoglin or a result of...a marker of pan-endothelial damage and angiogenesis, it is unlikely that circulating endoglin levels would be significantly affected by localized... circulating endoglin is 33 15 increased in metastatic disease states.8,10, 11 Presumably, the angiogenic cascade necessary for metastasis is

The dual anti-inflammatory and antioxidant activities of natural honey promote cell proliferation and neural regeneration in a rat model of colitis.

PubMed

Nooh, Hanaa Z; Nour-Eldien, Nermeen M

2016-07-01

A decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of ulcerative colitis (UC). Recent evidence has suggested a role of honey in reducing colitis-induced inflammatory and oxidative stress markers. In this study, we examined whether the anti-inflammatory and anti-oxidative properties of honey have a beneficial effect on the enteric innervation and cellular proliferation of UC in rat. The colitis was induced in rats by dextran sodium sulphate (DSS). The effect of natural honey on induced colitis was assessed by the following parameters in colonic samples: tissue injury, inflammatory infiltration, interleukin-1β and -6, superoxide dismutase and reduced glutathione. In addition, the expression of tumour necrosis factor-α, inducible NO synthase, caspase-3, CD34, Ki67, S100, c-kit, and neuron-specific enolase were examined by immunohistochemistry. Compared to the DSS-induced colitis group, the honey-treated group had significantly improved macroscopic and microscopic scores and exhibited the down-regulation of oxidative, inflammatory, and apoptotic markers. In addition, up-regulation of intrinsic muscular innervation and epithelial cellular proliferation markers was detected. These results provide new insight into the beneficial role of natural honey in the treatment of DSS-induced colitis via the inhibition of colonic motor dysfunction and the inflammatory-oxidative-apoptotic cascade. In addition, the role of honey in epithelial regeneration was clarified. Copyright © 2016 Elsevier GmbH. All rights reserved.

The Lack of Utility of Circulating Biomarkers of Inflammation and Endothelial Dysfunction for Type 2 Diabetes Risk Prediction Among Postmenopausal Women

PubMed Central

Chao, Chun; Song, Yiqing; Cook, Nancy; Tseng, Chi-Hong; Manson, JoAnn E.; Eaton, Charles; Margolis, Karen L.; Rodriguez, Beatriz; Phillips, Lawrence S.; Tinker, Lesley F.; Liu, Simin

2011-01-01

Background Recent studies have linked plasma markers of inflammation and endothelial dysfunction to type 2 diabetes mellitus (DM) development. However, the utility of these novel biomarkers for type 2 DM risk prediction remains uncertain. Methods The Women’s Health Initiative Observational Study (WHIOS), a prospective cohort, and a nested case-control study within the WHIOS of 1584 incident type 2 DM cases and 2198 matched controls were used to evaluate the utility of plasma markers of inflammation and endothelial dysfunction for type 2 DM risk prediction. Between September 1994 and December 1998, 93 676 women aged 50 to 79 years were enrolled in the WHIOS. Fasting plasma levels of glucose, insulin, white blood cells, tumor necrosis factor receptor 2, interleukin 6, high-sensitivity C-reactive protein, E-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were measured using blood samples collected at baseline. A series of prediction models including traditional risk factors and novel plasma markers were evaluated on the basis of global model fit, model discrimination, net reclassification improvement, and positive and negative predictive values. Results Although white blood cell count and levels of interleukin 6, high-sensitivity C-reactive protein, and soluble intercellular adhesion molecule 1 significantly enhanced model fit, none of the inflammatory and endothelial dysfunction markers improved the ability of model discrimination (area under the receiver operating characteristic curve, 0.93 vs 0.93), net reclassification, or predictive values (positive, 0.22 vs 0.24; negative, 0.99 vs 0.99 [using 15% 6-year type 2 DM risk as the cutoff]) compared with traditional risk factors. Similar results were obtained in ethnic-specific analyses. Conclusion Beyond traditional risk factors, measurement of plasma markers of systemic inflammation and endothelial dysfunction contribute relatively little additional value in clinical type 2 DM risk prediction in a multiethnic cohort of postmenopausal women. PMID:20876407

Stressed lungs: unveiling the role of circulating stress ...

EPA Pesticide Factsheets

Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction with lung lining components causing local oxidative changes, which then leads to cell damage and recruitment of inflammatory cells. It is postulated that the spillover of reactive intermediates and pro-inflammatory molecules from lung to systemic circulation mediates extra-pulmonary effects. However, recent work from our laboratory supports an alternative hypothesis that circulating stress hormones, such as epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects. We have shown in rats and humans that ozone increases the levels of circulating stress hormones through activation of the hypothalamus- pituitary-adrenal (HPA) axis before any measurable effects are observed in the lung. The surgical removal of adrenals diminishes circulating stress hormones and at the same time, the pulmonary effects of ozone suggesting a significant contribution of these hormones in ozone-induced lung injury and inflammation. While ozone effects in the lung have been extensively studied, the contribution of central nervous system -mediated hormonal stress response has not been examined. In order to understand the signaling pathways that might be involved in ozone-induced lun

Association between a Healthy Lifestyle Score and Inflammatory Markers among Puerto Rican adults

PubMed Central

Sotos-Prieto, M; Bhupathiraju, SN; Falcon, LM; Gao, X; Tucker, KL; Mattei, J

2016-01-01

Background and Aims The relationship between multiple lifestyle components analyzed in combination and inflammation remains understudied. We aimed to assess the association between a Healthy Lifestyle Score (HLS) that includes adherence to five behavioral components (diet, physical activity and sedentary behaviors, smoking, social support and network, and sleep) and inflammatory markers, as well as the role of the HLS in inflammation among individuals with cardiometabolic conditions, in Puerto Rican adults. Methods and Results In a cross-sectional study of 842 Puerto Ricans adults (aged 45–75 y) living in Boston, MA, the HLS (range=0–190; maximum indicative of healthiest adherence) was analyzed for association with three inflammatory markers: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). In multivariable-adjusted models, the HLS was inversely associated with IL-6 (β±SE =−0.55 ± 0.13; P<0.001) and TNF-α (−0.39 ± 0.13; P=0.004). The dietary and smoking components were associated with both inflammatory markers independently of the other HLS components. Significant inverse associations were observed for each 20-unit increase in HLS and IL-6 and TNF-α for participants with hypertension (n=600; β±SE = −0.58 ± 0.16; −0.46 ± 0.16, respectively) and with overweight/obesity (n=743; β±SE = −0.59 ± 0.13; −0.50 ± 0.14, respectively), but not for those with diabetes (n=187) or heart disease (n=192). The HLS was not associated with CRP, after adjustment for potential confounders. Conclusion Higher adherence to multiple lifestyle behaviors was associated with lower concentrations of inflammatory markers. Because low-grade inflammation may precede chronic diseases, following an overall healthy lifestyle may help lower risk of these diseases. PMID:26838054

Association between a Healthy Lifestyle Score and inflammatory markers among Puerto Rican adults.

PubMed

Sotos-Prieto, M; Bhupathiraju, S N; Falcon, L M; Gao, X; Tucker, K L; Mattei, J

2016-03-01

The relationship between multiple lifestyle components analyzed in combination and inflammation remains understudied. We aimed to assess the association between a Healthy Lifestyle Score (HLS) that includes adherence to five behavioral components (diet, physical activity and sedentary behaviors, smoking, social support and network, and sleep) and inflammatory markers, as well as the role of the HLS in inflammation among individuals with cardiometabolic conditions, in Puerto Rican adults. In a cross-sectional study of 842 Puerto Ricans adults (aged 45-75 y) living in Boston, MA, the HLS (range = 0-190; maximum indicative of healthiest adherence) was analyzed for association with three inflammatory markers: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). In multivariable-adjusted models, the HLS was inversely associated with IL-6 (β ± SE = -0.55 ± 0.13; P < 0.001) and TNF-α (-0.39 ± 0.13; P = 0.004). The dietary and smoking components were associated with both inflammatory markers independently of the other HLS components. Significant inverse associations were observed for each 20-unit increase in HLS and IL-6 and TNF-α for participants with hypertension (n = 600; β ± SE = -0.58 ± 0.16; -0.46 ± 0.16, respectively) and with overweight/obesity (n = 743; β ± SE = -0.59 ± 0.13; -0.50 ± 0.14, respectively), but not for those with diabetes (n = 187) or heart disease (n = 192). The HLS was not associated with CRP, after adjustment for potential confounders. Higher adherence to multiple lifestyle behaviors was associated with lower concentrations of inflammatory markers. Because low-grade inflammation may precede chronic diseases, following an overall healthy lifestyle may help lower risk of these diseases. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

The performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis.

PubMed

Michail, Marios; Jude, Edward; Liaskos, Christos; Karamagiolis, Spyridon; Makrilakis, Konstantinos; Dimitroulis, Dimitrios; Michail, Othon; Tentolouris, Nicholas

2013-06-01

Serum inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), and procalcitonin (PCT), have been used for the diagnosis of foot infections in patients with diabetes. However, little is known about their changes during treatment of patients with foot infections. The aim of this prospective study was to examine the performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis. A total of 61 patients (age 63.1 ± 7.0 years, 45 men and 16 women, 7 with type 1 and 54 with type 2 diabetes) with untreated foot infection (34 with soft-tissue infection and 27 with osteomyelitis) were recruited. Diagnosis of osteomyelitis was based on clinical examination and was confirmed by imaging studies (X-ray, scintigraphy, magnetic resonance imaging). Determination of the inflammatory markers was performed at baseline, after 1 week, after 3 weeks, and after 3 months of treatment. At baseline, the values of CRP, ESR, WBC, and PCT were significantly higher in patients with osteomyelitis than in those with soft-tissue infections. The sensitivity and specificity for the diagnosis of osteomyelitis of CRP (cutoff value >14 mg/L) were 0.85 and 0.83, of ESR (cutoff value >67 mm/h) 0.84 and 0.75, of WBC (cutoff value >14 × 10(9)/L) 0.75 and 0.79, and of PCT (cutoff value >0.30 ng/mL) 0.81 and 0.71, respectively. All values declined after initiation of treatment with antibiotics; the WBC, CRP, and PCT values returned to near-normal levels at day 7, whereas the values of ESR remained high until month 3 only in patients with bone infection. From the inflammatory markers, ESR is recommended to be used for the follow-up of patients with osteomyelitis.

Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+ macrophages, but not their tolerogenic CD11c-CCR2-CX3CR1- counterparts, are expanded in inflammatory bowel disease.

PubMed

Bernardo, D; Marin, A C; Fernández-Tomé, S; Montalban-Arques, A; Carrasco, A; Tristán, E; Ortega-Moreno, L; Mora-Gutiérrez, I; Díaz-Guerra, A; Caminero-Fernández, R; Miranda, P; Casals, F; Caldas, M; Jiménez, M; Casabona, S; De la Morena, F; Esteve, M; Santander, C; Chaparro, M; Gisbert, J P

2018-05-09

Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45 + HLA-DR + CD14 + CD64 + ) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11c high CCR2 + CX3CR1 + cells, a phenotype also shared by circulating CD14 + monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c - CCR2 - CX3CR1 - phenotype. CD11c high monocyte-like cells produced IL-1β, both in resting conditions and after LPS stimulation, while CD11c - Mϕ-like cells produced IL-10. CD11c high pro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c - Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14 + monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11c high CCR2 + CX3CR1 + ) into tolerogenic tissue-resident (CD11c - CCR2 - CX3CR1 - ) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c - Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11c high monocyte-like cells.

PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model.

PubMed

Anitua, E; Muruzabal, F; de la Fuente, M; Riestra, A; Merayo-Lloves, J; Orive, G

2016-10-01

Ocular graft versus host disease (oGVHD) is part of a systemic inflammatory disease that usually affects ocular surface tissues manifesting as a dry eye syndrome. Current treatments provide unsatisfactory results. Blood-derived products, like plasma rich in growth factors (PRGF) emerge as a potential therapy for this disease. The purpose of this study was to evaluate the tissue regeneration and anti-inflammatory capability of PRGF, an autologous platelet enriched plasma eye-drop, compared to autologous serum (AS) obtained from oGVHD patients on ocular surface cells cultured in a pro-inflammatory environment. PRGF and AS were obtained from four GVHD patients. Cell proliferation and inflammation markers, intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2), were measured in corneal and conjunctival fibroblastic cells cultured under pro-inflammatory conditions and after treatment with PRGF or AS eye drops. Moreover, cell proliferation increased after treatment with PRGF and AS, though this enhancement in the case of keratocytes was significantly higher with PRGF. PRGF eye drops showed a significant reduction of both inflammatory markers with respect to the initial inflammatory situation and to the AS treatment. Our results concluded that PRGF exerts more potent regenerative and anti-inflammatory effects than autologous serum on ocular surface fibroblasts treated with pro-inflammatory IL-1β and TNFα. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional Biomarkers of Depression: Diagnosis, Treatment, and Pathophysiology

PubMed Central

Schmidt, Heath D; Shelton, Richard C; Duman, Ronald S

2011-01-01

Major depressive disorder (MDD) is a heterogeneous illness for which there are currently no effective methods to objectively assess severity, endophenotypes, or response to treatment. Increasing evidence suggests that circulating levels of peripheral/serum growth factors and cytokines are altered in patients with MDD, and that antidepressant treatments reverse or normalize these effects. Furthermore, there is a large body of literature demonstrating that MDD is associated with changes in endocrine and metabolic factors. Here we provide a brief overview of the evidence that peripheral growth factors, pro-inflammatory cytokines, endocrine factors, and metabolic markers contribute to the pathophysiology of MDD and antidepressant response. Recent preclinical studies demonstrating that peripheral growth factors and cytokines influence brain function and behavior are also discussed along with their implications for diagnosing and treating patients with MDD. Together, these studies highlight the need to develop a biomarker panel for depression that aims to profile diverse peripheral factors that together provide a biological signature of MDD subtypes as well as treatment response. PMID:21814182

Assessment of Salivary Adipokines Resistin, Visfatin, and Ghrelin as Type 2 Diabetes Mellitus Biomarkers

PubMed Central

Meadows, Melinda L.; Maxwell, Lisa

2018-01-01

Type 2 diabetes mellitus (T2DM) is emerging as a metabolic epidemic worldwide. Pathologically, dysregulation of many biological pathways precedes hyperglycemia and the clinical diagnosis of T2DM. Changing trajectories along the process of T2DM development necessitates frequent measurement of biomarkers for early identification of at-risk individuals and successful prevention. Increase in circulating inflammatory adipokines has been suggested as predictive of T2DM. Human saliva is an easily accessible biospecimen amenable for painless frequent collection and possesses nearly 50% of serum proteome. In this study, we measured the adipokines resistin, visfatin, TNF-α, and ghrelin as markers for T2DM in unstimulated whole saliva (UWS) using specific assay kits. Resistin and visfatin concentrations were significantly higher in T2DM saliva. Although the concentration of acylated or unacylated ghrelin was lower in diabetic saliva, the decrease was not significant. Since resistin and visfatin are biomarkers integral to T2DM pathology, their salivary assessments may receive clinical acceptance. PMID:29487749

Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA.

PubMed

Hirsch, Mauro Mozael; Deckmann, Iohanna; Fontes-Dutra, Mellanie; Bauer-Negrini, Guilherme; Della-Flora Nunes, Gustavo; Nunes, Walquiria; Rabelo, Bruna; Riesgo, Rudimar; Margis, Rogerio; Bambini-Junior, Victorio; Gottfried, Carmem

2018-05-01

Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication and language, and restricted repertoire of activities and interests. The etiology of ASD remains unknown and no clinical markers for diagnosis were identified. Environmental factors, including prenatal exposure to valproic acid (VPA), may contribute to increased risk of developing ASD. MicroRNA (miRNA) are small noncoding RNA that regulate gene expression and are frequently linked to biological processes affected in neurodevelopmental disorders. In this work, we analyzed the effects of resveratrol (an antioxidant and anti-inflammatory molecule) on behavioral alterations of the VPA model of autism, as well as the levels of circulating miRNA. We also evaluated the same set of miRNA in autistic patients. Rats of the VPA model of autism showed reduced total reciprocal social interaction, prevented by prenatal treatment with resveratrol (RSV). The levels of miR134-5p and miR138-5p increased in autistic patients. Interestingly, miR134-5p is also upregulated in animals of the VPA model, which is prevented by RSV. In conclusion, our findings revealed important preventive actions of RSV in the VPA model, ranging from behavior to molecular alterations. Further evaluation of preventive mechanisms of RSV can shed light in important biomarkers and etiological triggers of ASD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dietary Advanced Glycation End Products and Cardiometabolic Risk.

PubMed

Luévano-Contreras, Claudia; Gómez-Ojeda, Armando; Macías-Cervantes, Maciste Habacuc; Garay-Sevilla, Ma Eugenia

2017-08-01

This report analyzes emerging evidence about the role of dietary advanced glycation end products (AGEs) as a cardiometabolic risk factor. Two important aspects are discussed: First, the modulation of AGE load by dietary AGEs; second, if the evidence of clinical and observational studies is enough to make dietary recommendations towards lowering AGE intake. Clinical studies in subjects with diabetes mellitus have shown that high intake of dietary AGEs increases inflammation markers, oxidative stress, and could impair endothelial function. In subjects at risk for cardiometabolic diseases (with overweight, obesity, or prediabetes), dietary AGE restriction decreases some inflammatory molecules and improves insulin sensitivity. However, studies in healthy subjects are limited, and not all of the studies have shown a decrease in circulating AGEs. Therefore, it is still unclear if dietary AGEs represent a health concern for people potentially at risk for cardiometabolic diseases. The evidence shows that dietary AGEs are bioavailable and absorbed, and the rate of excretion depends on dietary intake. The metabolic fate of most dietary AGEs remains unknown. Regardless, most studies have shown that by diminishing AGE intake, circulating levels will also decrease. Thus, dietary AGEs can modulate the AGE load at least in patients with DM, overweight, or obesity. Studies with specific clinical outcomes and large-scale observational studies are needed for a better risk assessment of dietary AGEs and to establish dietary recommendations accordingly.

Against the Role of Inflammatory Markers in Renal Cell Carcinoma Prognosis: The Missing Link Between Evidence of Association and Clinical Applicability.

PubMed

Larcher, Alessandro; Dell'Oglio, Paolo; Salonia, Andrea; Capitanio, Umberto

2016-10-01

Although an association between inflammatory markers (IMs) and renal cell carcinoma (RCC) prognosis has been proven, how to translate such information into treatment strategy has not been determined. The strongest argument against the use of IMs in the management of patients diagnosed with RCC is the missing link between evidence of association and clinical applicability. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Expression of miR-155, miR-146a, and miR-326 in T1D patients from Chile: relationship with autoimmunity and inflammatory markers.

PubMed

García-Díaz, Diego F; Pizarro, Carolina; Camacho-Guillén, Patricia; Codner, Ethel; Soto, Néstor; Pérez-Bravo, Francisco

2018-02-01

Objective The aim of this research was to analyze the expression profile of miR-155, miR-146a, and miR-326 in peripheral blood mononuclear cells (PBMC) of 47 patients with type 1 diabetes mellitus (T1D) and 39 control subjects, as well as the possible association with autoimmune or inflammatory markers. Subjects and methods Expression profile of miRs by means of qPCR using TaqMan probes. Autoantibodies and inflammatory markers by ELISA. Statistical analysis using bivariate correlation. Results The analysis of the results shows an increase in the expression of miR-155 in T1D patients in basal conditions compared to the controls (p < 0.001) and a decreased expression level of miR-326 (p < 0.01) and miR-146a (p < 0.05) compared T1D patients to the controls. miR-155 was the only miRs associated with autoinmmunity (ZnT8) and inflammatory status (vCAM). Conclusion Our data show a possible role of miR-155 related to autoimmunity and inflammation in Chilean patients with T1D.

Diabetic Foot Syndrome as a Possible Cardiovascular Marker in Diabetic Patients

PubMed Central

Tuttolomondo, Antonino; Maida, Carlo; Pinto, Antonio

2015-01-01

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality; in fact, some authors showed a higher prevalence of major, previous and new-onset, cardiovascular, and cerebrovascular events in diabetic patients with foot ulcers than in those without these complications. This is consistent with the fact that in diabetes there is a complex interplay of several variables with inflammatory metabolic disorders and their effect on the cardiovascular system that could explain previous reports of high morbidity and mortality rates in diabetic patients with amputations. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects confirmed the pathogenetic issue of the “adipovascular” axis that may contribute to cardiovascular risk in patients with type 2 diabetes. In patients with diabetic foot, this “adipovascular axis” expression in lower plasma levels of adiponectin and higher plasma levels of IL-6 could be linked to foot ulcers pathogenesis by microvascular and inflammatory mechanisms. The purpose of this review is to focus on the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients. PMID:25883983

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

PubMed Central

Kim, Deog Kyeom; Cho, Michael H.; Hersh, Craig P.; Lomas, David A.; Miller, Bruce E.; Kong, Xiangyang; Bakke, Per; Gulsvik, Amund; Agustí, Alvar; Wouters, Emiel; Celli, Bartolome; Coxson, Harvey; Vestbo, Jørgen; MacNee, William; Yates, Julie C.; Rennard, Stephen; Litonjua, Augusto; Qiu, Weiliang; Beaty, Terri H.; Crapo, James D.; Riley, John H.; Tal-Singer, Ruth

2012-01-01

Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10−8), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009–0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001–0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:23144326

Results of the 4th scientific workshop of the ECCO (Group II): markers of intestinal fibrosis in inflammatory bowel disease.

PubMed

Rieder, Florian; de Bruyn, Jessica R; Pham, Bao Tung; Katsanos, Konstantinos; Annese, Vito; Higgins, Peter D R; Magro, Fernando; Dotan, Iris

2014-10-01

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on intestinal fibrosis in inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms and markers of intestinal fibrosis as well as to suggest new therapeutic targets to prevent or treat fibrosis. The results of this workshop are presented in three separate manuscripts. This section describes markers of fibrosis in IBD, identifies unanswered questions in the field and provides a framework for future studies addressing the unmet needs in the field of intestinal fibrosis. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Sepsis-induced activation of endogenous GLP-1 system is enhanced in type 2 diabetes.

PubMed

Perl, Sivan H; Bloch, Olga; Zelnic-Yuval, Dana; Love, Itamar; Mendel-Cohen, Lior; Flor, Hadar; Rapoport, Micha J

2018-05-01

High levels of circulating GLP-1 are associated with severity of sepsis in critically ill nondiabetic patients. Whether patients with type 2 diabetes (T2D) display different activation of the endogenous GLP-1 system during sepsis and whether it is affected by diabetes-related metabolic parameters are not known. Serum levels of GLP-1 (total and active forms) and its inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2 to 4 days in 37 sepsis patients with (n = 13) and without T2D (n = 24) and compared to normal healthy controls (n = 25). Correlations between GLP-1 system activation and clinical, inflammatory, and diabetes-related metabolic parameters were performed. A 5-fold (P < .001) and 2-fold (P < .05) increase in active and total GLP-1 levels, respectively, were found on admission as compared to controls. At 2 to 4 days from admission, the level of active GLP-1 forms in surviving patients were decreased significantly (P < .005), and positively correlated with inflammatory marker CRP (r = 0.33, P = .05). T2D survivors displayed a similar but more enhanced pattern of GLP-1 response than nondiabetic survivors. Nonsurvivors demonstrate an early extreme increase of both total and active GLP-1 forms, 9.5-fold and 5-fold, respectively (P < .05). The initial and late levels of circulating GLP-1 inhibitory enzyme sDPP-4 were twice lower in all studied groups (P < .001), compared with healthy controls. Taken together, these data indicate that endogenous GLP-1 system is activated during sepsis. Patients with T2D display an enhanced and prolonged activation as compared to nondiabetic patients. Extreme early increased GLP-1 levels during sepsis indicate poor prognosis. Copyright © 2018 John Wiley & Sons, Ltd.

Label-free isolation of circulating tumor cells in microfluidic devices: Current research and perspectives.

PubMed

Cima, Igor; Wen Yee, Chay; Iliescu, Florina S; Phyo, Wai Min; Lim, Kiat Hon; Iliescu, Ciprian; Tan, Min Han

2013-01-01

This review will cover the recent advances in label-free approaches to isolate and manipulate circulating tumor cells (CTCs). In essence, label-free approaches do not rely on antibodies or biological markers for labeling the cells of interest, but enrich them using the differential physical properties intrinsic to cancer and blood cells. We will discuss technologies that isolate cells based on their biomechanical and electrical properties. Label-free approaches to analyze CTCs have been recently invoked as a valid alternative to "marker-based" techniques, because classical epithelial and tumor markers are lost on some CTC populations and there is no comprehensive phenotypic definition for CTCs. We will highlight the advantages and drawbacks of these technologies and the status on their implementation in the clinics.

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

PubMed

Wagner, En-Young N; Wagner, Jan T; Glaus, Jennifer; Vandeleur, Caroline L; Castelao, Enrique; Strippoli, Marie-Pierre F; Vollenweider, Peter; Preisig, Martin; von Känel, Roland

2015-01-01

Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

Early Detection of NSCLC Using Stromal Markers in Peripheral Blood

DTIC Science & Technology

2016-09-01

circulating myeloid cells, flow cytometry, RNA -sequencing, expression profiling. 3. ACCOMPLISHMENTS:  What were the major goals of the project...Subtask 2: Flow cytometry sorting of circulating myeloid cells. Subtask 3: RNA -Sequencing Subtask 4: RNA -seq data analysis Subtask 5: Feasible RT-PCR...accomplished the patient recruitment, flow cytometry sorting of circulating myeloid cells, RNA -sequencing of the samples. During the RNA - seq data analysis, we

Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study.

PubMed

Naito, Toshio; Torikai, Keito; Mizooka, Masafumi; Mitsumoto, Fujiko; Kanazawa, Kenji; Ohno, Shiro; Morita, Hiroyuki; Ukimura, Akira; Mishima, Nobuhiko; Otsuka, Fumio; Ohyama, Yoshio; Nara, Noriko; Murakami, Kazunari; Mashiba, Kouichi; Akazawa, Kenichiro; Yamamoto, Koji; Tanei, Mika; Yamanouchi, Masashi; Senda, Shoichi; Tazuma, Susumu; Hayashi, Jun

2015-01-01

Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats.

PubMed

Famurewa, Ademola C; Aja, Patrick M; Maduagwuna, Ekenechukwu K; Ekeleme-Egedigwe, Chima A; Ufebe, Odomero G; Azubuike-Osu, Sharon O

2017-12-01

Methotrexate (MTX) is an efficacious anticancer agent constrained in clinical use due to its toxicity on non-targeted tissue, a considerable source of worry to clinicians. Because the toxicity is associated with oxidative stress and inflammation, the study explored antioxidant and anti-inflammatory effect of virgin coconut oil (VCO) supplementation in nephrotoxicity induced by MTX in rats. Rats were randomized into 4 groups (n=6) as follows: Control group; MTX group injected with single dose of MTX (20mg/kg, ip) on day 14; VCO (5%)+MTX and VCO (15%)+MTX groups were pre-treated with VCO diet and injected with single dose of MTX (20mg/kg, ip) on day 14. After 3 days of MTX injection, serum kidney markers, renal activities of antioxidant enzymes and glutathione (GSH) content were determined. Lipid peroxidation level and inflammatory markers- interleukin-6 (IL-6), nitric oxide (NO) and C-reactive protein (CRP) were estimated in kidney. Histopathological alterations were examined for kidney damage. MTX nephrotoxicity was evidenced by markedly elevated serum renal markers along with significant decreases in renal GSH and activities of antioxidant enzymes confirmed by histopathology. Lipid peroxidation level, IL-6, NO and CRP markedly increased compared to control. VCO supplementation prior to MTX injection attenuated MTX-induced oxidative nephrotoxicity via prominent increases in GSH and antioxidant enzyme activities in a dose-dependent manner. The renal inflammatory markers and MDA depleted considerably compared to MTX control group. Histopathological alterations were mitigated to confirm the biochemical indices. VCO supplementation demonstrates nephroprotective activity by attenuating MTX oxidative nephrotoxicity via antioxidant and anti-inflammatory activities in kidney. Our results suggested that VCO may benefit cancer patients on MTX chemotherapy against kidney injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Expression of pericardial fluid T-cells and related inflammatory cytokines in patients with chronic heart failure.

PubMed

Iskandar, Reinard; Liu, Shengchen; Xiang, Fei; Chen, Wen; Li, Liangpeng; Qin, Wei; Huang, Fuhua; Chen, Xin

2017-05-01

Pericardial fluid, as a biochemical indicator of heart status, directly indicates pathological alteration to the heart. The accumulation of pericardial fluid can be attributed to an underlying systemic or local inflammatory process. However, the pericardial fluid expression of cellular surface markers, as well as several cytokines in chronic heart failure (CHF), remain unclear. In order to evaluate these issues further the pericardial fluid expression of several cytokines and the surface expression of activity markers between CHF patients and non-heart failure (NHF) patients were analyzed. The pericardial fluid expression of cytokines was measured by immunofluorescence and biomarker of plasma N-terminal propeptide of B-type natriuretic peptide (NT-proBNP), while pericardial fluid levels of soluble glycoprotein 130 (sgp130) were analyzed by ELISA in 50 CHF and 24 NHF patients. In addition, the surface expression of activation markers for T-cells was measured by immunohistochemistry. Patients with CHF demonstrated increased levels of plasma NT-proBNP and pericardial fluid sgp130. Surface expression of cellular activation markers CD25 and Foxp3 in the pericardial fluid was increased in patients with CHF. Moreover, the pro- and anti-inflammatory cytokines interferon (IFN)-γ, interleukin (IL)-6 and IL-10 in patients with CHF also demonstrated an increased expression within its pericardial fluid. In addition, there was infiltration of inflammatory cells and enhanced expression of inflammatory cytokines in the pericardial fluid of patients with CHF, which may reflect T cell activation, suggesting that systemic inflammation is important in the progression of CHF. This evidence could indicate a possible novel target for future therapeutics and prevention of CHF.

Affective and inflammatory responses among orchestra musicians in performance situation.

PubMed

Pilger, Alexander; Haslacher, Helmuth; Ponocny-Seliger, Elisabeth; Perkmann, Thomas; Böhm, Karl; Budinsky, Alexandra; Girard, Angelika; Klien, Katharina; Jordakieva, Galateja; Pezawas, Lukas; Wagner, Oswald; Godnic-Cvar, Jasminka; Winker, Robert

2014-03-01

A number of studies have shown that mental challenge under controlled experimental conditions is associated with elevations in inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). However, relatively little work has been done on the effects of 'naturalistic' stressors on acute changes in inflammatory markers. The present study examined whether perceived arousal, valence and dominance in musicians are associated with pro-inflammatory and oxidative responses to a concert situation. Blood and salivary samples obtained from 48 members of a symphony orchestra on the day of rehearsal (i.e., control situation) and on the following day of premiere concert (i.e., test situation) were used to determine changes in salivary cortisol, pro-inflammatory markers (plasma myeloperoxidase, serum CRP, plasma IL-6), oxidative stress markers (paraoxonase1 activity and malondialdehyde), and homocysteine, a risk factor for vascular disease. Results of regression analyses showed a significant trend to increased myeloperoxidase (MPO) response in individuals with low valence score. Both affective states, valence and arousal, were identified as significant predictors of cortisol response during concert. In addition, control levels of plasma malondialdehyde were positively correlated with differences in IL-6 levels between premiere and rehearsal (r=.38, p=.012), pointing to higher oxidative stress in individuals with pronounced IL-6 response. Our results indicate that stress of public performance leads to increased concentrations of plasma MPO (20%), IL-6 (27%) and salivary cortisol (44%) in musicians. The decreasing effect of pleasantness on the MPO response was highly pronounced in non-smokers (r=-.60, p<.001), suggesting a significant role of emotional valence in stress-induced secretion of MPO. Additional studies are needed to assess the generalizability of these findings to other 'naturalistic' stress situations. Copyright © 2013 Elsevier Inc. All rights reserved.

Strain-specific probiotic (microbial cell preparation) and omega-3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial.

PubMed

Golkhalkhali, Babak; Rajandram, Retnagowri; Paliany, Audra Shaleena; Ho, Gwo Fuang; Wan Ishak, Wan Zamaniah; Johari, Che Shafini; Chin, Kin Fah

2018-06-01

Colorectal cancer patients on chemotherapy usually have elevated levels of inflammatory markers and experience numerous side effects from chemotherapy thereby leading to poor quality of life. Omega-3 fatty acid and microbial cell preparation (MCP) have been known to provide significant benefits in patients on chemotherapy. The aim of this study was to determine the effect of supplementation of omega-3 fatty acid and MCP in quality of life, chemotherapy side effects and inflammatory markers in colorectal cancer patients on chemotherapy. A double-blind randomized study was carried out with 140 colorectal cancer patients on chemotherapy. Subjects were separated into two groups to receive either placebo or MCP [30 billion colony-forming unit (CFUs) per sachet] at a dose of two sachets daily for 4 weeks, and omega-3 fatty acid at a dose of 2 g daily for 8 weeks. Outcomes measured were quality of life, side effects of chemotherapy and levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein. The supplementation with MCP and omega-3 fatty acid improved the overall quality of life and alleviated certain side effects of chemotherapy. The supplementation with MCP and omega-3 fatty acid also managed to reduce the level of IL-6 (P = 0.002). There was a significant rise in the placebo group's serum TNF-α (P = 0.048) and IL-6 (P = 0.004). The combined supplementation with MCP and omega-3 fatty acid may improve quality of life, reduce certain inflammatory biomarkers and relieve certain side effects of chemotherapy in colorectal patients on chemotherapy. © 2017 John Wiley & Sons Australia, Ltd.

C-reactive protein levels and treatment resistance in schizophrenia-A Danish population-based cohort study.

PubMed

Horsdal, Henriette Thisted; Wimberley, Theresa; Benros, Michael Eriksen; Gasse, Christiane

2017-11-01

Schizophrenia is associated with increased levels of inflammatory markers. However, it remains unclear whether inflammatory markers are associated with treatment-resistant schizophrenia. We conducted a population-based follow-up study among individuals with a first-time schizophrenia diagnosis and a baseline C-reactive protein measurement (a commonly available marker of systemic inflammation) from 2000 to 2012. We defined treatment resistance as the earliest observed instance of either clozapine initiation or hospital admission due to schizophrenia after having received at least 2 prior antipsychotic monotherapy trials of adequate duration. We used adjusted Cox regression analysis to calculate hazard ratios. We identified 390 individuals with a C-reactive protein measurement at first-time schizophrenia diagnosis. A nonsignificant higher median C-reactive protein (4.0 vs. 3.1 mg/L, p = .13) was observed among the 52 (13.3%) treatment-resistant individuals. Increased levels of C-reactive protein (above 3 mg/L) at baseline were not associated with treatment resistance (adjusted hazard ratio = 0.99, 95% confidence interval [0.56, 1.73]). C-reactive protein, as a single inflammatory marker, appears insufficient to detect treatment-resistant schizophrenia. Copyright © 2017 John Wiley & Sons, Ltd.

Severe Alcoholic Pancreatitis-Associated Acute Lung Injury in Veterans: Risks, Mechanisms, Prediction, and Therapeutic Relevance

DTIC Science & Technology

2017-10-01

discovered that one of the controls, who is morbidly obese , diabetic, had a very high number of dead inflammatory cells in circulation. While this is a...very interesting finding, it is more likely that the dead inflammatory cells are coming from the obesity and severe diabetes. Because of this severe

Low tidal volume and high positive end-expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs.

PubMed

Hong, Caron M; Xu, Da-Zhong; Lu, Qi; Cheng, Yunhui; Pisarenko, Vadim; Doucet, Danielle; Brown, Margaret; Aisner, Seena; Zhang, Chunxiang; Deitch, Edwin A; Delphin, Ellise

2010-06-01

Protective mechanical ventilation with low tidal volume (Vt) and low plateau pressure reduces mortality and decreases the length of mechanical ventilation in patients with acute respiratory distress syndrome. Mechanical ventilation that will protect normal lungs during major surgical procedures of long duration may improve postoperative outcomes. We performed an animal study comparing 3 ventilation strategies used in the operating room in normal lungs. We compared the effects on pulmonary mechanics, inflammatory mediators, and lung tissue injury. Female pigs were randomized into 3 groups. Group H-Vt/3 (n = 6) was ventilated with a Vt of 15 mL/kg predicted body weight (PBW)/positive end-expiratory pressure (PEEP) of 3 cm H(2)O, group L-Vt/3 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 3 cm H(2)O, and group L-Vt/10 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 10 cm H(2)O, for 8 hours. Hemodynamics, airway mechanics, arterial blood gases, and inflammatory markers were monitored. Bronchoalveolar lavage (BAL) was analyzed for inflammatory markers and protein concentration. The right lower lobe was assayed for mRNA of specific cytokines. The right lower lobe and right upper lobe were evaluated histologically. In contrast to groups H-Vt/3 and L-Vt/3, group L-Vt/10 exhibited a 6-fold increase in inflammatory mediators in BAL (P < 0.001). Cytokines in BAL were similar in groups H-Vt/3 and L-Vt/3. Group H-Vt/3 had a significantly lower lung injury score than groups L-Vt/3 and L-Vt/10. Comparing intraoperative strategies, ventilation with high PEEP resulted in increased production of inflammatory markers. Low PEEP resulted in lower levels of inflammatory markers. High Vt/low PEEP resulted in less histologic lung injury.

EFFECTS OF TRANSDERMAL TESTOSTERONE TREATMENT ON INFLAMMATORY MARKERS IN ELDERLY MEN

PubMed Central

Maggio, Marcello; Snyder, Peter J.; De Vita, Francesca; Ceda, Gian Paolo; Milaneschi, Yuri; Lauretani, Fulvio; Luci, Michele; Cattabiani, Chiara; Peachey, Helen; Valenti, Giorgio; Cappola, Anne R; Longo, Dan L.; Ferrucci, Luigi

2016-01-01

Objective During the aging process in men testosterone (T) levels progressively fall and inflammatory biomarkers increase. Although a relationship between these two phenomena has been tested in previous clinical trials, there is inconclusive evidence about the potential anti-inflammatory action of T. Methods A total of 108 healthy men >65 years with serum T concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University, and randomized to 60-cm2 T or placebo patch for 36-months. Ninety-six subjects completed the trial. Information and stored serum specimens from this trial were used to test the hypothesis of T inhibitory effect on inflammation. 70 men (42 in the T group) who had banked specimens available for assays of T, C-reactive protein (CRP), Tumor necrosis factor (TNF)-alpha, soluble TNF-alpha receptor-1 (TNFR1), interleukin-6 (IL-6) and soluble IL-6 receptors (sIL6r and sgp130) at multiple time points, were evaluated. Results The mean age ± SD at baseline was 71.8 ± 4.9 years. Testosterone replacement therapy for 36 months did not induce a significant decrease in inflammatory markers. A trend toward a significant increase was observed in the placebo group for TNF-alpha (p=0.03) and sgp130 (p=0.01). Significant differences, in estimated means of TNFR1 (but not of other inflammatory markers), with lower levels in T group, were observed at 36 month-time point. In T-treated subjects we found an almost significant treatment-time interaction term TNFR1 (p=0.02) independent of total body fat content assessed by DXA. No serious adverse effect was observed. Conclusions Transdermal T treatment of older men for 36 months is not associated with significant changes in inflammatory markers. PMID:25100359

Effects of transdermal testosterone treatment on inflammatory markers in elderly males.

PubMed

Maggio, Marcello; Snyder, Peter J; De Vita, Francesca; Ceda, Gian Paolo; Milaneschi, Yuri; Lauretani, Fulvio; Luci, Michele; Cattabiani, Chiara; Peachey, Helen; Valenti, Giorgio; Cappola, Anne R; Longo, Dan L; Ferrucci, Luigi

2014-11-01

During the male aging process, testosterone (T) levels progressively fall and inflammatory biomarkers increase. Although a relationship between these 2 phenomena has been tested in previous clinical trials, there is inconclusive evidence about the potential anti-inflammatory action of T. A total of 108 healthy males >65 years with serum T concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University and randomized to 60-cm2 T or a placebo patch for 36 months. Ninety-six subjects completed the trial. Information and stored serum specimens from this trial were used to test the hypothesis of the inhibitory effect of T on inflammation. We evaluated 70 males (42 in the T group) who had banked specimens from multiple time points available for assays of T, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, soluble TNF-α receptor-1 (TNFR1), interleukin-6 (IL-6), and soluble IL-6 receptors (sIL6r and sgp130). The mean age ± SD at baseline was 71.8 ± 4.9 years. Testosterone replacement therapy for 36 months did not induce significant decreases in inflammatory markers. A trend toward a significant increase was observed in the placebo group for TNF-α (P = .03) and sgp130 (P = .01). Significant differences in estimated means of TNFR1 (but not other inflammatory markers), with lower levels in the T group, were observed at the 36-month time point. In T-treated subjects we found an almost significant treatment x time interaction term TNFR1 (P = .02) independent of total body fat content as assessed by dual energy X-ray absorptiometry (DXA). No serious adverse effect was observed. Transdermal T treatment of older males for 36 months is not associated with significant changes in inflammatory markers.

Comprehensive metabolic profiling of chronic low-grade inflammation among generally healthy individuals.

PubMed

Pietzner, Maik; Kaul, Anne; Henning, Ann-Kristin; Kastenmüller, Gabi; Artati, Anna; Lerch, Markus M; Adamski, Jerzy; Nauck, Matthias; Friedrich, Nele

2017-11-30

Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers. Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis. HsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3'-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83). Comprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders.

Connecting the Dots: Could Microbial Translocation Explain Commonly Reported Symptoms in HIV Disease?

PubMed Central

Wilson, Natalie L.; Vance, David E.; Moneyham, Linda D.; Raper, James L.; Mugavero, Michael J.; Heath, Sonya L.; Kempf, Mirjam-Colette

2017-01-01

Microbial translocation within the context of HIV disease has been described as one of the contributing causes of inflammation and disease progression in HIV infection. HIV-associated symptoms have been related to inflammatory markers and sCD14, a surrogate marker for microbial translocation, suggesting a plausible link between microbial translocation and symptom burden in HIV disease. Similar pathophysiological responses and symptoms have been reported in inflammatory bowel disease. We provide a comprehensive review of microbial translocation, HIV-associated symptoms, and symptoms connected with inflammation. We identify studies showing a relationship among inflammatory markers, sCD14, and symptoms reported in HIV disease. A conceptual framework and rationale to investigate the link between microbial translocation and symptoms is presented. The impact of inflammation on symptoms supports recommendations to reduce inflammation as part of HIV symptom management. Research in reducing microbial translocation-induced inflammation is limited, but needed, to further promote positive health outcomes among HIV-infected patients. PMID:25305025

Connecting the dots: could microbial translocation explain commonly reported symptoms in HIV disease?

PubMed

Wilson, Natalie L; Vance, David E; Moneyham, Linda D; Raper, James L; Mugavero, Michael J; Heath, Sonya L; Kempf, Mirjam-Colette

2014-01-01

Microbial translocation within the context of HIV disease has been described as one of the contributing causes of inflammation and disease progression in HIV infection. HIV-associated symptoms have been related to inflammatory markers and sCD14, a surrogate marker for microbial translocation, suggesting a plausible link between microbial translocation and symptom burden in HIV disease. Similar pathophysiological responses and symptoms have been reported in inflammatory bowel disease. We provide a comprehensive review of microbial translocation, HIV-associated symptoms, and symptoms connected with inflammation. We identify studies showing a relationship among inflammatory markers, sCD14, and symptoms reported in HIV disease. A conceptual framework and rationale to investigate the link between microbial translocation and symptoms is presented. The impact of inflammation on symptoms supports recommendations to reduce inflammation as part of HIV symptom management. Research in reducing microbial translocation-induced inflammation is limited, but needed, to further promote positive health outcomes among HIV-infected patients. Published by Elsevier Inc.

High-intensity interval training improves inflammatory and adipokine profiles in postmenopausal women with metabolic syndrome.

PubMed

Steckling, Flávia Mariel; Farinha, Juliano Boufleur; Figueiredo, Felipe da Cunha; Santos, Daniela Lopes Dos; Bresciani, Guilherme; Kretzmann, Nélson Alexandre; Stefanello, Sílvio Terra; Courtes, Aline Alves; Beck, Maristela de Oliveira; Sangoi Cardoso, Manuela; Duarte, Marta Maria Medeiros Frescura; Moresco, Rafael Noal; Soares, Félix Alexandre Antunes

2018-02-12

This study investigate the effects of high-intensity interval training (HIIT) on systemic levels of inflammatory and hormonal markers in postmenopausal women with metabolic syndrome (MS). Fifteen postmenopausal women with MS completed the training on treadmills. Functional, body composition parameters, maximal oxygen uptake (VO 2 max), and lipid profile were assessed before and after HIIT. Serum or plasma levels of cytokines and hormonal markers were measured along the intervention. The analysis of messenger RNA (mRNA) expression of these cytokines was performed in peripheral blood mononuclear cells (PBMC). VO 2 max and some anthropometric parameters were improved after HIIT, while decreased levels of proinflammatory markers and increased levels of interleukin-10 (IL-10) were also found. Adipokines were also modulated after 12 weeks or training. The mRNA expression of the studied genes was unchanged after HIIT. In conclusion, HIIT benefits inflammatory and hormonal axis on serum or plasma samples, without changes on PBMC of postmenopausal MS patients.

Self-rated health among pregnant women: associations with objective health indicators, psychological functioning, and serum inflammatory markers.

PubMed

Christian, Lisa M; Iams, Jay; Porter, Kyle; Leblebicioglu, Binnaz

2013-12-01

Biobehavioral correlates of self-rated health in pregnancy are largely unknown. The goals of this study were to examine, in pregnant women, associations of self-rated health with (1) demographics, objective health status, health behaviors, and psychological factors, and (2) serum inflammatory markers. In the second trimester of pregnancy, 101 women provided a blood sample, completed measures of psychosocial stress, health status, and health behaviors, and received a comprehensive periodontal examination. The following independently predicted poorer self-rated health: (1) greater psychological stress, (2) greater objective health diagnoses, (3) higher body mass index, and (4) past smoking (versus never smoking). Poorer self-rated health was associated with higher serum interleukin-1β (p = 0.02) and marginally higher macrophage migration inhibitory factor (p = 0.06). These relationships were not fully accounted for by behavioral/psychological factors. This study provides novel data regarding factors influencing subjective ratings of health and the association of self-rated health with serum inflammatory markers in pregnant women.

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

PubMed Central

Liu, Xiao-Lin; Pan, Qin; Zhang, Rui-Nan; Shen, Feng; Yan, Shi-Yan; Sun, Chao; Xu, Zheng-Jie; Chen, Yuan-Wen; Fan, Jian-Gao

2016-01-01

AIM To assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients. METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively. RESULTS Circulating miR-122, -16, -192 and -34a showed differential expression levels between NAFLD and CHB patients, and miR-34a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples (P < 0.01). Serum miR-122, -192 and -34a levels were correlated with steatosis (R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH. CONCLUSION Circulating miR-34a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH. PMID:27956809

Circulating 25-Hydroxyvitamin D Concentrations Are Correlated With Cardiometabolic Risk Among American Black and White Adolescents Living in a Year-Round Sunny Climate

PubMed Central

Parikh, Samip; Guo, De-huang; Pollock, Norman K.; Petty, Karen; Bhagatwala, Jigar; Gutin, Bernard; Houk, Chris; Zhu, Haidong; Dong, Yanbin

2012-01-01

OBJECTIVE Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population. RESEARCH DESIGN AND METHODS 25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14–18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP). RESULTS Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = −0.32, P < 0.01), fibrinogen (r = −0.05, P = 0.03), glucose (r = −0.16, P = 0.02), HOMA-IR (r = −0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = −0.10, P = 0.02), and diastolic BP (r = −0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates. CONCLUSIONS Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions. PMID:22410810

Association of Inflammation With Loss Of Ability to Walk 400 Meters: Longitudinal Findings From the Inchianti Study

PubMed Central

Vasunilashorn, Sarinnapha; Ferrucci, Luigi; Crimmins, Eileen M.; Bandinelli, Stefania; Guralnik, Jack M.; Patel, Kushang V.

2013-01-01

Objectives To examine relationships between eight markers of inflammation (interleukin [IL]-6, IL-6 receptor [R], C-reactive protein [CRP], tumor necrosis factor [TNF]-α, TNF receptor 1[R1], TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m. Design Prospective cohort study. Setting Older adults enrolled in the InvecchiareInChianti Study. Participants One thousand six community-dwelling participants aged 65+. Measurements The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined among participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicts loss of the ability to walk 400 m at six-year follow-up. Results After adjusting for covariates, individuals with aTNFR1 level in each of the top 3 quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up compared to those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to complete the 400 m walk at follow-up compared to participants with a score of 0. Conclusion These results bring additional evidence to the notion that inflammation is implicated in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve our prediction of functional prognosis. PMID:24083386

Association of inflammation with loss of ability to walk 400 meters: longitudinal findings from the Invecchiare in Chianti Study.

PubMed

Vasunilashorn, Sarinnapha; Ferrucci, Luigi; Crimmins, Eileen M; Bandinelli, Stefania; Guralnik, Jack M; Patel, Kushang V

2013-10-01

To examine relationships between eight markers of inflammation (interleukin (IL)-6, IL-6 receptor (R), C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, TNF receptor 1 (R1), TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m. Prospective cohort study. Older adults enrolled in the Invecchiare in Chianti Study. Community-dwelling participants aged 65 and older (N = 1,006). The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined in participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicted loss of the ability to walk 400 m at 6-year follow-up. After adjusting for covariates, individuals with a TNFR1 level in each of the highest three quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up than those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to walk 400 m at follow-up than participants with a score of 0. These results provide additional evidence that inflammation is a factor in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve prediction of functional prognosis. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Effect of Psyllium Fiber Supplementation on C-Reactive Protein: The Trial to Reduce Inflammatory Markers (TRIM)

PubMed Central

King, Dana E.; Mainous, Arch G.; Egan, Brent M.; Woolson, Robert F.; Geesey, Mark E.

2008-01-01

PURPOSE Recent evidence supports a significant association between the intake of dietary fiber and levels of inflammatory markers. The objective of this study was to determine whether daily fiber supplementation would reduce levels of inflammatory markers. METHODS This study was a prospective randomized controlled trial at a single university medical center. Participants were overweight or obese adults with no history of heart disease. The intervention was psyllium supplementation at either 7 or 14 g/d for 3 months compared with no supplements in a control group. The main outcome measure was change in level of high-sensitivity C-reactive protein (hsCRP) concentration; secondary outcomes included changes in interleukin-6 (IL-6) levels, fibrinogen levels, and white blood cell (WBC) count. Protocol completers attended at least 2 visits and took more than 75% of the prescribed fiber dose. RESULTS In this intent-to-treat analysis (n = 158), there were no significant differences between either of the 2 treatment groups and the control group in the amount of change in CRP, fibrinogen, or IL-6 levels or in WBC count (P>.05). In the analysis of protocol completers (n = 132), there also were no significant differences between the groups except for a small decrease in fibrinogen level in the high-fiber group (−6 mg/dL [−0.18 μmol/L] compared with 13 mg/dL [0.38 μmol/L] in the control group, P<.05). CONCLUSION Psyllium fiber supplementation did not significantly reduce CRP levels in overweight or obese individuals in this trial, and changes in other markers were not consistent. Further research is needed to determine whether other fibers or nutrients can reduce inflammatory markers. PMID:18332401

Genetic and Environmental Influences on Systemic Markers of Inflammation in Middle-Aged Male Twins

PubMed Central

Su, Shaoyong; Snieder, Harold; Miller, Andrew H.; Ritchie, James; Bremner, J. Douglas; Goldberg, Jack; Dai, Jun; Jones, Linda; Murrah, Nancy V.; Zhao, Jinying; Vaccarino, Viola

2008-01-01

Objectives The aims of this study were to determine the relative influence of genetic and environmental contributions to inflammatory biomarkers, and to what extent correlations among these markers are due to genetic or environmental factors. Methods We performed univariate and multivariate genetic analyses of four inflammatory markers: interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), C-reactive protein (CRP), and fibrinogen, in 166 (88 monozygotic and 78 dizygotic) middle-aged male twin pairs. Results The mean age (±SD) of the twins was 54 (±2.93) years. Heritability was substantial for CRP (0.61, 95% CI: 0.47–0.72) and moderate to fair for IL-6 (0.31, 0.13–0.46), sIL-6R (0.49, 0.30–0.76) and fibrinogen (0.52, 0.34–0.65). IL-6, CRP and fibrinogen showed significant correlations, but not with sIL-6R. Multivariate genetic analysis found that these correlations could be best explained by a common pathway model, where the common factor explained 27%, 73% and 25% of the variance of IL-6, CRP and fibrinogen, respectively. About 46% (95% CI: 21–64%) of the correlations among the three inflammatory markers could be explained by the genetic factors. After adjusting for covariates known to influence inflammation levels, heritability estimates were slightly decreased but the overall results remained similar. Conclusions A significant part of the variation in inflammatory marker levels is due to genetic influences. Furthermore, almost 50% of the shared variance among these biomarkers is due to a common genetic factor which likely plays a key role in the regulation of inflammation. PMID:18243214

Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults.

PubMed

Voon, Phooi Tee; Ng, Tony Kock Wai; Lee, Verna Kar Mun; Nesaretnam, Kalanithi

2011-12-01

Dietary fat type is known to modulate the plasma lipid profile, but its effects on plasma homocysteine and inflammatory markers are unclear. We investigated the effects of high-protein Malaysian diets prepared with palm olein, coconut oil (CO), or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease (CVD) in healthy adults. A randomized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects. The 3 test fats, namely palmitic acid (16:0)-rich palm olein (PO), lauric and myristic acid (12:0 + 14:0)-rich CO, and oleic acid (18:1)-rich virgin olive oil (OO), were incorporated at two-thirds of 30% fat calories into high-protein Malaysian diets. No significant differences were observed in the effects of the 3 diets on plasma total homocysteine (tHcy) and the inflammatory markers TNF-α, IL-1β, IL-6, and IL-8, high-sensitivity C-reactive protein, and interferon-γ. Diets prepared with PO and OO had comparable nonhypercholesterolemic effects; the postprandial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower (P < 0.05) than for the CO diet. Unlike the PO and OO diets, the CO diet was shown to decrease postprandial lipoprotein(a). Diets that were rich in saturated fatty acids prepared with either PO or CO, and an OO diet that was high in oleic acid, did not alter postprandial or fasting plasma concentrations of tHcy and selected inflammatory markers. This trial was registered at clinicaltrials.gov as NCT00941837.

Links between inflammation, amygdala reactivity, and social support in breast cancer survivors

PubMed Central

Muscatell, Keely A.; Eisenberger, Naomi I.; Dutcher, Janine M.; Cole, Steven W.; Bower, Julienne E.

2017-01-01

Psychosocial stress can affect inflammatory processes that have important consequences for cancer outcomes and the behavioral side effects of cancer treatment. To date, however, little is known about the upstream neural processes that may link psychosocial stressors and inflammation in cancer patients and survivors. To address this issue, 15 women who had been diagnosed with early-stage breast cancer and completed cancer treatment and 15 age- and ethnicity-matched women with no cancer history were recruited for a neuroimaging study. Participants provided a blood sample for levels of circulating inflammatory markers (CRP and IL-6), underwent an fMRI scan in which they completed a threat reactivity task designed to elicit activity in the amygdala, and reported their levels of perceived social attachment/ support. There were no significant differences between cancer survivors and controls in levels of CRP or IL-6, in amygdala reactivity to the socially threatening images, or in levels of perceived social support. However, results showed a strong, positive correlation between CRP concentration and left amygdala reactivity in the survivor group that was not apparent in controls. Higher levels of social support in the survivor group were also associated with reduced amygdala reactivity and CRP. These data suggest the possibility of a stronger “neural-immune pipeline” among breast cancer survivors, such that peripheral inflammation is more strongly associated with neural activity in threat-related brain regions. PMID:26384778

Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn’s Colitides

PubMed Central

Korolkova, Olga Y; Myers, Jeremy N; Pellom, Samuel T; Wang, Li; M’Koma, Amosy E

2015-01-01

BACKGROUND As accessible diagnostic approaches fail to differentiate between ulcerative colitis (UC) and Crohn’s colitis (CC) in one-third of patients with predominantly colonic inflammatory bowel disease (IBD), leading to inappropriate therapy, we aim to investigate the serum cytokine levels in these patients in search of molecular biometric markers delineating UC from CC. METHODS We measured 38 cytokines, chemokines, and growth factors using magnetic-bead-based multiplex immunoassay in 25 UC patients, 28 CC patients, and 30 controls. Our results are compared with those from a review of current literature regarding advances in serum cytokine profiles and associated challenges preventing their use for diagnostic/prognostic purposes. RESULTS Univariate analysis showed statistically significant increases of eotaxin, GRO, and TNF-α in UC patients compared to controls (Ctrl); interferon γ, interleukin (IL)-6, and IL-7 in CC group compared to Ctrl; and IL-8 in both UC and CC versus Ctrl. No cytokines were found to be different between UC and CC. A generalized linear model identified combinations of cytokines, allowing the identification of UC and CC patients, with area under the curve (AUC) = 0.936, as determined with receiver operating characteristic (ROC) analysis. CONCLUSIONS The current knowledge available about circulating cytokines in IBD is often contradictory. The development of an evidence-based tool using cytokines for diagnostic accuracy is still preliminary. PMID:26078592

Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFκB Pathway Suppression

PubMed Central

Zhou, Zhong'e; Tang, Yong; Chen, Chengjun; Lu, Yi; Liu, Liang

2016-01-01

Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression. PMID:27761470

The screening research of anti-inflammatory bioactive markers from different flowering phases of Flos Lonicerae Japonicae.

PubMed

Jiang, Min; Han, Yan-qi; Zhou, Meng-ge; Zhao, Hong-zhi; Xiao, Xue; Hou, Yuan-yuan; Gao, Jie; Bai, Gang; Luo, Guo-an

2014-01-01

Flos Lonicerae Japonicae (FLJ) is an important cash crop in eastern Asia, and it is an anti-inflammatory Traditional Chinese Medicine. There are large variations in the quality of the marketed FLJ products. To find marker ingredients useful for quality control, a tandem technology integrating ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF), principal component analysis (PCA), heat map analysis and hierarchical cluster analysis coupled with a NF-κB luciferase reporter gene assay were used to identify the different ingredients from the green bud, white bud, flowering stage and leaf stages, as well as to screen the anti-inflammatory activity of FLJ compositions. As flowering progressed, the anti-inflammatory effects of FLJ gradually decreased; however, chlorogenic acid, swertiamarin and sweroside should be used to evaluate the quality of FLJ products.

The Screening Research of Anti-Inflammatory Bioactive Markers from Different Flowering Phases of Flos Lonicerae Japonicae

PubMed Central

Jiang, Min; Han, Yan-qi; Zhou, Meng-ge; Zhao, Hong-zhi; Xiao, Xue; Hou, Yuan-yuan; Gao, Jie; Bai, Gang; Luo, Guo-an

2014-01-01

Flos Lonicerae Japonicae (FLJ) is an important cash crop in eastern Asia, and it is an anti-inflammatory Traditional Chinese Medicine. There are large variations in the quality of the marketed FLJ products. To find marker ingredients useful for quality control, a tandem technology integrating ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF), principal component analysis (PCA), heat map analysis and hierarchical cluster analysis coupled with a NF-κB luciferase reporter gene assay were used to identify the different ingredients from the green bud, white bud, flowering stage and leaf stages, as well as to screen the anti-inflammatory activity of FLJ compositions. As flowering progressed, the anti-inflammatory effects of FLJ gradually decreased; however, chlorogenic acid, swertiamarin and sweroside should be used to evaluate the quality of FLJ products. PMID:24809338

Kalirin and CHD7: novel endothelial dysfunction indicators in circulating extracellular vesicles from hypertensive patients with albuminuria

PubMed Central

de la Cuesta, Fernando; Baldan-Martin, Montserrat; Moreno-Luna, Rafael; Alvarez-Llamas, Gloria; Gonzalez-Calero, Laura; Mourino-Alvarez, Laura; Sastre-Oliva, Tamara; López, Juan A.; Vázquez, Jesús; Ruiz-Hurtado, Gema; Segura, Julian; Vivanco, Fernando; Ruilope, Luis M.; Barderas, Maria G.

2017-01-01

Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies. Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation. Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria. PMID:28152519

Changes in body weight, C-reactive protein, and total adiponectin in non-obese women after 12 months of a small-volume, home-based exercise program.

PubMed

Mediano, Mauro Felippe Felix; Neves, Fabiana Alves; Cunha, Alessandra Cordeiro de Souza Rodrigues; Souza, Erica Patricia Garcia de; Moura, Anibal Sanchez; Sichieri, Rosely

2013-01-01

Our objective was to evaluate the effects of small-volume, home-based exercise combined with slight caloric restriction on the inflammatory markers C-reactive protein and adiponectin. In total, 54 women were randomly assigned to one of two groups for exercise intervention: the control or home-based exercise groups. Weight, waist and hip circumferences, and inflammatory markers were measured at baseline and after 6 and 12 months. Women allocated to the home-based exercise group received a booklet explaining the physical exercises to be practiced at home at least 3 times per week, 40 minutes per session, at low-to-moderate intensity. All participants received dietary counseling aimed at reducing caloric intake by 100-300 calories per day, with a normal distribution of macro-nutrients (26-28% of energy as fat). Clinicaltrials.gov: NCT01206413 RESULTS: The home-based exercise group showed a significantly greater reduction in weight and body mass index at six months, but no difference between groups was observed thereafter. With regard to the inflammatory markers, a greater but non-statistically significant reduction was found for C-reactive protein in the home-based exercise group at six months; however, this difference disappeared after adjusting for weight change. No differences in adiponectin were found at the 6- or 12-month follow-up. Small-volume, home-based exercise did not promote changes in inflammatory markers independent of weight change.

Cytokine Responses to Acute Exercise in Healthy Older Adults: The Effect of Cardiorespiratory Fitness

PubMed Central

Windsor, Mark T.; Bailey, Tom G.; Perissiou, Maria; Meital, Lara; Golledge, Jonathan; Russell, Fraser D.; Askew, Christopher D.

2018-01-01

Markers of chronic inflammation increase with aging, and are associated with cardiovascular disease prevalence and mortality. Increases in fitness with exercise training have been associated with lower circulating concentrations of cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6]) and higher circulating concentrations of anti-inflammatory cytokines (interleukin-10 [IL-10]). However, the effect of cardiorespiratory fitness on acute cytokine responses to a single bout of exercise in healthy older individuals is unknown. We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha (TNF-α) and IL-10 to a bout of moderate-intensity continuous and higher-intensity interval exercise between older individuals with higher and lower levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6±2.8 mL.kg−1.min−1) and fourteen higher-fit participants (VO2peak: 37.4±5.9 mL.kg−1.min−1) completed three 24 min experimental protocols in a randomized order: (1) moderate-intensity continuous exercise (40% of peak power output [PPO]); (2) higher-intensity interval exercise (12 × 1 min intervals at 70% PPO separated by 1 min periods at 10% PPO); or (3) non-exercise control. Plasma cytokines were measured at rest, immediately after, and during 90 min of recovery following exercise or control. Plasma IL-6 concentrations at baseline were greater in the higher-fit compared to the lower-fit group (P = 0.02), with no difference in plasma IL-10 or TNF-α concentrations at baseline between groups. Plasma IL-6 and IL-10 concentrations in both groups increased immediately after all protocols (IL-6: P = 0.02, IL-10: P < 0.01). However, there was no difference in the IL-6 and IL-10 response between the exercise and non-exercise (control) protocols. After all protocols, no changes in plasma TNF-α concentrations were observed in either the higher- or lower-fit groups. In this study, basal concentrations of circulating IL-6 were elevated in older individuals with higher levels of cardiorespiratory fitness. However, changes in plasma cytokine concentrations after exercise were not different to changes after non-exercise control in both the lower- and higher-fit groups. PMID:29599722

Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology.

PubMed

Gold, Bert; Cankovic, Milena; Furtado, Larissa V; Meier, Frederick; Gocke, Christopher D

2015-05-01

Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Identification of Apolipoprotein C-I as a Potential Wilms’ Tumor Marker after Excluding Inflammatory Factors

PubMed Central

Zhang, Junjie; Guo, Fei; Wang, Lei; Zhao, Wei; Zhang, Da; Yang, Heying; Yu, Jiekai; Niu, Lili; Yang, Fuquan; Zheng, Shu; Wang, Jiaxiang

2014-01-01

Wilms’ tumor is one of the most common malignant tumors observed in children, and its early diagnosis is important for late-stage treatment and prognosis. We previously screened and identified protein markers for Wilms’ tumor; however, these markers lacked specificity, and some were associated with inflammation. In the current study, serum samples from children with Wilms’ tumors were compared with those of healthy controls and patients with systemic inflammatory response syndrome (SIRS). After exclusion of factors associated with inflammation, specific protein markers for Wilms’ tumors were identified. After comparing the protein peak values obtained from all three groups, a protein with a m/z of 6438 Da was specified. Purification and identification of the target protein using high-pressure liquid chromatography (HPLC) and two-dimensional liquid chromatography-linearion trap mass spectrometry(2D-LC-LTQ-MS) mass spectrometry, respectively, revealed that it was apolipoprotein C-I (APO C-I). Thus, APO C-I is a specific protein marker for Wilms’ tumor. PMID:25222555

Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis.

PubMed

Miyake, Hiromu; Li, Bo; Lee, Carol; Koike, Yuhki; Chen, Yong; Seo, Shogo; Pierro, Agostino

2018-05-01

Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. Level IV. Copyright © 2018. Published by Elsevier Inc.

Inflammatory markers in SIRS, sepsis and septic shock.

PubMed

Herzum, I; Renz, H

2008-01-01

Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.

Bioaerosol exposure and circulating biomarkers in a panel of elderly subjects and healthy young adults.

PubMed

Faridi, Sasan; Naddafi, Kazem; Kashani, Homa; Nabizadeh, Ramin; Alimohammadi, Mahmood; Momeniha, Fatemeh; Faridi, Sholeh; Niazi, Sadegh; Zare, Ahad; Gholampour, Akbar; Hoseini, Mohammad; Pourpak, Zahra; Hassanvand, Mohammad Sadegh; Yunesian, Masud

2017-09-01

Numerous studies have found that risk of cardiovascular diseases is associated with increased blood levels of circulating markers of systemic inflammation. We investigated associations of acute exposure to bioaerosols (bacteria and fungi) with blood markers of inflammation and coagulation using panels of elderly subjects and healthy young adults. We conducted a panel study of 44 nonsmoker elderly subjects in a retirement communities and a panel study of 40 healthy young adults living in a school dormitory within Tehran city, Iran. Blood sample biomarkers were measured weekly over 6weeks and including high sensitive C-reactive protein (hsCRP), tumor necrosis factor-soluble receptor-II (sTNF-RII), von Willebrand factor (vWF), white blood cells (WBC) count and interleukin-6 (IL-6). We found significant positive associations for IL-6 and WBC with exposure to Aspergillus spp. (As), Cladosporium spp. (Cl), Penicillium spp. (Pe), total fungi (TF) and Micrococcus spp. (MI); vWF with Cl and MI; sTNF-RII with Staphylococcus spp. (ST) in healthy young adults from the current-day and multiday averages. For elderly subjects, we observed significant positive associations for hsCRP, sTNF-RII and WBC with exposure to MI, but not with ST and total bacteria (TB). Our results showed the strongest significant positive associations for IL-6 with MI, ST and TB in elderly people. In addition, IL-6 was also positively associated with As, Cl and Pe in elderly. Also, the results showed that increase of vWF was significantly associated with bacterial and fungal aerosols, except Bacillus spp. (BA) at some lags in elderly subjects. Pooled results support the pivotal role of bioaerosols in increasing the level of some of inflammatory biomarkers, especially IL-6 and WBC in healthy young adults but possibly also in elderly people. Copyright © 2017 Elsevier B.V. All rights reserved.

Nuclear factor kappa B in patients with a history of unstable angina: case re-opened.

PubMed

Mozzini, Chiara; Garbin, Ulisse; Stranieri, Chiara; Salandini, Giulia; Pesce, Giancarlo; Fratta Pasini, Anna Maria; Cominacini, Luciano

2018-06-01

This study aims at assessing NF-kB activity in unstable angina (UA) patients free of symptoms after a 1 year follow-up (1YFU). Plasma oxidized low-density lipoproteins (oxLDL), circulating NF-kB, Interleukin 6 (IL-6) and Interleukin 1β (IL-1β), high-sensitivity C-reactive protein (hs-CRP), as markers of oxidative stress and inflammation and plasma double-stranded DNA (ds-DNA), as marker of Neutrophil Extracellular Traps (NETs), were measured in 23 of the previously enrolled 27 UA patients. These measurements were compared to the UA data at baseline, and then compared to the data derived from the stable angina (SA) and controls (C) enrolled in our previous study (we demonstrated that UA had higher levels of NF-kB compared to SA and C). After a 1YFU, UA patients show a significant decrease in NF-kB, IL-6, hs-CRP, oxLDL, and ds-DNA plasma levels (p < 0.001) and in IL-1β and White Blood Cells (WBC) (p < 0.005), without differences in lipid and glucose assessment. If compared to SA and C, UA after a 1YFU have higher levels of NF-kB, IL-6, ds-DNA, WBC, and oxLDL compared to C (p < 0.001), but only IL-6 is higher than SA (p < 0.001). No differences are found in lipid and glucose assessment. After a 1YFU, patients with a history of UA improve their oxidative and inflammatory status, such as the levels of circulating ds-DNA, without achieving the status of C. They become comparable to SA subjects. This study provides new insight on the multiple and apparently contradictory facets of NF-kB in UA and on its possible role as mediator in NETs' formation.

Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study.

PubMed

Simpson, William; Steiner, Meir; Coote, Marg; Frey, Benicio N

2016-01-01

Perinatal depressive symptoms often co-occur with other inflammatory morbidities of pregnancy. The goals of our study were 1) to examine whether changes in inflammatory markers from the third trimester of pregnancy to 12 weeks postpartum were associated with changes in depressive symptoms; 2) to examine whether third trimester inflammatory markers alone were predictive of postpartum depressive symptoms; and 3) to examine the relationship between inflammatory markers and depressive symptoms during the third trimester of pregnancy and at 12 weeks postpartum. Thirty-three healthy pregnant women were recruited from the Women's Health Concerns Clinic at St. Joseph's Healthcare in Hamilton, Canada. The impact of depressive symptoms on the levels of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) at the third trimester of pregnancy, at 12 weeks postpartum, and across time was assessed using linear and mixed-model regression. Regression analysis revealed no significant association between depressive symptoms and any of the candidate biomarkers during pregnancy, at 12 weeks postpartum, or over time. Pregnancy depressive symptoms (p > 0.001), IL-6 (p = 0.025), and IL-10 (p = 0.006) were significant predictors of postpartum Edinburgh Perinatal Depression Scale (EPDS) score. Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.

Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

PubMed

Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

2015-10-01

The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

Taxonomic applicability of inflammatory cytokines in adverse outcome pathway (AOP) development

EPA Science Inventory

Cytokines, low-molecular-weight messenger proteins that act as intercellular immunomodulatory signals, have become a mainstream preclinical marker for assessing the systemic inflammatory response to external stressors. The challenge is to quantitate from healthy subjects cytokine...

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma

PubMed Central

Palmieri, Giuseppe; Satriano, Sabrina MR; Budroni, Mario; Cossu, Antonio; Tanda, Francesco; Canzanella, Sergio; Caracò, Corrado; Simeone, Ester; Daponte, Antonio; Mozzillo, Nicola; Comella, Giuseppe; Castello, Giuseppe; Ascierto, Paolo A

2006-01-01

Background Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). Methods One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Results Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Conclusion Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease. PMID:17107608

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma.

PubMed

Palmieri, Giuseppe; Satriano, Sabrina M R; Budroni, Mario; Cossu, Antonio; Tanda, Francesco; Canzanella, Sergio; Caracò, Corrado; Simeone, Ester; Daponte, Antonio; Mozzillo, Nicola; Comella, Giuseppe; Castello, Giuseppe; Ascierto, Paolo A

2006-11-15

Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (> or =2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease.

Phytochemical and anti-inflammatory activities of aqueous leaf extract of Indian borage (oregano) on rats induced with inflammation.

PubMed

Akinbo, David Bolaji; Onyeaghala, Augustine A; Emomidue, Jennifer Ochuko; Ogbhemhe, Stephanie Okhuriafe; Okpoli, Henry Chijindu

2018-03-30

The Indian borage (Plectranthus amboinicus) also called Oregano contains many effective antioxidants, which includes caffeic acid, rosmarinic acid and flavonoids. It has been employed in traditional medicine for its several health benefits including the prevention and cure of many debilitating diseases. Anti-inflammatory properties of Plectranthus amboinicus grown within this environment have not been adequately explored. The protective and therapeutic effects of Oregano against endotoxaemia and inflammation were evaluated using lipopolysaccharide (LPS)-induced rat models. A total of 30 Wistar rats were randomly selected for this study and divided into six groups, with each group having 5 rats. Inflammation was induced on appropriate animal groups using LPS injection at a concentration of 4 mg/kg. Aqueous leaf extract of Indian borage was administered orally in four doses (100 mg/kg, 200 mg/kg, 400 mg/kg post-LPS exposure and 150 mg/kg pre-LPS exposure) to respective treatment rat groups. Haematological profile, toxicity profile of liver and kidney and levels of biomarkers of inflammation were assayed using standard methods. Rats injected with LPS showed severe anaemia and marked leucopoenia with significant decrease in monocytes compared to the control group (p< 0.05). There was increased expression of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) (p< 0.05) in the peripheral circulation of rats exposed to LPS. Treatment with Indian borage significantly (p< 0.05) reduced the toxic effects in the LPS-treated animals and attenuated the increase in the expression of circulating proinflammatory cytokines; tumor necrosis factor alpha (TN-Fα) and interleukin-8 (IL-8) caused by LPS. Indian borage pretreatment also significantly (p< 0.05) counteracted the associated haematological dyscrasias caused by exposure to LPS. The extract elicited a significant protective effect on the kidney and liver as evidenced by the decreased renal markers and hepatic enzyme activities when compared with the control. The extract demonstrated protective and suppressive role against the overexpression of inflammatory mediators by ameliorating the induced inflammation and endotoxaemic conditions in the affected rat groups thereby validating its folkloric use. Our study thus reveals that the extract might be an active, natural and non-toxic drug lead against endotoxaemia-induced inflammation and toxicity.

Occupational exposure to diesel engine exhaust and alterations in immune/inflammatory markers: a cross-sectional molecular epidemiology study in China.

PubMed

Bassig, Bryan A; Dai, Yufei; Vermeulen, Roel; Ren, Dianzhi; Hu, Wei; Duan, Huawei; Niu, Yong; Xu, Jun; Shiels, Meredith S; Kemp, Troy J; Pinto, Ligia A; Fu, Wei; Meliefste, Kees; Zhou, Baosen; Yang, Jufang; Ye, Meng; Jia, Xiaowei; Meng, Tao; Wong, Jason Y Y; Bin, Ping; Hosgood, H Dean; Hildesheim, Allan; Silverman, Debra T; Rothman, Nathaniel; Zheng, Yuxin; Lan, Qing

2017-10-26

The relationship between diesel engine exhaust (DEE), a known lung carcinogen, and immune/inflammatory markers that have been prospectively associated with lung cancer risk is not well understood. To provide insight into these associations, we conducted a cross-sectional molecular epidemiology study of 54 males highly occupationally exposed to DEE and 55 unexposed male controls from representative workplaces in China. We measured plasma levels of 64 immune/inflammatory markers in all subjects using Luminex bead-based assays, and compared our findings to those from a nested case-control study of these markers and lung cancer risk, which had been conducted among never-smoking women in Shanghai using the same multiplex panels. Levels of nine markers that were associated with lung cancer risk in the Shanghai study were altered in DEE-exposed workers in the same direction as the lung cancer associations. Among these, associations with the levels of CRP (β= -0.53; P = 0.01) and CCL15/MIP-1D (β = 0.20; P = 0.02) were observed in workers exposed to DEE and with increasing elemental carbon exposure levels (Ptrends <0.05) in multivariable linear regression models. Levels of a third marker positively associated with an increased lung cancer risk, CCL2/MCP-1, were higher among DEE-exposed workers compared with controls in never and former smokers, but not in current smokers (Pinteraction = 0.01). The immunological differences in these markers in DEE-exposed workers are consistent with associations observed for lung cancer risk in a prospective study of Chinese women and may provide some insight into the mechanistic processes by which DEE causes lung cancer. Published by Oxford University Press 2017.

Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes

PubMed Central

Glennie, Nelson D.; Volk, Susan W.

2017-01-01

Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis. PMID:28419151

HETEROTYPIC INTERACTIONS ENABLED BY POLARIZED NEUTROPHIL MICRODOMAINS MEDIATE THROMBO-INFLAMMATORY INJURY

PubMed Central

Hidalgo, Andrés; Chang, Jungshan; Jang, Jung-Eun; Peired, Anna J.; Chiang, Elaine Y.; Frenette, Paul S.

2009-01-01

Selectins and their ligands mediate leukocyte rolling allowing interactions with chemokines that lead to integrin activation and arrest. Here, we demonstrate that E-selectin is critical to induce a secondary wave of activating signals transduced specifically by E-selectin ligand-1, that induces polarized, activated αMβ2 integrin clusters at the leading edge of crawling neutrophils, allowing the capture of circulating erythrocytes or platelets. In a humanized model of sickle cell disease (SCD), the capture of erythrocytes by αMβ2 microdomains leads to acute lethal vascular occlusions. In a model of transfusion-related acute lung injury, polarized neutrophils capture circulating platelets, resulting in the generation of oxidative species that produces vascular damage and lung injury. Inactivation of E-selectin or αMβ2 prevented tissue injury in both inflammatory models, suggesting broad implications of this paradigm in thrombo-inflammatory diseases. These results indicate that endothelial selectins can influence neutrophil behavior beyond its canonical rolling step through delayed, organ-damaging, polarized activation. PMID:19305412

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu; Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751; Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissuesmore » that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron increased the levels of IL-1β, IL-6 and TNF-α in lung tissues at high altitudes. • Trolox alleviated the iron-induced histological and biochemical changes to the lungs.« less

Role of Anti-Inflammatory Cytokines on Muscle Mass and Performance Changes in Elderly Men and Women.

PubMed

Rossi, A P; Budui, S; Zoico, E; Caliari, C; Mazzali, G; Fantin, F; D'Urbano, M; Paganelli, R; Zamboni, M

2017-01-01

Investigate the presence of a correlation between systemic inflammatory profile of community-dwelling individuals and the loss of muscular mass and performance in old age over a 4.5y follow-up, focusing on the role of anti-inflammatory cytokines in muscular changes in elderly. Longitudinal clinical study. Subjects were randomly selected from lists of 11 general practitioners in the city of Verona, Italy. The study included 120 subjects, 92 women and 28 men aged 72.27±2.06 years and with BMI of 26.52±4.07 kg/m2 at baseline. Six minutes walking test (6MWT), appendicular and leg fat free mass (FFM) as measured with Dual Energy X-ray absorptiometry, were obtained at baseline and after 4.5 years (4.5y) of mean follow-up. Height, weight, body mass index (BMI), and circulating levels of TNFα, IL-4, IL-10, and IL-13 were evaluated at baseline. A significant reduction of appendicular FFM, leg FFM and 6MWT performance (all p<0.001) was observed after 4.5 y follow-up. In a stepwise regression model, considering appendicular FFM decline as dependent variable, lnIL-4, BMI, baseline appendicular FFM, lnTNFα and lnIL-13 were significant predictors of appendicular FFM decline explaining 30.8% of the variance. While building a stepwise multiple regression considering leg FFM as a dependent variable, lnIL-4, BMI and leg FFM were significant predictors of leg FFM decline and explained 27.4% of variance. When considering 6MWT decline as a dependent variable, baseline 6MWT, lnIL-13 and lnTNFα were significant predictors of 6MWT decline to explain 22.9% of variance. Our study suggest that higher serum levels of anti-inflammatory markers, and in particular IL-4 and IL-13, may play a protective role on FFM and performance maintenance in elderly subjects.

Loneliness, Depression, and Inflammation: Evidence from the Multi-Ethnic Study of Atherosclerosis.

PubMed

Mezuk, Briana; Choi, Moon; DeSantis, Amy S; Rapp, Stephen R; Diez Roux, Ana V; Seeman, Teresa

2016-01-01

Both objective and subjective aspects of social isolation have been associated with alterations in immune markers relevant to multiple chronic diseases among older adults. However, these associations may be confounded by health status, and it is unclear whether these social factors are associated with immune functioning among relatively healthy adults. The goal of this study was to examine the associations between perceived loneliness and circulating levels of inflammatory markers among a diverse sample of adults. Data come from a subset of the Multi-Ethnic Study of Atherosclerosis (n = 441). Loneliness was measured by three items derived from the UCLA Loneliness Scale. The association between loneliness and C-reactive protein (CRP) and fibrinogen was assessed using multivariable linear regression analyses. Models were adjusted for demographic and health characteristics. Approximately 50% of participants reported that they hardly ever felt lonely and 17.2% felt highly lonely. Individuals who were unmarried/unpartnered or with higher depressive symptoms were more likely to report being highly lonely. There was no relationship between perceived loneliness and ln(CRP) (β = -0.051, p = 0.239) adjusting for demographic and health characteristics. Loneliness was inversely associated with ln(fibrinogen) (β = -0.091, p = 0.040), although the absolute magnitude of this relationship was small. These results indicate that loneliness is not positively associated with fibrinogen or CRP among relatively healthy middle-aged adults.

Loneliness, Depression, and Inflammation: Evidence from the Multi-Ethnic Study of Atherosclerosis

PubMed Central

Mezuk, Briana; Choi, Moon; DeSantis, Amy S.; Rapp, Stephen R.; Diez Roux, Ana V.; Seeman, Teresa

2016-01-01

Objective Both objective and subjective aspects of social isolation have been associated with alterations in immune markers relevant to multiple chronic diseases among older adults. However, these associations may be confounded by health status, and it is unclear whether these social factors are associated with immune functioning among relatively healthy adults. The goal of this study was to examine the associations between perceived loneliness and circulating levels of inflammatory markers among a diverse sample of adults. Methods Data come from a subset of the Multi-Ethnic Study of Atherosclerosis (n = 441). Loneliness was measured by three items derived from the UCLA Loneliness Scale. The association between loneliness and C-reactive protein (CRP) and fibrinogen was assessed using multivariable linear regression analyses. Models were adjusted for demographic and health characteristics. Results Approximately 50% of participants reported that they hardly ever felt lonely and 17.2% felt highly lonely. Individuals who were unmarried/unpartnered or with higher depressive symptoms were more likely to report being highly lonely. There was no relationship between perceived loneliness and ln(CRP) (β = -0.051, p = 0.239) adjusting for demographic and health characteristics. Loneliness was inversely associated with ln(fibrinogen) (β = -0.091, p = 0.040), although the absolute magnitude of this relationship was small. Conclusion These results indicate that loneliness is not positively associated with fibrinogen or CRP among relatively healthy middle-aged adults. PMID:27367428

Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated impairment of mouse islet function.

PubMed

Caton, P W; Kieswich, J; Yaqoob, M M; Holness, M J; Sugden, M C

2011-12-01

Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD(+) biosynthesis, exists as intracellular NAMPT (iNAMPT) and extracellular NAMPT (eNAMPT). eNAMPT, secreted from adipose tissue, promotes insulin secretion. Administration of nicotinamide mononucleotide (NMN), a product of the eNAMPT reaction, corrects impaired islet function in Nampt ( +/- ) mice. One of its potential targets is the NAD(+)-dependent deacetylase sirtuin 1. We hypothesised that altered NAMPT activity might contribute to the suppression of islet function associated with inflammation, and aimed to determine whether NMN could improve cytokine-mediated islet dysfunction. Acute effects of NMN on cytokine-mediated islet dysfunction were examined in islets incubated with TNFα and IL1β, and in mice fed a fructose-rich diet (FRD) for 16 weeks. Changes in iNAMPT, eNAMPT and inflammation levels were determined in FRD-fed mice. FRD-fed mice displayed markedly lower levels of circulating eNAMPT, with impaired insulin secretion and raised islet expression of Il1b. NMN administration lowered Il1b expression and restored suppressed insulin secretion in FRD-fed mice. NMN also restored insulin secretion in islets cultured with pro-inflammatory cytokines. The changes in islet function corresponded with changes in key markers of islet function and differentiation. The anti-inflammatory effects of NMN were partially blocked by inhibition of sirtuin 1. Chronic fructose feeding causes severe islet dysfunction in mice. Onset of beta cell failure in FRD-fed mice may occur via lowered secretion of eNAMPT, leading to increased islet inflammation and impaired beta cell function. Administration of exogenous NMN to FRD-fed mice corrects inflammation-induced islet dysfunction. Modulation of this pathway may be an attractive target for amelioration of islet dysfunction associated with inflammation.

A Prospective Study of Periodontal Disease and Risk of Gastric and Duodenal Ulcer in Male Health Professionals

PubMed Central

Boylan, Matthew R; Khalili, Hamed; Huang, Edward S; Michaud, Dominique S; Izard, Jacques; Joshipura, Kaumudi J; Chan, Andrew T

2014-01-01

OBJECTIVES: Periodontal disease has been associated with higher circulating levels of inflammatory markers and conditions associated with chronic inflammation, including vascular disease, diabetes mellitus, and cancer. Limited data exist on the relationship between periodontal disease and gastric and duodenal ulcer. METHODS: We conducted a prospective cohort study of 49,120 men in the Health Professionals Follow-up Study, aged 40–75 years at enrollment in 1986. Biennially, we assessed periodontal disease, tooth loss, and other risk factors for gastric and duodenal ulcer. We validated diagnoses of gastric and duodenal ulcer through medical record review. We used Cox proportional hazards modeling, adjusting for potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 138 cases of gastric ulcer and 124 cases of duodenal ulcer with available information on Helicobacter pylori status over 24 years of follow-up. After adjustment for risk factors, including smoking and regular use of aspirin and non-steroidal anti-inflammatory drugs, men with periodontal disease with bone loss had a multivariate HR of ulcer of 1.62 (95% CI, 1.24–2.12). Periodontal disease appeared to be associated with a similar risk of developing ulcers that were H. pylori negative (HR 1.75; 95% CI, 1.26–2.43) than H. pylori positive (HR 1.40; 95% CI, 0.87-2.24), as well as ulcers in the stomach (HR 1.75; 95% CI, 1.21–2.53) than ulcers in the duodenum (HR 1.47; 95% CI, 0.98–2.19). CONCLUSIONS: Periodontal disease is associated with an increased risk of incident gastric and duodenal ulcer. This relationship may be mediated by alterations in the oral and gastrointestinal microbiome and/or systemic inflammatory factors. PMID:24522171

A prospective study of periodontal disease and risk of gastric and duodenal ulcer in male health professionals.

PubMed

Boylan, Matthew R; Khalili, Hamed; Huang, Edward S; Michaud, Dominique S; Izard, Jacques; Joshipura, Kaumudi J; Chan, Andrew T

2014-02-13

Periodontal disease has been associated with higher circulating levels of inflammatory markers and conditions associated with chronic inflammation, including vascular disease, diabetes mellitus, and cancer. Limited data exist on the relationship between periodontal disease and gastric and duodenal ulcer. We conducted a prospective cohort study of 49,120 men in the Health Professionals Follow-up Study, aged 40-75 years at enrollment in 1986. Biennially, we assessed periodontal disease, tooth loss, and other risk factors for gastric and duodenal ulcer. We validated diagnoses of gastric and duodenal ulcer through medical record review. We used Cox proportional hazards modeling, adjusting for potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 138 cases of gastric ulcer and 124 cases of duodenal ulcer with available information on Helicobacter pylori status over 24 years of follow-up. After adjustment for risk factors, including smoking and regular use of aspirin and non-steroidal anti-inflammatory drugs, men with periodontal disease with bone loss had a multivariate HR of ulcer of 1.62 (95% CI, 1.24-2.12). Periodontal disease appeared to be associated with a similar risk of developing ulcers that were H. pylori negative (HR 1.75; 95% CI, 1.26-2.43) than H. pylori positive (HR 1.40; 95% CI, 0.87-2.24), as well as ulcers in the stomach (HR 1.75; 95% CI, 1.21-2.53) than ulcers in the duodenum (HR 1.47; 95% CI, 0.98-2.19). Periodontal disease is associated with an increased risk of incident gastric and duodenal ulcer. This relationship may be mediated by alterations in the oral and gastrointestinal microbiome and/or systemic inflammatory factors.

Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder.

PubMed

Wilson, C Brad; McLaughlin, Leslie D; Ebenezer, Philip J; Nair, Anand R; Dange, Rahul; Harre, Joseph G; Shaak, Thomas L; Diamond, David M; Francis, Joseph

2014-01-01

Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines (PIC) are elevated during the progression of the disorder. Currently, the only approved pharmacologic treatments for PTSD are the selective-serotonin reuptake inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness. Thus, this study sought to analyze the effects of the SSRI sertraline on inflammation and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. We hypothesized that sertraline would diminish inflammatory components and increase 5-HT but might also affect levels of other neurotransmitters, particularly NE. PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle. The animals were subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and normalized 5-HT levels in the central nervous system (CNS). In contrast, sertraline produced elevations in NE in the CNS and systemic circulation of SSRI treated PTSD and control groups. This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting.

Heart-rate reduction by If-channel inhibition with ivabradine restores collateral artery growth in hypercholesterolemic atherosclerosis.

PubMed

Schirmer, Stephan H; Degen, Achim; Baumhäkel, Magnus; Custodis, Florian; Schuh, Lisa; Kohlhaas, Michael; Friedrich, Erik; Bahlmann, Ferdinand; Kappl, Reinhard; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2012-05-01

Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth. The I(f)-channel inhibitor ivabradine reduced heart rate by 11% in wild-type and 15% in apolipoprotein E (ApoE)(-/-) mice and restored endothelium-dependent relaxation in aortic rings of ApoE(-/-) mice. Microsphere perfusion and angiographies demonstrated that ivabradine did not change hindlimb perfusion in wild-type mice but improved perfusion in ApoE(-/-) mice from 40.5 ± 15.8-60.2 ± 18.5% ligated/unligated hindlimb. Heart rate reduction (13%) with metoprolol failed to improve endothelial function and perfusion. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, and eNOS activity were increased in collateral tissue following ivabradine treatment of ApoE(-/-) mice. Co-treatment with nitric oxide-inhibitor N (G)-nitro-L-arginine methyl ester abolished the effects of ivabradine on arteriogenesis. Following ivabradine, classical inflammatory cytokine expression was lowered in ApoE(-/-) circulating mononuclear cells and in plasma, but unaltered in collateral-containing hindlimb tissue, where numbers of perivascular macrophages also remained unchanged. However, ivabradine reduced expression of anti-arteriogenic cytokines CXCL10and CXCL11 and of smooth muscle cell markers smoothelin and desmin in ApoE(-/-) hindlimb tissue. Endothelial nitric oxide synthase and inflammatory cytokine expression were unchanged in wild-type mice. Ivabradine did not affect cytokine production in HUVECs and THP1 mononuclear cells and had no effect on the membrane potential of HUVECs in patch-clamp experiments. Ivabradine-induced HRR stimulates adaptive collateral artery growth. Important contributing mechanisms include improved endothelial function, eNOS activity, and modulation of inflammatory cytokine gene expression.

Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-γ+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease.

PubMed

Globig, Anna-Maria; Hennecke, Nadine; Martin, Bianca; Seidl, Maximilian; Ruf, Günther; Hasselblatt, Peter; Thimme, Robert; Bengsch, Bertram

2014-12-01

Skewed T helper (TH) cell responses and specific functions of TH1, TH2, TH17, and Treg cells have been implicated in the pathogenesis of inflammatory bowel disease (IBD) that led to the establishment of the pathogenic TH1/TH2 and TH17/Treg cell imbalance paradigms. However, the relevant TH cell population driving mucosal inflammation is still unknown. We performed a comprehensive TH cell profiling of circulating and intestinal lymphocytes isolated from patients with Crohn's disease (CD; n = 69) and ulcerative colitis (UC; n = 41) undergoing endoscopy or surgical resection and compared them with healthy controls (n = 45). Mucosal inflammation was assessed endoscopically and histologically. TH cells were analyzed by flow cytometric evaluation of cytokine production and differentiation marker expression. Specialized TH cell populations were enriched in the intestinal mucosa compared with peripheral blood. Specifically, we observed a concomitant upregulation of TH17 cells and Tregs in active inflammatory lesions in patients with both CD and UC compared with quiescent/mildly inflamed lesions and healthy tissue. Of note, interferon γ+ interleukin (IL)-17+coproducing CD4+ T cells with high expression of T-bet, CD26, and IL-22 resembling recently described pathogenic TH17 cells were specifically enriched in the inflamed mucosal tissue. Our results argue against the controversial TH1/TH2 or TH17/Treg paradigms. In contrast, they suggest that a subpopulation of TH17 cells sharing a TH1 signature may be specifically involved in intestinal inflammation in CD and UC. These findings provide a better understanding of IBD pathogenesis and may help explain the efficacy of anti-IL-12p40/IL-23 and failure of anti-IL-17A therapies despite the enrichment of TH17 cells.

Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity

PubMed Central

2011-01-01

Background Circulating levels of novel long-chain hydroxy fatty acids (called GTAs) were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC), independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation. Methods GTAs were extracted from commercially available bulk human serum and then chromatographically separated into enriched (GTA-positive) and depleted (GTA-negative) fractions. SW620, MCF7 and LPS stimulated RAW264.7 cells were treated with various concentrations of the GTA-positive and GTA-negative extracts, and the effects on cell growth and inflammation determined. Results Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels. In RAW264.7 mouse macrophage cells, incubation with enriched fractions prior to treatment with LPS blocked the induction of several pro-inflammatory markers including nitric oxide, TNFα, IL-1β, NOS2 and COX2. Conclusions Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity. These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC. PMID:21586136

Advances in the mechanisms and early warning indicators of the postoperative cognitive dysfunction after the extracorporeal circulation.

PubMed

Liu, Chao; Han, Jian-ge

2015-02-01

The high incidence of postoperative cognitive dysfunction (POCD) after extracorporeal circulation has seriously affected the prognosis and quality of life. Its mechanism may involve the inflammatory response and oxidative stress,the excessive phosphorylation of tau protein, the decreased blood volume and oxygen in the cerebral cortex. Appropriate early warning indicators of POCD after the extracorporeal circulation should be chosen to facilitate the cross validation of the results obtained different technical approaches and thus promote the early diagnosis and treatment of POCD.

Identification of a novel pro-inflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis

PubMed Central

LAGGNER, Ute; DI MEGLIO, Paola; PERERA, Gayathri K.; HUNDHAUSEN, Christian; LACY, Katie E.; ALI, Niwa; SMITH, Catherine H.; HAYDAY, Adrian C.; NICKOLOFF, Brian J.; NESTLE, Frank O.

2011-01-01

γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is poorly characterized. In this study we show in vivo evidence that human blood contains a distinct subset of pro-inflammatory cutaneous lymphocyte antigen (CLA) and C-C chemokine receptor (CCR) 6 positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of pro-inflammatory mediators including IL-17A and activated keratinocytes in a TNF-α and IFN-γ dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared to healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, this data indicates redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human pro-inflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease. PMID:21813772

Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.

PubMed Central

Balding, Joanna; Livingstone, Wendy J; Conroy, Judith; Mynett-Johnson, Lesley; Weir, Donald G; Mahmud, Nasir; Smith, Owen P

2004-01-01

The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear. PMID:15223609

Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation.

PubMed

Gadd, Victoria L; Patel, Preya J; Jose, Sara; Horsfall, Leigh; Powell, Elizabeth E; Irvine, Katharine M

2016-01-01

Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence. Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1) expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV) (n = 39) or non-alcoholic fatty liver disease (NAFLD) (n = 34) (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis) and healthy controls (n = 11) by flow cytometry. The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46%) of the decompensated patients who died within 8 months of recruitment. Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased susceptibility to infection in these patients.

Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.

PubMed

Alymova, Irina V; York, Ian A; McCullers, Jonathan A

2014-01-01

PB1-F2 protein, expressed from an alternative reading frame of most influenza A virus (IAV) PB1 segments, may possess specific residues associated with enhanced inflammation (L62, R75, R79, and L82) and cytotoxicity (I68, L69, and V70). These residues were shown to increase the pathogenicity of primary viral and secondary bacterial infections in a mouse model. In contrast to human seasonal influenza strains, virulence-associated residues are present in PB1-F2 proteins from pandemic H1N1 1918, H2N2 1957, and H3N2 1968, and highly pathogenic H5N1 strains, suggesting their contribution to viruses' pathogenic phenotypes. Non-human influenza strains may act as donors of virulent PB1-F2 proteins. Previously, avian influenza strains were identified as a potential source of inflammatory, but not cytotoxic, PB1-F2 residues. Here, we analyze the frequency of virulence-associated residues in PB1-F2 sequences from IAVs circulating in mammalian species in close contact with humans: pigs, horses, and dogs. All four inflammatory residues were found in PB1-F2 proteins from these viruses. Among cytotoxic residues, I68 was the most common and was especially prevalent in equine and canine IAVs. Historically, PB1-F2 from equine (about 75%) and canine (about 20%) IAVs were most likely to have combinations of the highest numbers of residues associated with inflammation and cytotoxicity, compared to about 7% of swine IAVs. Our analyses show that, in addition to birds, pigs, horses, and dogs are potentially important sources of pathogenic PB1-F2 variants. There is a need for surveillance of IAVs with genetic markers of virulence that may be emerging from these reservoirs in order to improve pandemic preparedness and response.

Acute Effects of Nitrate-Rich Beetroot Juice on Blood Pressure, Hemostasis and Vascular Inflammation Markers in Healthy Older Adults: A Randomized, Placebo-Controlled Crossover Study

PubMed Central

Raubenheimer, Kyle; Hickey, Danica; Leveritt, Michael; Fassett, Robert; Ortiz de Zevallos Munoz, Joaquin; Briskey, David; Kerr, Graham; Peake, Jonathan M.; Pecheniuk, Natalie M.

2017-01-01

Aging is associated with a vasoconstrictive, pro-coagulant, and pro-inflammatory profile of arteries and a decline in the bioavailability of the endothelium-derived molecule nitric oxide. Dietary nitrate elicits vasodilatory, anti-coagulant and anti-inflammatory effects in younger individuals, but little is known about whether these benefits are evident in older adults. We investigated the effects of 140 mL of nitrate-rich (HI-NI; containing 12.9 mmol nitrate) versus nitrate-depleted beetroot juice (LO-NI; containing ≤0.04 mmol nitrate) on blood pressure, blood coagulation, vascular inflammation markers, plasma nitrate and nitrite before, and 3 h and 6 h after ingestion in healthy older adults (five males, seven females, mean age: 64 years, age range: 57–71 years) in a randomized, placebo-controlled, crossover study. Plasma nitrate and nitrite increased 3 and 6 h after HI-NI ingestion (p < 0.05). Systolic, diastolic and mean arterial blood pressure decreased 3 h relative to baseline after HI-NI ingestion only (p < 0.05). The number of blood monocyte-platelet aggregates decreased 3 h after HI-NI intake (p < 0.05), indicating reduced platelet activation. The number of blood CD11b-expressing granulocytes decreased 3 h following HI-NI beetroot juice intake (p < 0.05), suggesting a shift toward an anti-adhesive granulocyte phenotype. Numbers of blood CD14++CD16+ intermediate monocyte subtypes slightly increased 6 h after HI-NI beetroot juice ingestion (p < 0.05), but the clinical implications of this response are currently unclear. These findings provide new evidence for the acute effects of nitrate-rich beetroot juice on circulating immune cells and platelets. Further long-term research is warranted to determine if these effects reduce the risk of developing hypertension and vascular inflammation with aging. PMID:29165355

The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial.

PubMed

Mena, Pedro; Tassotti, Michele; Martini, Daniela; Rosi, Alice; Brighenti, Furio; Del Rio, Daniele

2017-11-09

Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated. A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated. Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases. ClinicalTrials.gov, NCT03166540 . Registered on May 21, 2017.

Protein-enriched diet, with the use of lean red meat, combined with progressive resistance training enhances lean tissue mass and muscle strength and reduces circulating IL-6 concentrations in elderly women: a cluster randomized controlled trial.

PubMed

Daly, Robin M; O'Connell, Stella L; Mundell, Niamh L; Grimes, Carley A; Dunstan, David W; Nowson, Caryl A

2014-04-01

Physical inactivity, inadequate dietary protein, and low-grade systemic inflammation contribute to age-related muscle loss, impaired function, and disability. We assessed the effects of progressive resistance training (PRT) combined with a protein-enriched diet facilitated through lean red meat on lean tissue mass (LTM), muscle size, strength and function, circulating inflammatory markers, blood pressure, and lipids in elderly women. In a 4-mo cluster randomized controlled trial, 100 women aged 60-90 y who were residing in 15 retirement villages were allocated to receive PRT with lean red meat (∼160 g cooked) to be consumed 6 d/wk [resistance training plus lean red meat (RT+Meat) group; n = 53] or control PRT [1 serving pasta or rice/d; control resistance training (CRT) group; n = 47)]. All women undertook PRT 2 times/wk and received 1000 IU vitamin D3/d. The mean (± SD) protein intake was greater in the RT+Meat group than in the CRT group throughout the study (1.3 ± 0.3 compared with 1.1 ± 0.3 g · kg⁻¹ · d⁻¹, respectively; P < 0.05). The RT+Meat group experienced greater gains in total body LTM (0.45 kg; 95% CI: 0.07, 0.84 kg), leg LTM (0.22 kg; 95% CI: 0.02, 0.42 kg), and muscle strength (18%; 95% CI: 0.03, 0.34) than did the CRT group (all P < 0.05). The RT+Meat group also experienced a 10% greater increase in serum insulin-like growth factor I (P < 0.05) and a 16% greater reduction in the proinflammatory marker interleukin-6 (IL-6) (P < 0.05) after 4 mo. There were no between-group differences for the change in blood lipids or blood pressure. A protein-enriched diet equivalent to ∼1.3 g · kg⁻¹ · d⁻¹ achieved through lean red meat is safe and effective for enhancing the effects of PRT on LTM and muscle strength and reducing circulating IL-6 concentrations in elderly women. This trial was registered at the Australian Clinical Trials Registry as ACTRN12609000223235.

The Interplay Between Fiber and the Intestinal Microbiome in the Inflammatory Response12

PubMed Central

Kuo, Shiu-Ming

2013-01-01

Fiber intake is critical for optimal health. This review covers the anti-inflammatory roles of fibers using results from human epidemiological observations, clinical trials, and animal studies. Fiber has body weight–related anti-inflammatory activity. With its lower energy density, a diet high in fiber has been linked to lower body weight, alleviating obesity-induced chronic inflammation evidenced by reduced amounts of inflammatory markers in human and animal studies. Body weight–unrelated anti-inflammatory activity of fiber has also been extensively studied in animal models in which the type and amount of fiber intake can be closely monitored. Fermentable fructose-, glucose-, and galactose-based fibers as well as mixed fibers have shown systemic and local intestinal anti-inflammatory activities when plasma inflammatory markers and tissue inflammation were examined. Similar anti-inflammatory activities have also been demonstrated in some human studies that controlled total fiber intake. The anti-inflammatory activities of synbiotics (probiotics plus fiber) were reviewed as well, but there was no convincing evidence indicating higher efficacy of synbiotics compared with that of fiber alone. Adverse effects have not been observed with the amount of fiber intake or supplementation used in studies, although patients with Crohn’s disease may be more sensitive to inulin intake. Several possible mechanisms that may mediate the body weight–unrelated anti-inflammatory activity of fibers are discussed based on the in vitro and in vivo evidence. Fermentable fibers are known to affect the intestinal microbiome. The immunomodulatory role of the intestinal microbiome and/or microbial metabolites could contribute to the systemic and local anti-inflammatory activities of fibers. PMID:23319119

[The role of inflammation factors in development of acute coronary syndrome in patients with type 2 diabetes mellitus and impaired glucose tolerance].

PubMed

Chazova, T E; Masenko, V P; Zykov, K A; Golitsyna, T Iu

2007-01-01

To study the levels of inflammatory markers in acute coronary syndrome (ACS) and 6 months after its regression in patients with diabetes mellitus (DM) type 2; to evaluate effects of anxiodepressive disorders on inflammatory markers. The levels of high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-18 (IL-18), monocyte-chemmoattractant-protein-1 (MCP-1) and soluble vascular cell adhesion molecules (sVCAM) were measured in blood samples, severity of depressive symptoms and the level of glycated haemoglobin (HbA1c) were assessed in 58 patients with type 2 DM during ACS and in 54 patients 6 months after ACS regression. The levels of hsCRP and IL-18 correlate significantly with severity of myocardial lesion in ACS (p < 0.002; p < 0.009). Measurement of inflammatory markers 6 months after the discharge from hospital shows significant correlation between hsCRP, IL-18 and IL-6 levels; these levels were significantly lower in patients with HbA1c < 6.5% (tight glycemic control); there were associations between severity of depressive disorders and markers of inflammation (hsCRP, IL-18); analysis of MCP-1 and sVCAM levels 6 months after ACS regression shows a decrease of markers in 32-36% cases and an increase of markers in 64-67% cases. Complex immunological reactions, chronic hyperglycemia and depresssive disorders play an important role in development of latent inflammation of the vascular wall in patients with type 2 diabetes mellitus and ACS.

Airway purinergic responses in healthy, atopic nonasthmatic, and atopic asthmatic subjects exposed to ozone**

EPA Science Inventory

Context: Ozone exposure triggers airway inflammatory responses that maybe influenced bybiologically active purine metabolites. Objective:To examinethe relationships between airway purine metabolites and established inflammatory markers of ozone exposure, and to determine if thes...

Gender differences in fat distribution and inflammatory markers among Arabs.

PubMed

Farooq, Abdulaziz; Knez, Wade L; Knez, Kelly; Al-Noaimi, Asma; Grantham, Justin; Mohamed-Ali, Vidya

2013-01-01

Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n = 58) were matched for age, gender, and body mass index. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Women had more adipose tissue in the total abdominal (P = 0.04) and abdominal subcutaneous (P = 0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men.

Gender Differences in Fat Distribution and Inflammatory Markers among Arabs

PubMed Central

Farooq, Abdulaziz; Knez, Wade L.; Knez, Kelly; Al-Noaimi, Asma; Grantham, Justin; Mohamed-Ali, Vidya

2013-01-01

Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). Objective. To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n = 58) were matched for age, gender, and body mass index. Methods. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Results. Women had more adipose tissue in the total abdominal (P = 0.04) and abdominal subcutaneous (P = 0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. Conclusion. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men. PMID:24227909

Calcitriol Prevents Cardiovascular Repercussions in Puromycin Aminonucleoside-Induced Nephrotic Syndrome

PubMed Central

Roberto, Roncon-Albuquerque

2018-01-01

Puromycin aminonucleoside-induced nephrotic syndrome (PAN-NS) is characterized by cardiac remodeling and increased local inflammatory activity. Patients with NS and animal models of NS have vitamin D3 deficiency. The aim of the present study was to evaluate the influence of calcitriol on cardiac remodeling and local inflammatory state in PAN-NS rat model. Male Sprague-Dawley rats were injected with PAN or vehicle on day 0. PAN and control rats were divided into two subgroups for the administration of calcitriol (PAN-D and Ct-D groups) or the vehicle (PAN-V and Ct-V groups) during 21 days. On day 21, the renal function, metabolic balance, calcitriol and FGF-23 plasma levels, prohypertrophy and proinflammatory markers (ET-1, TGF-β1, TNF-α, and IL-1β), and calcium signaling molecules (PLB and SERCA-2a) were evaluated. Twenty-one days after injection, PAN-V group presented cardiac hypertrophy and a modulation of proinflammatory markers local expression. Calcitriol treatment of PAN rats prevented cardiac hypertrophy and was associated with marked reduction in the cardiac expression levels of proinflammatory markers. Our results suggest that vitamin D3 deficiency in PAN-NS may contribute to cardiac remodeling and to the increase in local inflammatory activity. Calcitriol treatment prevents both cardiac repercussions and local inflammatory processes in PAN-NS. PMID:29607318

Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects

PubMed Central

Coccaro, Emil F.; Lee, Royce; Fanning, Jennifer R.; Fuchs, Dietmar; Goiny, Michel; Erhardt, Sophie; Christensen, Kyle; Brundin, Lena; Coussons-Read, Mary

2017-01-01

Inflammatory proteins are thought to be causally involved in the generation of aggression, possibly due to direct effects of cytokines in the central nervous system and/or by generation of inflammatory metabolites along the tryptophan-kynurenine (TRP/KYN) pathway, including KYN and its active metabolites kynurenic acid (KA), quinolinic acid (QA), and picolinic acid (PA). We examined plasma levels of TRP, KYN, KA, QA, and PA in 172 medication-free, medically healthy, human subjects to determine if plasma levels of these substances are altered as a function of trait aggression, and if they correlate with current plasma levels of inflammatory markers. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble interleukin-1 receptor-II (sIL-1RII) protein were also available in these subjects. We found normal levels of TRP but reduced plasma levels of KYN (by 48%), QA (by 6%), and a QA/KA (by 5%) ratio in subjects with Intermittent Explosive Disorder (IED) compared to healthy controls and psychiatric controls. Moreover, the metabolites were not associated with any of the inflammatory markers studied. These data do not support the hypothesis that elevated levels of KYN metabolites would be present in plasma of subjects with IED, and associated with plasma inflammation. However, our data do point to a dysregulation of the KYN pathway metabolites in these subjects. Further work will be necessary to replicate these findings and to understand their role in inflammation and aggression in these subjects. PMID:27318828

Circulating microRNA are predictive of aging and acute adaptive response to resistance exercise in men

USDA-ARS?s Scientific Manuscript database

Circulating microRNA (c-miRNA) have the potential to function as novel noninvasive markers of the underlying physiological state of skeletal muscle. This investigation sought to determine the influence of aging on c-miRNA expression at rest and following resistance exercise in male volunteers (Young...

The role of a dairy fraction rich in milk fat globule membrane in the suppression of postprandial inflammatory markers and bone turnover in obese and overweight adults: an exploratory study.

PubMed

Rogers, Tara S; Demmer, Elieke; Rivera, Nancy; Gertz, Erik R; German, J Bruce; Smilowitz, Jennifer T; Zivkovic, Angela M; Van Loan, Marta D

2017-01-01

Inflammation is associated with increased bone resorption; the role of inflammation in postprandial bone turnover has not been explored. Consumption of milk fat globule membrane (MFGM) reduces inflammation in animal models. This study aimed to measure postprandial changes in bone turnover after intake of high saturated fat test meals, with- and without the anti-inflammatory ingredient MFGM. Subjects ( n  = 36 adults) were obese (BMI 30-39.9 kg/m 2 ) or overweight (BMI 25-29.9 kg/m 2 ) with two traits of Metabolic Syndrome. Subjects consumed a different test meal on four occasions at random; blood draws were taken at baseline and 1, 3, and 6 h postprandial. Test meals included whipping cream (WC), WC + MFGM, palm oil (PO) and PO + MFGM. Biomarkers of bone turnover and inflammation were analyzed from all four time points. Test meal (treatment) by time interactions were significant for bone resorption marker C-telopeptide of type 1 collagen (CTX) ( p  < 0.0001) and inflammatory marker interleukin 10 (IL-10) ( p  = 0.012). Significant differences in overall postprandial response among test meals were found for CTX and soluble intercellular adhesion molecule (sICAM), with the greatest overall postprandial suppression of CTX occurring in meals containing MFGM. However, test meal by MFGM interactions were non- significant for bone and inflammatory markers. Correlations between CTX and inflammatory markers were non-significant. This exploratory analysis advances the study of postprandial suppression of bone turnover by demonstrating differing effects of high SFA meals that contained MFGM; however MFGM alone did not directly moderate the difference in postprandial CTX response among test meals in this analysis. These observations may be useful for identifying foods and ingredients which maximize the suppression of bone resorption, and for generating hypotheses to test in future studies examining the role of inflammation in postprandial bone turnover. Clinicaltrials.gov NCT01811329. Registered 11 March 2013.

Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

USDA-ARS?s Scientific Manuscript database

Background. Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately des...

Hemostatic, inflammatory, and oxidative markers in pesticide user farmers.

PubMed

Madani, Fatima Zohra; Hafida, Merzouk; Merzouk, Sid Ahmed; Loukidi, Bouchra; Taouli, Katia; Narce, Michel

2016-01-01

The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vitamins C and E, glutathione, catalase, and superoxide dismutase activities in farmers. Serum C-reactive protein, prothrombin, and fibrinogen levels were enhanced in these farmers. In conclusion, inflammation, oxidative stress, and metabolic perturbations reflected the possibility of the effects of pesticides to farmers.

Effect of Leisure Activities on Inflammation and Cognitive Function in an Aging Sample

PubMed Central

Friedman, Elliot; Quinn, Jill; Chen, Ding-Geng (Din); Mapstone, Mark

2012-01-01

Cardiovascular disease risk factors (CVDRFs) increase the risk of dementia. The purpose of this study was to examine whether leisure activities (mental, physical, and social activities) modified the effect of CVDRFs on inflammatory markers and cognitive function in middle and old age. A secondary-data analysis study was conducted using data from 405 middle-age participants (40 –59 years) and 342 old-age participants (60 – 84 years) who participated in the Survey of Midlife Development in the United States. CVDRFs were obtained from a combination of self-report medical history and blood-based biomarkers. Three CVDRF groups (≤1, 2, and ≥3 CVDRFs) were identified. More CVDRFs were significantly associated with higher levels of inflammatory markers in both age groups, and associated with lower levels of executive function in the old age group. CVDRFs were not related to the frequency of leisure activities in either age group. After controlling for covariates, higher levels of physical activities were significantly associated with lower levels of inflammatory markers, and higher levels of mental activities were associated with higher levels of cognitive function. In the old age group, physical activities also moderated the effect of CVDRFs on episodic memory, and mental activities moderated the effect of CVDRFs on interleukin-6. Multiple CVDRFs may be associated with poorer cognitive function and higher inflammatory markers, but middle-age and older adults with CVDRFs may not engage in frequent physical and cognitive activities that may be protective. It is important to develop strategies to facilitate engagement in these activities from midlife. PMID:22377120

[Association between inflammatory markers and microbial translocation in patients with human immunodeficiency virus infection taking antiretroviral treatment].

PubMed

Reus Bañuls, Sergio; Portilla Sogorb, Joaquín; Sanchez-Paya, José; Boix Martínez, Vicente; Giner Oncina, Livia; Frances, Rubén; Such, José; Merino Lucas, Esperanza; Gimeno Gascón, Adelina

2014-01-21

Inflammatory biomarkers are increased in patients with human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART) improves some parameters but do not normalize them. The aim of this study is to determine those factors (including microbial translocation) associated with higher inflammation in HIV treated patients. Transversal observational study. HIV patients receiving ART with an HIV viral load (VL)<400 copies/mL. Selection of patients: consecutively between November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). Main explanatory variable: microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6 or TNF-α levels above percentile 75 (group 1) were compared with the rest of patients (group 2). Odds ratio (OR) were determined. Eighty-one patients were included (73% male, median age 45 years, 48% stage C). Twenty-six percent had chronic hepatitis C. Median CD4 cell was 493/mm(3) and 30% had detectable HIV VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77, P<.0001), sCD14 levels (P<.0001) and history of cardiovascular disease (OR 15, P<.01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR 62, P<.0001) and previous cardiovascular disease (OR 25, P<.01). In patients with HIV infection receiving treatment, the higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events. Copyright © 2013 Elsevier España, S.L. All rights reserved.