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Sample records for inflammatory response syndrome

  1. Homocysteine in dogs with systemic inflammatory response syndrome.

    PubMed

    Patterson, B E; Barr, J W; Fosgate, G T; Berghoff, N; Steiner, J M; Suchodolski, J S; Black, D M

    2013-12-01

    To compare serum concentrations of homocysteine in healthy dogs and those fitting the criteria for systemic inflammatory response syndrome and to compare these values to commonly measured B-vitamins. Study dogs were classified into non-infectious systemic inflammatory response syndrome or sepsis groups and blood was drawn on Day 1 of the patient's hospitalisation for measurement of serum homocysteine, folate and cobalamin concentrations. Homocysteine concentration was measured in 51 clinically healthy dogs to serve as the control group. A statistically significant difference was found between the homocysteine concentrations of the healthy group when compared to non-infectious systemic inflammatory response syndrome and sepsis groups. Homocysteine values were not correlated with folate, cobalamin or APPLEfast severity scores. Homocysteine concentrations were significantly lower in sick dogs when compared to the control group, which is dissimilar to the human population. The clinical significance of homocysteine changes in critically ill dogs is currently unknown. © 2013 British Small Animal Veterinary Association.

  2. [Systemic inflammatory response syndrome (SIRS) and endothelial cell injury].

    PubMed

    Gando, Satoshi

    2004-12-01

    During recent years, evidences have been accumulated demonstrating bidirectional crosstalk between coagulation and inflammation. This review outlines the influences that coagulation and inflammation exert on each other to the endothelium and how these systems induce systemic inflammatory response syndrome (SIRS). Then we discussed the implications of leucocyte-endothelial activation to endothelial cell injury followed by multiple organ dysfunction syndrome (MODS) in patients with sustained SIRS. Last we demonstrated an important role of inflammatory circulation disturbance induced by endothelial cell injury for the pathogenesis of MODS in SIRS and sepsis.

  3. Systemic inflammatory response syndrome after cardiac operations.

    PubMed

    Cremer, J; Martin, M; Redl, H; Bahrami, S; Abraham, C; Graeter, T; Haverich, A; Schlag, G; Borst, H G

    1996-06-01

    A systemic inflammatory response after open heart operation may be responsible for hyperdynamic circulatory instability and organ dysfunction. To what extent mediator release is involved needs to be clarified. Ten patients with postoperative hyperdynamic circulatory dysregulation (group I) requiring application of alpha-constrictors and 10 patients with routine cardiac procedures and stable postoperative hemodynamic indices (group II) were analyzed for mediator release and metabolic and hemodynamic changes until the third postoperative day. Group I patients showed a significantly increased cardiac index and decreased systemic vascular resistance after bypass (cardiac index, group I: 5.2 +/- 1.2 L.min-1.m-2, group II: 2.5 +/- 1.6 L.min-1.m-2; systemic vascular resistance, group I: 495 +/- 204 dyne.s. cm-5, group II: 1,356 +/- 466 dyne.s.cm-5) and at 3 hours (cardiac index, group I: 4.4 +/- 0.8 L.min-1.m-2, group II: 2.9 +/- 0.6 L.min-1.m-2; systemic vascular resistance, group I: 567 +/- 211 dyne.s.cm-5, group II: 1,053 +/- 273 dyne.s.cm-5). Significantly higher serum levels of interleukin-6 were assessed in group I (postbypass, group I: 6,812 +/- 9,293 pg/mL, group II: 295 +/- 303 pg/mL; 3 hours, group I: 3,474 +/- 5,594 pg/mL, group II: 286 +/- 296 pg/mL). Concentrations of elastase, tumor necrosis factor, soluble tumor necrosis factor receptor, and interleukin-8 were elevated in group I (not significant). Early postoperative levels of soluble E-selectin and soluble intercellular adhesion molecule were also higher in group I (not significant). Continuously increased levels of endotoxin could be detected in only 3 of 10 patients in group I. Severe lactic acidosis (> or = 5 mmol/L) occurred in group I only. Postoperative hyperdynamic instability after open heart operations appears to be associated with a certain pattern of mediator release. In particular, interleukin-6 appears to be involved in circulatory dysregulation and metabolic derangement.

  4. Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy.

    PubMed

    Matsuda, Naoyuki; Hattori, Yuichi

    2006-07-01

    In recent years, extensive basic science research has led to a clear understanding of the molecular mechanisms contributing to the pathophysiology of sepsis. Sepsis is now defined as a systemic inflammatory response syndrome (SIRS) in which there is an identifiable focus of infection. SIRS can be also precipitated by non-infective events such as trauma, pancreatitis, and surgery. As a consequence of an overactive SIRS response, the function of various organ systems may be compromised, resulting in multiple organ dysfunction syndrome (MODS) and death. Production and activation of multiple proinflammatory genes are likely to play a key role in the pathogenesis of MODS development. This review article focuses on the molecular mechanisms and components involved in the pathogenesis of severe sepsis. This includes cellular targets of sepsis-inducing bacterial products and their signaling pathways with a major emphasis on transcription factors and new therapeutic approaches to severe sepsis.

  5. The Transcriptome of the Fetal Inflammatory Response Syndrome

    PubMed Central

    Madsen-Bouterse, Sally A.; Romero, Roberto; Tarca, Adi L.; Kusanovic, Juan Pedro.; Espinoza, Jimmy; Kim, Chong Jai; Kim, Jung-Sun; Edwin, Samuel S.; Gomez, Ricardo; Draghici, Sorin

    2012-01-01

    Problem The fetal inflammatory response syndrome (FIRS) is considered the counterpart of the systemic inflammatory response syndrome (SIRS), but similarities in their regulatory mechanisms are unclear. This study characterizes the fetal mRNA transcriptome of peripheral leukocytes to identify key biological processes and pathways involved in FIRS. Method of Study Umbilical cord blood from preterm neonates with FIRS (funisitis, plasma IL-6>11 pg/ml; n=10) and neonates with no evidence of inflammation (n=10) was collected at birth. Results Microarray analysis of leukocyte RNA revealed differential expression of 541 unique genes, changes confirmed by qRT-PCR for 41 or of 44 genes tested. Similar to SIRS and sepsis, ontological and pathway analyses yielded significant enrichment of biological processes including antigen processing and presentation, immune response, and processes critical to cellular metabolism. Results are comparable with microarray studies of endotoxin challenge models and pediatric sepsis, identifying 25 genes across all studies. Conclusions This study is the first to profile genome-wide expression in FIRS, which demonstrates a substantial degree of similarity with SIRS despite differences in fetal and adult immune systems. PMID:20059468

  6. Methylation metabolism in sepsis and systemic inflammatory response syndrome.

    PubMed

    Semmler, Alexander; Prost, Jean-Christophe; Smulders, Yvo; Smith, Desiree; Blom, Henk; Bigler, Laurent; Linnebank, Michael

    2013-08-01

    We have recently shown that sepsis leads to alterations of methylation metabolism in a rodent model. In this study we analyzed methylation metabolism and DNA methylation in human sepsis. Patients treated in one of the Intensive Care Units (ICU) at the University Hospital Bonn diagnosed with sepsis or systemic inflammatory response syndrome (n = 12) and patients who were treated due to traumatic brain injury, or stroke without clinical or laboratory signs of sepsis or major inflammation (n = 22) were included. Blood samples were taken two times a week, until ICU treatment was discontinued. Deproteinized plasma was used for simultaneous determination of the ubiquitous methyl-group donor S-adenosylmethionine (SAM) and its demethylated residue, S-adenosylhomocysteine (SAH), by using stable isotope dilution tandem mass spectrometry. Homocysteine (Hcys), hydrolyzation product of SAH, was determined by fully automated particle-enhanced immunonephelometry, and global DNA-methylation was measured by liquid chromatography tandem mass spectrometry. SAM (p < 0.001) and SAH (p < 0.001) plasma levels were higher in septic patients suggesting an increased cellular release of SAM and SAH in septic patients. The SAM/SAH ratio was decreased in septic patients (p = 0.002). There were no differences in homocysteine plasma levels (p = 0.32) or global leukocyte DNA methylation between septic and non-septic patients (p = 0.21) suggesting that sepsis-induced changes in methylation metabolism do not affect homocysteine plasma levels or the availability of SAM-derived methyl groups for DNA methylation. Sepsis and systemic inflammatory response syndrome induce considerable changes of methylation metabolism without apparent functional consequences on homocysteine plasma levels or DNA methylation. Further studies may explore the clinical relevance of the observed changes.

  7. Predictors of systemic inflammatory response syndrome following percutaneous nephrolithotomy

    PubMed Central

    Ramaraju, Karunamoorthy; Paranjothi, Arun Kumar; Namperumalsamy, Dhinakar Babu; Chennakrishnan, Ilamparuthi

    2016-01-01

    Introduction and Objectives: Sepsis remains one of the dreaded complications of percutaneous nephrolithotomy (PCNL). To analyze prospectively the preoperative and intraoperative factors that predict the occurrence of systemic inflammatory response syndrome (SIRS) in patients undergoing PCNL so that we can aggressively manage those patients from the preoperative period itself and avert the dangerous complications. Materials and Methods: A prospective study was carried out between August 2012 and March 2013 including all patients who underwent PCNL. Patients with infected collecting system, synchronous ureteric stones, stents, or percutaneous nephrostomy drainage were excluded from the study. Patients were evaluated with physical examination, urine analysis, urine culture and sensitivity, complete blood count, renal function test, X-ray kidney, ureter, and bladder (KUB), and plain and contrast-enhanced computerized tomography KUB. Patients who developed any two or above of the following in the postoperative period were considered to have developed SIRS. (1) Temperature >100.4°F (38°C) or <96.8°F (36°C). (2) Pulse rate >90/min. (3) Respiratory rate >20/min. (4) White blood cell count >12,000/ml or <4000/ml. Results: Of the 120 patients who underwent PCNL 29 (24.1%) developed features of SIRS. On univariate analysis, gender, diabetes mellitus, bladder urine culture, and serum creatinine were found to be statistically insignificant. Blood transfusion (P = 0.009), no of access tracts (P = 0.001), pelvic urine culture (P = 0.04), stone culture (P = 0.003), stone size (P = 0.001), age (P = 0.019), and operative time (P = 0.004) were found to be statistically significant. On multivariate regression analysis stone size, no of access tracts, operative time, and stone culture were found to be statistically significant with regard to the occurrence of SIRS. Conclusion: Patients with above-identified risk factors must be aggressively treated to prevent the occurrence of

  8. Systemic inflammatory response syndrome criteria in defining severe sepsis.

    PubMed

    Kaukonen, Kirsi-Maija; Bailey, Michael; Pilcher, David; Cooper, D Jamie; Bellomo, Rinaldo

    2015-04-23

    The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach. We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria. Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis. Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without any transitional increase in risk at a threshold of two SIRS criteria. The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in

  9. Cell surface adrenergic receptor stimulation modifies the endothelial response to SIRS. Systemic Inflammatory Response Syndrome.

    PubMed

    Tighe, D; Moss, R; Bennett, D

    1996-11-01

    The complex pathway seen in patients with the systemic inflammatory response syndrome (SIRS) does not readily respond to mediator blockade. All such trials conducted in SIRS patients have shown no benefit in reducing mortality. We have shown experimentally that in sepsis, the administration of beta 2-adrenoceptor agonists reduces hepatic cellular injury, whereas administration of an alpha 1-adrenoceptor agonist increases hepatic cellular injury. Inflammatory mediators can cause a dose-related reversible change in target endothelial cells (ECs). There is a substantial body of literature describing the anti-inflammatory effects of beta 2-adrenoceptor agonists. They reduce both the increased permeability and the production of inflammatory mediators from ECs. Cellular transduction processes are involved when adrenergic receptor agonists modify either the anti-inflammatory or proinflammatory response to sepsis in ECs. Inflammatory mediators and alpha 1-adrenoceptor agonists stimulate their trimeric G protein-linked receptors to produce diacylglycerol (DAG) and increase the intracellular concentration of calcium. DAG is involved in the production of both inflammatory proteins and lipids. In addition, mitogen-activated protein kinase (MAPK) is activated which is also involved in the production of inflammatory proteins and lipids. beta 2-adrenoceptor agonists activate their trimeric G protein-linked receptors to produce the stimulatory G protein (Gs). Gs stimulates adenyl cyclase to form cyclic adenosine monophosphate (cAMP) and activate protein kinase A (PKA). PKA is involved in activating gene transcription agents to produce anti-inflammatory proteins such as interleukin-10. PKA also inhibits phospholipase C and MAPK. Although promising, the use of beta-adrenoceptor agonists or agonists that increase cellular cAMP to activate the cells' endogenous anti-inflammatory pathway requires further study.

  10. Systemic inflammatory response syndrome criteria and the prediction of hospital mortality in critically ill patients: a retrospective cohort study.

    PubMed

    Taniguchi, Leandro Utino; Pires, Ellen Maria Campos; Vieira, José Mauro; Azevedo, Luciano Cesar Pontes de

    2017-09-28

    This study intended to determine whether the systemic inflammatory response syndrome criteria can predict hospital mortality in a Brazilian cohort of critically ill patients. We performed a retrospective cohort study at a private tertiary hospital in São Paulo (SP), Brazil. We extracted information from the adult intensive care unit database (Sistema EpimedTM). We compared the SAPS 3 and the systemic inflammatory response syndrome model as dichotomous (≥ 2 criteria: systemic inflammatory response syndrome -positive versus 0 - 1 criterion: systemic inflammatory response syndrome -negative) and ordinal variables from 0 to 4 (according to the number of systemic inflammatory response syndrome criteria met) in the prediction of hospital mortality at intensive care unit admission. Model discrimination was compared using the area under the receiver operating characteristics (AUROC) curve. From January to December 2012, we studied 932 patients (60.4% were systemic inflammatory response syndrome -positive). systemic inflammatory response syndrome -positive patients were more critically ill than systemic inflammatory response syndrome -negative patients and had higher hospital mortality (16.9% versus 8.1%, p < 0.001). In the adjusted analysis, being systemic inflammatory response syndrome -positive independently increased the risk of death by 82% (odds ratio 1.82; 95% confidence interval [CI] 1.12 - 2.96, p = 0.016). However, the AUROC curve for the SAPS 3 model was higher (0.81, 95%CI 0.78 - 0.85) compared to the systemic inflammatory response syndrome model with the systemic inflammatory response syndrome criteria as a dichotomous variable (0.60, 95%CI 0.55 - 0.65) and as an ordinal variable (0.62, 95%CI 0.57 - 0.68; p < 0.001) for hospital mortality. Although systemic inflammatory response syndrome is associated with hospital mortality, the systemic inflammatory response syndrome criteria show low accuracy in the prediction of mortality compared with the SAPS 3.

  11. [SIRS (systemic inflammatory response syndrome): clinical entity, definitions, and the significance].

    PubMed

    Kushimoto, S; Yamamoto, Y

    1999-01-01

    The clinical entity, definitions, and the significance of SIRS (systemic inflammatory response syndrome) were reviewed. The term, SIRS was proposed to define sepsis and its sequelae clearly in 1991, in order to make early detection of the disease possible, and to improve the ability to compare innovative potential diagnostic and therapeutic modalities by standardizing terms. Although the criteria of SIRS is not strict and too sensitive, SIRS has been shown to be useful as a warning sign of severe condition in clinical setting. We also discussed about a new concept, CARS (compensatory anti-inflammatory response syndrome), which was characterized as anti-inflammatory mediators-dominant condition, in this issue.

  12. ADAMTS-13 in Critically Ill Patients With Septic Syndromes and Noninfectious Systemic Inflammatory Response Syndrome.

    PubMed

    Aibar, Jesús; Castro, Pedro; Espinosa, Gerard; Fernández, Sara; Hernández, Cristina; Rinaudo, Mariano; Butjosa, Montserrat; Tàssies, Dolors; Reverter, Joan Carles; Nicolás, Josep Maria

    2015-06-01

    Decreased ADAMTS-13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) seems to be associated with a poor prognosis in sepsis. However, its role in different septic syndromes and other causes of systemic inflammatory response syndrome (SIRS) remains unclear. The aims of this study were to assess ADAMTS-13 levels in patients with septic syndromes or noninfectious SIRS and to determine their association with morbidity and mortality. The study population consisted of 178 patients admitted to the medical intensive care unit presenting either septic syndromes or noninfectious SIRS. ADAMTS-13 levels were analyzed. Patients with septic syndromes showed significantly lower levels of ADAMTS-13 compared with those with noninfectious SIRS (P = 0.014). Patients with severe sepsis or septic shock presented lower levels than those of patients with sepsis (P = 0.086). A significant negative correlation was found between ADAMTS-13 levels and delta Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores at admission in the septic patients. Patients who died had significantly lower levels of ADAMTS-13 compared with survivors, both in the whole population and among the septic patients (P = 0.002 and P = 0.009, respectively). Logistic regression analysis showed that decreased ADAMTS-13 levels were associated with an increased risk of in-intensive care unit mortality (odds ratio, 0.985; 95% confidence interval, 0.973-0.998; P = 0.023). Septic patients have lower levels of ADAMTS-13 than do patients with noninfectious SIRS. Levels of ADAMTS-13 are correlated with illness severity in patients with septic syndromes. ADAMTS-13 levels were associated with an increased risk of mortality in critically ill patients with SIRS especially those with septic syndromes.

  13. An Algorithm for Systemic Inflammatory Response Syndrome Criteria-Based Prediction of Sepsis in a Polytrauma Cohort.

    PubMed

    Lindner, Holger A; Balaban, Ümniye; Sturm, Timo; Weiß, Christel; Thiel, Manfred; Schneider-Lindner, Verena

    2016-12-01

    Lifesaving early distinction of infectious systemic inflammatory response syndrome, known as "sepsis," from noninfectious systemic inflammatory response syndrome is challenging in the ICU because of high systemic inflammatory response syndrome prevalence and lack of specific biomarkers. The purpose of this study was to use an automatic algorithm to detect systemic inflammatory response syndrome criteria (tachycardia, tachypnea, leukocytosis, and fever) in surgical ICU patients for ICU-wide systemic inflammatory response syndrome prevalence determination and evaluation of algorithm-derived systemic inflammatory response syndrome descriptors for sepsis prediction and diagnosis in a polytrauma cohort. Cross-sectional descriptive study and retrospective cohort study. Electronic medical records of a tertiary care center's surgical ICU, 2006-2011. All ICU admissions and consecutive polytrauma admissions. None. Average prevalence of conventional systemic inflammatory response syndrome (≥ 2 criteria met concomitantly) from cross-sectional application of the algorithm to all ICU patients and each minute of the study period was 43.3%. Of 256 validated polytrauma patients, 85 developed sepsis (33.2%). Three systemic inflammatory response syndrome descriptors summarized the 24 hours after admission and before therapy initiation: 1) systemic inflammatory response syndrome criteria average for systemic inflammatory response syndrome quantification over time, 2) first-to-last minute difference for trend detection, and 3) change count reflecting systemic inflammatory response syndrome criteria fluctuation. Conventional systemic inflammatory response syndrome for greater than or equal to 1 minute had 91% sensitivity and 19% specificity, whereas a systemic inflammatory response syndrome criteria average cutoff value of 1.72 had 51% sensitivity and 77% specificity for sepsis prediction. For sepsis diagnosis, systemic inflammatory response syndrome criteria average and first

  14. [Auto-inflammatory syndromes].

    PubMed

    Grateau, Gilles

    2005-02-28

    Auto-inflammatory syndromes are a group of hereditary diseases characterised by intermittent bouts of clinical inflammation with focal organ involvement mainly: abdomen, musculoskeletal system and skin. The most frequent is familial Mediterranean fever, which affects patients of Mediterranean descent all over the world. Three other types have been recently clinically as well as genetically characterised. A thorough diagnosis is warranted, as clinical and therapeutic management is specific for each of these diseases, as underlied by a specific inflammatory pathway. This new group of diseases has already opened new avenues in our understanding of the inflammatory response.

  15. [The systemic inflammatory response syndrome correction in acute destructive pancreatitis].

    PubMed

    Agapov, M A; Khoreva, M V; Gorskiĭ, V A

    2011-01-01

    Acute pancreatitis is a disease of variable severity. In which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis. In our research we have estimated influence of not steroid anti-inflammatory preparation on synthesis pro-and anti-inflammatory Cytokines at healthy donors and at patients with Acute pancreatitis.

  16. Staphylococcus pseudintermedius infection associated with nodular skin lesions and systemic inflammatory response syndrome in a dog.

    PubMed

    Min, Sa-Hee; Kang, Min-Hee; Sur, Jung-Hyang; Park, Hee-Myung

    2014-05-01

    A 10-year-old Pekingese dog with atopic dermatitis was referred due to pyrexia, multiple skin nodules, anorexia, and depression. The dog was diagnosed as having systemic inflammatory response syndrome (SIRS) induced by bacterial dermatitis. This case presents diagnosis and treatment of SIRS with staphylococcal skin infection in a dog that was immunosuppressed due to long-term use of corticosteroid.

  17. Peripheral hemophagocytosis: An early indicator of advanced systemic inflammatory response syndrome/hemophagocytic syndrome.

    PubMed

    Kuwata, Kazuhisa; Yamada, Shoko; Kinuwaki, Etsuo; Naito, Makoto; Mitsuya, Hiroaki

    2006-04-01

    Peripheral hemophagocytosis (PHP) is seen in patients with hemophagocytic syndrome (HPS), a clinical status in which activated macrophages play a role in its pathogenesis. The inflammatory state, systemic inflammatory response syndrome (SIRS), is also associated with activated macrophages. However, the link between HPS and SIRS and the clinical implications of PHP remain to be determined. In the present work, we examined the clinical utility and impact of the detection of PHP and the link between HPS and SIRS. We studied the clinical and laboratory profiles of 322 SIRS patients (174 men; mean age, 68 +/- 22 years; range, 16-99 years) who visited an urban hospital specializing in respiratory, cardiovascular, digestive, renal diseases, general surgery, and orthopedics in Japan. Peripheral hemophagocytosis was detected in 40 (23 men; mean age, 81.3 +/- 8.7 years; range, 63-98 years) of 322 patients on 3 +/- 2 days after SIRS diagnosis as determined with a "blunt-edged-smear" method differing from the conventional "feather-edged smear" method. The incidence of advanced SIRS and ensuing death in the SIRS+ PHP- group (37 and 21 of 40, respectively) was significantly greater than in the SIRS+ PHP- group (82 and 17 of 282) (P < 0.01). The duration from SIRS diagnosis to recovery in 19 SIRS+ PHP- surviving patients (26 +/- 18 days) was longer than that in 19 age-matched SIRS+ PHP- surviving patients who initially presented comparable clinical profiles (6 +/- 3 days) (P < 0.001). Bone marrow analysis in all 7 patients having PHP and SIRS showed no HPS initially (<3% hemophagocytes), but all subsequently developed HPS at 7 +/- 1 days after the diagnosis, confirmed by the presence of 9% +/- 13% hemophagocytes in the bone marrow. Electron microscopic and immunohistochemical analyses revealed that PHP was derived from hemophagocytes in the bone marrow. The present data strongly suggest that PHP detection could serve as an early indicator for advanced SIRS and/or HPS and that the

  18. Systemic inflammatory response syndrome (SIRS): where did it come from and is it still relevant today?

    PubMed

    Balk, Robert A

    2014-01-01

    The concept of a systemic inflammatory response syndrome (SIRS) to describe the complex pathophysiologic response to an insult such as infection, trauma, burns, pancreatitis, or a variety of other injuries came from a 1991 consensus conference charged with the task of developing an easy-to-apply set of clinical parameters to aid in the early identification of potential candidates to enter into clinical trials to evaluate new treatments for sepsis. There was recognition that a diverse group of injuries produced a common inflammatory response in the host and provided attractive targets for new anti-inflammatory molecules designed to prevent further propagation and/or provide specific treatment. Effective application of these new anti-inflammatory strategies necessitated identification of early clinical markers that could be assessed in real-time and were likely to define a population of patients that would have a beneficial response to the targeted intervention. It was felt that early clinical manifestations might be more readily available to clinicians than more sophisticated and specific assays for inflammatory substances that were systemically released by the network of injurious inflammatory events. Therefore, the early definition of a systemic inflammatory response syndrome (SIRS) was built upon a foundation of basic clinical and laboratory abnormalities that were readily available in almost all clinical settings. With further refinement, it was hoped, that this definition would have a high degree of sensitivity, coupled with a reasonable degree of specificity. This manuscript reviews the derivation, application, utilization, potential benefits, and speculation regarding the future of the SIRS definition.

  19. The biochemical origin of pain: the origin of all pain is inflammation and the inflammatory response. Part 2 of 3 - inflammatory profile of pain syndromes.

    PubMed

    Omoigui, Sota

    2007-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby briefly describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome/reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and serve as a foundation to be built upon by other researchers and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain

  20. Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions.

    PubMed

    Takei, Miwa; Kobayashi, Makiko; Herndon, David N; Pollard, Richard B; Suzuki, Fujio

    2006-09-01

    In association with the systemic inflammatory response syndrome (SIRS), anti-inflammatory response syndrome is commonly manifested in patients with trauma, burn injury, and after major surgery. These patients are increasingly susceptible to infection with various pathogens due to the excessive release of anti-inflammatory cytokines from anti-inflammatory effector cells. Recently, CC-chemokine ligand 2 (CCL2) found in the sera of mice with pancreatitis was identified as an active molecule for SIRS-associated anti-inflammatory response manifestation. Also, the inhibitory activity of glycyrrhizin (GL) on CCL2 production was reported. Therefore, the effect of GL on SIRS-associated anti-inflammatory response manifestation was investigated in a murine SIRS model. Without any stimulation, splenic T cells from mice 5 days after SIRS induction produced cytokines associated with anti-inflammatory response manifestation. However, these cytokines were not produced by splenic T cells from SIRS mice previously treated with GL. In dual-chamber transwells, IL-4-producing cells were generated from normal T cells cultured with peripheral blood polymorphonuclear neutrophils (PMN) from SIRS mice. However, IL-4-producing cells were not generated from normal T cells in transwell cultures performed with PMN from GL-treated SIRS mice. CCL2 was produced by PMN from SIRS mice, while this chemokine was not demonstrated in cultures of PMN from SIRS mice treated with GL. These results indicate that GL has the capacity to suppress SIRS-associated anti-inflammatory response manifestation through the inhibition of CCL2 production by PMN.

  1. Coagulation response in dogs with and without systemic inflammatory response syndrome - preliminary results.

    PubMed

    Bauer, Natali; Moritz, Andreas

    2013-02-01

    The impact of systemic inflammatory response syndrome (SIRS) on all phases of coagulation is largely unknown in dogs. Fifty-six healthy dogs (controls) and 25 diseased dogs were included. Based on physical and hematological examination, dogs were classified as "no-SIRS" (n=7) or "SIRS" (n=18). Evaluated coagulation variables included platelets, coagulation times, fibrinogen, antithrombin (AT), FVIII, protein C, protein S, activated protein C (APC)-ratio, calculated from aPTT with and without presence of APC, and kaolin-activated thrombelastography (TEG). Overall, no-SIRS and SIRS were characterized by hypocoaguable state (P<0.001 compared to controls) i.e., prolonged coagulation times, decreased AT (median 59 U/L and 89 U/L versus 126 U/L), and FVIII (median 19 U/L and 70 U/L versus 102 U/L). In no-SIRS and SIRS, APC-ratio was significantly lower than in the controls (median 1.1 and 2.0 versus 2.5, P<0.01, P<0.001). Severe coagulopathies may be present in critically ill dogs without concurrent SIRS. APC-resistance is a frequent finding in severely diseased dogs.

  2. Strategies for modulating the inflammatory response after decompression from abdominal compartment syndrome

    PubMed Central

    2012-01-01

    Background Management of the open abdomen is an increasingly common part of surgical practice. The purpose of this review is to examine the scientific background for the use of temporary abdominal closure (TAC) in the open abdomen as a way to modulate the local and systemic inflammatory response, with an emphasis on decompression after abdominal compartment syndrome (ACS). Methods A review of the relevant English language literature was conducted. Priority was placed on articles published within the last 5 years. Results/Conclusion Recent data from our group and others have begun to lay the foundation for the concept of TAC as a method to modulate the local and/or systemic inflammatory response in patients with an open abdomen resulting from ACS. PMID:22472164

  3. Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response.

    PubMed

    Stojanov, Silvia; Hoffmann, Florian; Kéry, Anja; Renner, Ellen D; Hartl, Dominik; Lohse, Peter; Huss, Kristina; Fraunberger, Peter; Malley, James D; Zellerer, Stephanie; Albert, Michael H; Belohradsky, Bernd H

    2006-06-01

    PFAPA syndrome is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and/or cervical adenitis. It is of unknown etiology and manifests usually before 5 years of age. We determined serum and intracellular cytokine levels in six PFAPA patients (4 males, 2 females, mean age 8 years (+/- 1.2 SEM), range 4-13) during the symptom-free period as well as 6-12 hours and 18-24 hours after fever onset. Values were compared to age-matched, healthy controls. Febrile PFAPA attacks led to a significant increase in IL-6 and IFN-gamma serum concentrations compared to symptom-free periods and to controls, with IL-1beta, TNF-alpha and IL-12p70 levels being significantly higher than in controls. Lymphocytic IFN-gamma and CD8+ IL-2 production was consistently significantly elevated compared to healthy children. During the asymptomatic period, serum concentrations of IL-1beta, IL-6, TNF-alpha and IL-12p70 were significantly increased compared to controls. Intracellular TNF-alpha synthesis was not elevated at any time point. Soluble TNFRp55 levels were even lower in between febrile episodes, reaching values comparable to controls during attacks, whereas soluble TNFRp75 levels increased during attacks compared to healthy children. Anti-inflammatory IL-4 in serum was at all times lower in PFAPA patients compared to controls with no difference in levels of intracellular IL-4 and IL-10 or serum IL-10. The observed increase of pro-inflammatory mediators, even between febrile attacks, suggests a dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.

  4. System-wide Mapping of Activated Circuitry in Experimental Systemic Inflammatory Response Syndrome

    PubMed Central

    Gharib, Sina A.; Mar, Daniel; Bomsztyk, Karol; Denisenko, Oleg; Dhanireddy, Shireesha; Liles, W. Conrad; Altemeier, William A.

    2015-01-01

    Sepsis-induced multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in critically ill patients and remains impervious to most therapeutic interventions. We utilized a clinically relevant murine model of systemic inflammatory response syndrome (SIRS) during early MODS induced by ventilator-associated pneumonia to systematically delineate pathways dysregulated in lung, liver, and kidney. We focused on processes commonly activated across at-risk organs and constructed a SIRS-associated network based on connectivity among the gene members of these functionally coherent pathways. Our analyses led to the identification of several putative drivers of early MODS whose expression was regulated by epidermal growth factor receptor. Our unbiased, integrative method is a promising approach to unravel mechanisms in system-wide disorders afflicting multiple compartments such as sepsis-induced MODS, and identify putative therapeutic targets. PMID:26536201

  5. [The HELPP syndrome--evidence of a possible systemic inflammatory response in pre-eclampsia?].

    PubMed

    Balderas-Peña, Luz Ma Adriana; Canales-Muñoz, José Luis; Angulo-Vázquez, José; Anaya-Prado, Roberto; González Ojeda, Alejandro

    2002-07-01

    The principal causes of morbidity and mortality during pregnancy in Mexico, are preeclampsia/eclampsia, obstetric hemorrhage and puerperium complications; this is, 62% of maternal deaths in last years. HELLP syndrome was observed between 5 to 25% of the mortality in pregnancies of 36 weeks or less. To analyze patients with HELLP syndrome in ICU's (Intensive Care Unit) of a Gynecology and Obstetric Hospital, related to the abnormal hematological, hepatic and renal results with the obstetric case history and the clinical complications. A transversal study in patients with HELLP syndrome during 1998 and 1999 were carry out. Peripheral blood with Microangiopathic hemolysis, elevated liver enzymes: AST, ALT over 40 UI/L, even when were LDH lower than 600 UI/L. It was evaluated the hepatic and renal function, platelets count, microangiopathic hemolysis, arterial pressure, seizures, icteric skin color, blindness, visual disturbances, nausea, vomiting and upper quadrant right abdominal pain. In newborn we analyzed gestational age, sex, weight and APGAR. We studied for an association between maternal and biochemical variables with Correlation Pearson Test, and dependence between variables with lineal regression model. 2878 patients with hypertensives disorders in pregnancy (11.64%). The 1.15% (n = 33) had HELLP syndrome with specific maternal mortality of 0.4 per 10,000 live birth, perinatal mortality of 1.62 per 10,000 live birth; and renal damage in 84.5%. Coefficient beta was higher between number of pregnancies to platelets count (-0.33) and creatinine clearance (-0.401). We found an important renal damage, low platelets, elevated liver enzymes in women with two or more pregnancies. Then we propose there are similarities between HELLP syndrome and Systemic Inflammatory Response Syndrome (SIRS) because they could have the same pathophysiology.

  6. Acetyl salicylic acid usage and mortality in critically ill patients with the systemic inflammatory response syndrome and sepsis.

    PubMed

    Eisen, Damon P; Reid, David; McBryde, Emma S

    2012-06-01

    Low doses of acetyl salicylic acid, acting through 15-epi-lipoxin A4, have been shown to be anti-inflammatory in human studies. The manifold effects of acetyl salicylic acid on human physiology potentially may benefit patients with the systemic inflammatory response syndrome after sepsis or tissue trauma. We sought to determine whether acetyl salicylic acid administration at the time of development of systemic inflammatory response syndrome is associated with reduced mortality. Retrospective cohort study of consecutive intensive care unit admissions between April 2000 and November 2009. Australian tertiary referral center. Seven-thousand nine-hundred forty-five intensive care unit admissions examined. The probability of in-hospital death during admissions in which individuals were identified as having systemic inflammatory response syndrome or sepsis was analyzed according to whether they were administered acetyl salicylic acid. Propensity analysis that matched all patients for their probability of being prescribed acetyl salicylic acid was undertaken. Among 5523 patients with a first episode of systemic inflammatory response syndrome, 2082 were administered acetyl salicylic acid in a 24-hr period around the time of systemic inflammatory response syndrome recognition. Propensity analysis showed a 10.9% mortality for acetyl salicylic acid users and 17.2% mortality in the propensity-matched nonusers (absolute risk difference -6.2%; 95% confidence interval -9.5% to -3.5%). Propensity matching also found that acetyl salicylic acid administration was associated with increased risk of renal injury (6.2% vs. 2.9%; absolute risk difference 13.3%; 95% confidence interval 2.5% to 5.0%). In the 970 patients with proven sepsis, acetyl salicylic acid administration was associated with a lower mortality (27.4% vs. 42.2%; absolute risk difference -14.8%; 95% confidence interval -18.9% to -8.6%) after propensity matching. This quasi-experimental study cannot establish a causal

  7. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    PubMed Central

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  8. A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the "post-inflammatory brain syndrome" PIBS.

    PubMed

    Rathbone, Alasdair Timothy Llewelyn; Tharmaradinam, Surejini; Jiang, Shucui; Rathbone, Michel P; Kumbhare, Dinesh A

    2015-05-01

    Post-concussion syndrome is an aggregate of symptoms that commonly present together after head injury. These symptoms, depending on definition, include headaches, dizziness, neuropsychiatric symptoms, and cognitive impairment. However, these symptoms are common, occurring frequently in non-head injured controls, leading some to question the existence of post-concussion syndrome as a unique syndrome. Therefore, some have attempted to explain post-concussion symptoms as post-traumatic stress disorder, as they share many similar symptoms and post-traumatic stress disorder does not require head injury. This explanation falls short as patients with post-concussion syndrome do not necessarily experience many key symptoms of post-traumatic stress disorder. Therefore, other explanations must be sought to explain the prevalence of post-concussion like symptoms in non-head injury patients. Many of the situations in which post-concussion syndrome like symptoms may be experienced such as infection and post-surgery are associated with systemic inflammatory responses, and even neuroinflammation. Post-concussion syndrome itself has a significant neuroinflammatory component. In this review we examine the evidence of neuroinflammation in post-concussion syndrome and the potential role systemic inflammation plays in post-concussion syndrome like symptoms. We conclude that given the overlap between these conditions and the role of inflammation in their etiologies, a new term, post-inflammatory brain syndromes (PIBS), is necessary to describe the common outcomes of many different inflammatory insults. The concept of post-concussion syndrome is in its evolution therefore, the new term post-inflammatory brain syndromes provides a better understanding of etiology of its wide-array of symptoms and the wide array of conditions they can be seen in. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats

    PubMed Central

    Rubio-Ruiz, María Esther; Pérez-Torres, Israel; Diaz-Diaz, Eulises; Pavón, Natalia; Guarner-Lans, Verónica

    2014-01-01

    Aim: Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats. Methods: MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 μmol/L) were measured in the presence or absence of different NSAIDs (10 μmol/L for each). Results: Serum levels of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect. Conclusion: NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders. PMID:25263337

  10. Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion.

    PubMed

    Tadros, Elizabeth M; Frank, Nicholas; Donnell, Robert L

    2013-07-01

    To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy horses and 6 horses with EMS. Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion. Results-Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups. Results supported the hypothesis that EMS affects horses' inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.

  11. Metabolism of Albumin after Continuous Venovenous Hemofiltration in Patients with Systemic Inflammatory Response Syndrome

    PubMed Central

    Chen, Yu; Qin, Xiaodong; Li, Guanwei; Zhou, Bo; Gu, Guosheng; Hong, Zhiwu; Aa, JiYe; Li, Jieshou

    2015-01-01

    Background. The systemic inflammatory response syndrome (SIRS) is characterized by a hypercatabolic state induced by inflammatory mediators. Continuous venovenous hemofiltration (CVVH) stabilizes the internal environment but also aggravates loss of amino acids. The effect of CVVH on protein dynamics is largely unknown. We adopted the stable isotopic tracer technology to investigate how CVVH changed serum albumin metabolism. Methods. Twenty SIRS patients were randomized into low- (2000 mL/h) and high- (4000 mL/h) volume CVVH groups according to the rate of replacement fluid. Eight patients with abdominal infection matched for age, sex, and laboratory index served as controls. Consecutive arterial blood samples were drawn during a primed-constant infusion of two stable isotopes to determine the albumin fractional synthesis rate (FSR) and fractional breakdown rate (FBR). Results. Before treatment, there was no significant difference of FSR and FBR among 3 groups. After CVVH, the albumin FSR in high- and low-volume groups was 7.75 ± 1.08% and 7.30 ± 0.89%, respectively, both higher than in the control (5.83 ± 0.94%). There was no significant difference in albumin FBR after treatment. Conclusions. Protein dynamic indicators could reflect protein synthesis and breakdown state directly and effectively. CVVH increased albumin synthesis, while the breakdown rate remained at a high level independently of the CVVH rate. PMID:25650044

  12. Cinnamaldehyde modulates LPS-induced systemic inflammatory response syndrome through TRPA1-dependent and independent mechanisms.

    PubMed

    Mendes, Saulo J F; Sousa, Fernanda I A B; Pereira, Domingos M S; Ferro, Thiago A F; Pereira, Ione C P; Silva, Bruna L R; Pinheiro, Aruanã J M C R; Mouchrek, Adriana Q S; Monteiro-Neto, Valério; Costa, Soraia K P; Nascimento, José L M; Grisotto, Marcos A G; da Costa, Robson; Fernandes, Elizabeth S

    2016-05-01

    Cinnamaldehyde is a natural essential oil suggested to possess anti-bacterial and anti-inflammatory properties; and to activate transient receptor potential ankyrin 1 (TRPA1) channels expressed on neuronal and non-neuronal cells. Here, we investigated the immunomodulatory effects of cinnamaldehyde in an in vivo model of systemic inflammatory response syndrome (SIRS) induced by lipopolysaccharide. Swiss mice received a single oral treatment with cinnamaldehyde 1 h before LPS injection. To investigate whether cinnamaldehyde effects are dependent on TRPA1 activation, animals were treated subcutaneously with the selective TRPA1 antagonist HC-030031 5 min prior to cinnamaldehyde administration. Vehicle-treated mice were used as controls. Cinnamaldehyde ameliorated SIRS severity in LPS-injected animals. Diminished numbers of circulating mononuclear cells and increased numbers of peritoneal mononuclear and polymorphonuclear cell numbers were also observed. Cinnamaldehyde augmented the number of peritoneal Ly6C(high) and Ly6C(low) monocyte/macrophage cells in LPS-injected mice. Reduced levels of nitric oxide, plasma TNFα and plasma and peritoneal IL-10 were also detected. Additionally, IL-1β levels were increased in the same animals. TRPA1 antagonism by HC-030031 reversed the changes in the number of circulating and peritoneal leukocytes in cinnamaldehyde-treated animals, whilst increasing the levels of peritoneal IL-10 and reducing peritoneal IL-1β. Overall, cinnamaldehyde modulates SIRS through TRPA1-dependent and independent mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Tocilizumab for uncontrollable systemic inflammatory response syndrome complicating adult-onset Still disease

    PubMed Central

    Masui-Ito, Asami; Okamoto, Ryuji; Ikejiri, Kaoru; Fujimoto, Mika; Tanimura, Muneyoshi; Nakamori, Shiro; Murata, Tomohiro; Ishikawa, Eiji; Yamada, Norikazu; Imai, Hiroshi; Ito, Masaaki

    2017-01-01

    Abstract Rationale: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown etiology characterized by evanescent salmon-pink rash, fever spikes, arthralgia, and lymphadenopathy. AOSD usually has a good prognosis, but it can sometimes be fatal, especially when it is complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure. Patient concerns: A previously healthy 26-year-old woman was referred to our hospital for persistent high fever and mild systemic edema. Five days later, the patient presented with dyspnea, hypotension, and anuria. Anasarca developed with massive pleural effusion, ascites, and systemic edema, resulting in an increase of 47 kg in body weight. Diagnoses: The patient was diagnosed as AOSD after infection, malignancy, hematologic disorders, and other autoimmune diseases were excluded. Interventions: We administered tocilizumab, an IL-6 receptor inhibitor, intravenously in addition to cyclosporine, prednisolone, plasma exchange, and continuous hemodiafiltration. Outcomes: The patient's systemic condition improved. After stabilization by all medications, the patient was managed and responded to tocilizumab alone. To the best of our knowledge, this was the first case of severe SIRS complicating AOSD that was successfully treated with an anti- IL-6 receptor antibody. Lessons: SIRS should not be overlooked in a patient with steroid-resistant AOSD and edema. Inhibitors of the IL-6 receptor can be used safely and effectively to control AOSD complicated with severe SIRS. PMID:28723802

  14. Effect of lornoxicam in lung inflammatory response syndrome after operations for cardiac surgery with cardiopulmonary bypass.

    PubMed

    Tsakiridis, Kosmas; Zarogoulidis, Paul; Vretzkakis, Giorgos; Mikroulis, Dimitris; Mpakas, Andreas; Kesisis, Georgios; Arikas, Stamatis; Kolettas, Alexandros; Moschos, Giorgios; Katsikogiannis, Nikolaos; Machairiotis, Nikolaos; Tsiouda, Theodora; Siminelakis, Stavros; Beleveslis, Thomas; Zarogoulidis, Konstantinos

    2014-03-01

    The establishment of Extracorporeal Circulation (EC) significantly contributed to improvement of cardiac surgery, but this is accompanied by harmful side-effects. The most important of them is systemic inflammatory response syndrome. Many efforts have been undertaken to minimize this problem but unfortunately without satisfied solution to date. Lornoxicam is a non steroid anti-inflammatory drug which temporally inhibits the cycloxygenase. In this clinical trial we study the effect of lornoxicam in lung inflammatory response after operations for cardiac surgery with cardiopulmonary bypass. In our study we conclude 14 volunteers patients with ischemic coronary disease undergoing coronary artery bypass grafting with EC. In seven of them 16 mg lornoxicam was administered iv before the anesthesia induction and before the connection in heart-lung machine. In control group (7 patients) we administered the same amount of normal saline. Both groups are equal regarding pro-operative and intra-operative parameters. The inflammatory markers were calculated by Elisa method. We measured the levels of cytokines (IL-6, IL-8, TNF-a), adhesion molecules (ICAM-1, e-Selectin, p-Selectin) and matrix metaloproteinase-3 (MMP-3) just after anesthesia induction, before and after cardiopulmonary bypass, just after the patients administration in ICU and after 8 and 24 hrs. In all patients we estimated the lung's inflammatory reaction with lung biopsy taken at the begging and at the end of the operation. We calculated hemodynamics parameters: Cardiac Index (CI), Systemic Vascular Resistance Index (SVRI), Pulmonary Vascular Resistance Index (PVRI), Left Ventricular Stroke Work Index (LVSWI), Right Ventricular Stroke Work Index (RVSWI), and the Pulmonary arterial pressure, and respiratory parameters too: alveolo-arterial oxygen difference D (A-a), intrapulmonary shunt (Qs/Qt) and pulmonary Compliance. IL-6 levels of lornoxicam group were statistical significant lower at 1st postoperative day

  15. A burning issue: do sepsis and systemic inflammatory response syndrome (SIRS) directly contribute to cardiac dysfunction?

    PubMed

    Ren, Jun; Wu, Shan

    2006-01-01

    Heart disease is among the leading causes of death in all populations. Cardiac dysfunctions are major complications in patients with advanced viral or bacterial infection, severe trauma and burns accompanied with multiple organ failure - collectively known as systemic inflammatory response syndrome (SIRS). SIRS, which is often subsequent to sepsis, is clinically featured by hypotension, tachypnea, hypo- or hyperthermia, leukocytosis and myocardial dysfunction. The striking association between inflammation and cardiac dysfunction not only prognoses likelihood of survival in patients with SIRS but also prompts the necessity of understanding the pathophysiology of cardiac dysfunction in SIRS, so that effective therapeutic regimen may be identified. Compelling evidence has shown significant and independent link among inflammation, sepsis, insulin resistance and cardiac dysfunction. Several cytokine signaling molecules have been speculated to play important roles in the onset of cardiac dysfunction under SIRS including endothelin-1 and toll-like receptor. Involvement of these pathways in cardiac dysfunction has been convincingly validated with transgenic studies. Nevertheless, the precise mechanism of action underscoring inflammation-induced cardiac contractile dysfunction is far from being clear. Given the substantial impact of inflammation and SIRS on health care, ecosystems and national economy, it is imperative to understand the cellular mechanisms responsible for cardiac contractile dysfunction under inflammation and sepsis so that new and effective therapeutic strategy against such devastating heart problems may be developed.

  16. The relationship between intraoperative blood transfusion and postoperative systemic inflammatory response syndrome.

    PubMed

    Ferraris, Victor A; Ballert, Erik Q; Mahan, Angela

    2013-04-01

    Previous observations suggest that intraoperative blood transfusion (IBT) is a risk factor for adverse postoperative outcomes. IBT alters immune function and may predispose to systemic inflammatory response syndrome (SIRS). Patients in the American College of Surgeons National Surgical Quality Improvement Project database were studied over a 5-year period. Logistic regression identified predictors of SIRS. Propensity matching was used to obtain a balanced set of patients with equivalent preoperative risks for IBT. Of 553,288 inpatients, 19,968 (3.6%) developed postoperative SIRS, and 40,378 (7.2%) received IBT. Mortality in patients with SIRS was 13-fold higher than in those without SIRS (13.5% vs 1.0%, P < .001). Multivariate analysis identified the amount of blood transfused during IBT as a significant predictor for development of SIRS (odds ratio, 2.2; P < .0001). After propensity matching, 33,507 matched patients with IBT had significantly increased risk for SIRS compared with non-SIRS matched patients (12.0% vs 6.5%, P < .001). There is a significant association between IBT and the development of SIRS. IBT may induce SIRS, and reductions in IBT may decrease the incidence of postoperative SIRS. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Evaluation of serum thyroid hormones in dogs with systemic inflammatory response syndrome or sepsis.

    PubMed

    Pashmakova, Medora B; Bishop, Micah A; Steiner, Jörg M; Suchodolski, Jan S; Barr, James W

    2014-01-01

    To determine whether dogs with systemic inflammatory response syndrome (SIRS) or sepsis have derangements in serum thyroid hormone concentrations and to evaluate whether such derangements relate to illness severity or outcome. Prospective observational study. Dogs hospitalized with SIRS or sepsis between May and December 2010 were included. Serum thyroid hormone concentrations were measured in all dogs. Data obtained on admission were used to calculate the Acute Patient Physiologic and Laboratory Evaluation (APPLE) scores. University teaching hospital. Twenty-two consecutive client-owned dogs hospitalized with SIRS or sepsis were enrolled; 18 dogs completed the study and 4 dogs were excluded for incomplete data. Forty-nine healthy dogs owned by volunteers were used as controls. None. Decreased total thyroxine (TT4) concentrations were documented in all septic and 7/9 dogs with SIRS. Free T4 concentrations were decreased, but were within the reference interval in 12/18 dogs with SIRS or sepsis compared to control dogs (P < 0.001). Dogs with increased APPLE(fast) scores were less likely to survive (P = 0.017). Dogs with SIRS or sepsis have derangements in measured serum thyroid hormones. No relationships were identified between thyroid hormone concentrations and survival. The APPLE(fast) score was the only variable predictive of poor outcome. © Veterinary Emergency and Critical Care Society 2014.

  18. Inflammatory Cardiomyopathic Syndromes.

    PubMed

    Trachtenberg, Barry H; Hare, Joshua M

    2017-09-15

    Inflammatory activation occurs in nearly all forms of myocardial injury. In contrast, inflammatory cardiomyopathies refer to a diverse group of disorders in which inflammation of the heart (or myocarditis) is the proximate cause of myocardial dysfunction, causing injury that can range from a fully recoverable syndrome to one that leads to chronic remodeling and dilated cardiomyopathy. The most common cause of inflammatory cardiomyopathies in developed countries is lymphocytic myocarditis most commonly caused by a viral pathogenesis. In Latin America, cardiomyopathy caused by Chagas disease is endemic. The true incidence of myocarditis is unknown to the limited utilization and the poor sensitivity of endomyocardial biopsies (especially for patchy diseases such as lymphocytic myocarditis and sarcoidosis) using the gold-standard Dallas criteria. Emerging immunohistochemistry criteria and molecular diagnostic techniques are being developed that will improve diagnostic yield, provide additional clues into the pathophysiology, and offer an application of precision medicine to these important syndromes. Immunosuppression is recommended for patients with cardiac sarcoidosis, giant cell myocarditis, and myocarditis associated with connective tissue disorders and may be beneficial in chronic viral myocarditis once virus is cleared. Further trials of immunosuppression, antiviral, and immunomodulating therapies are needed. Together, with new molecular-based diagnostics and therapies tailored to specific pathogeneses, the outcome of patients with these disorders may improve. © 2017 American Heart Association, Inc.

  19. Metabolic and inflammatory responses to the common sweetener stevioside and a glycemic challenge in horses with equine metabolic syndrome.

    PubMed

    Elzinga, S E; Rohleder, B; Schanbacher, B; McQuerry, K; Barker, V D; Adams, A A

    2017-07-01

    Extracts derived from the leaves of the stevia plant (stevioside) are commonly used as sweeteners for humans and horses. Stevioside appears to be safe for human consumption, including for individuals with insulin dysregulation. In the horse, the safety or metabolic effects of stevioside on normal animals or on those with metabolic dysfunction are unknown. Furthermore, the inflammatory response to a glycemic challenge or to stevioside in horses is not well defined. Therefore, the objective of this study was to measure the effects of stevioside and a glycemic challenge on insulin, glucose, and inflammatory responses in horses with a common metabolic dysfunction (equine metabolic syndrome or EMS) compared with non-EMS controls. To accomplish this, 15 horses were selected; 8 EMS and 7 age-matched controls. An oral sugar test was performed using Karo corn syrup (karo) or stevioside in a random crossover design. Horses were given 0.15 mL/kg body weight of karo or its equivalent grams of sugar in stevia dissolved in water. Blood samples were collected by jugular venipuncture before administration of either stevia or karo and at 60 and 240 min after administration. Serum was used for glucose and insulin determination and plasma for isolation of peripheral blood mononuclear cells (PBMCs) for inflammatory cytokine analysis via flow cytometry and reverse transcription PCR (RT-PCR). Stevia appeared to stimulate lower glycemic and insulinemic responses when compared to karo, in particular in EMS horses. EMS and control horses had inverse inflammatory responses to administration of either stevia or karo with EMS horses having a proinflammatory response (P ≤ 0.05). These data provide evidence as to why horses with EMS may be predisposed to developing laminitis, potentially as a result of an exaggerated inflammatory response to glycemic and insulinemic responses. Furthermore, the data provide new avenues for exploring mechanisms behind the syndrome, in particular when using a

  20. Circulating Plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS).

    PubMed

    Caserta, Stefano; Kern, Florian; Cohen, Jonathan; Drage, Stephen; Newbury, Sarah F; Llewelyn, Martin J

    2016-06-20

    Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these 'circulating inflammation-related microRNAs' (CIR-miRNAs) were 2.64 (IQR: 2.10-3.29) and 1.52 (IQR: 1.15-1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742-0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets.

  1. Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes.

    PubMed

    Kumaraswamy, Sunil B; Linder, Adam; Åkesson, Per; Dahlbäck, Björn

    2012-12-12

    Apolipoprotein M (apoM) is present in 5% of high-density lipoprotein (HDL) particles in plasma. It is a carrier of sphingosine-1-phosphate (S1P), which is important for vascular barrier protection. The aim was to determine the plasma concentrations of apoM during sepsis and systemic inflammatory response syndrome (SIRS) and correlate them to levels of apolipoprotein A-I (apoA1), apolipoprotein B (apoB), HDL-, and low-density lipoprotein (LDL)-cholesterol. Plasma samples from patients with (1), severe sepsis with shock (n = 26); (2), severe sepsis without shock (n = 44); (3), sepsis (n = 100); (4), infections without SIRS (n = 43); and (5) SIRS without infection (n = 20) were analyzed. The concentrations of apoM, apoA1, and apoB were measured with enzyme-linked immunosorbent assays (ELISAs). Total, HDL-, and LDL-cholesterol concentrations were measured with a commercial HDL/LDL cholesterol test. ApoM concentrations correlated negatively to acute-phase markers. Thus, apoM behaved as a negative acute-phase protein. Decreased values were observed in all patient groups (P < 0.0001), with the most drastic decreases observed in the severely sick patients. ApoM levels correlated strongly to those of apoA1, apoB, HDL, and LDL cholesterol. The HDL and LDL cholesterol levels were low in all patient groups, as compared with controls (P < 0.0001), in particular, HDL cholesterol. ApoA1 and apoB concentrations were low only in the more severely affected patients. During sepsis and SIRS, the plasma concentrations of apoM decrease dramatically, the degree of decrease reflecting the severity of the disease. As a carrier for barrier-protective S1P in HDL, the decrease in apoM could contribute to the increased vascular leakage observed in sepsis and SIRS.

  2. Sepsis biomarkers in neutropaenic systemic inflammatory response syndrome patients on standard care wards.

    PubMed

    Ratzinger, Franz; Haslacher, Helmuth; Perkmann, Thomas; Schmetterer, Klaus G; Poeppl, Wolfgang; Mitteregger, Dieter; Dorffner, Georg; Burgmann, Heinz

    2015-08-01

    Neutropaenic patients are at a high risk of contracting severe infections. In particular, in these patients, parameters with a high negative predictive value are desirable for excluding infection or bacteraemia. This study evaluated sepsis biomarkers in neutropaenic patients suffering from systemic inflammatory response syndrome (SIRS). Further, the predictive capacities of evaluated biomarkers in neutropaenic SIRS patients were compared to non-neutropaenic SIRS patients. In this prospective observational cohort study, patients with clinically suspected sepsis were screened. The predictive capacities of procalcitonin (PCT), C-reactive protein and lipopolysaccharide-binding protein (LBP) in neutropaenic SIRS patients were evaluated in terms of their potential to identify infection or bacteraemia and were compared to results for non-neutropaenic SIRS patients. To select an appropriate control cohort, propensity score matching was applied, balancing confounding factors between neutropaenic and non-neutropaenic SIRS patients. Of 3370 prospectively screened patients with suspected infection, 51 patients suffered from neutropaenic SIRS. For the identification of infection, none of the assessed biomarkers presented a clinically relevant discriminatory potency. Lipopolysaccharide-binding protein and PCT demonstrated discriminatory capacity to discriminate between nonbacteraemic and bacteraemic SIRS in patients with neutropaenia [receiver-operating characteristics-area under the curves (ROC-AUCs): 0.860, 0.818]. In neutropaenic SIRS patients, LBP had a significantly better ROC-AUC than in a comparable non-neutropaenic patient cohort for identifying bacteraemia (P = 0.01). In neutropaenic SIRS patients, none of the evaluated biomarkers was able to adequately identify infection. LBP and PCT presented a good performance in identifying bacteraemia. Therefore, these markers could be used for screening purposes to increase the pretest probability of blood culture analysis.

  3. [Non-glucose carbohydrates in the parenteral nutrition of patients with systemic inflammatory response syndrome].

    PubMed

    López Martínez, J; Sánchez Castilla, M; de Juana Velasco, P; Díaz Abad, R; Rodríguez Roldán, J M; García de Lorenzo y Mateos, A; Del Nogal Sáez, F

    1999-01-01

    To compare tolerance of two sources of isocaloric intake (fructose-glucose-xylitol mixture [FGX] versus glucose) in parenteral nutrition for patients with systemic inflammatory response syndrome (SIRS). Open, prospective, cohort and randomized study. Intensive Care Unit. Two groups of patients admitted in ICU: acute pneumonia with sepsis, and necro-hemorrhagic pancreatitis. Criteria of exclusion were: diabetes, previous hypertriglyceridemia, renal failure with serum creatinine > 3 mg/dL on admission in ICU, or hyperbilirrubinemia > 2.5 mg/dL. Parenteral nutrition (TPN), consisting of 1.4 g AA + Lipids 1.3 g + carbohydrates 4 g/kg/d, (either glucose or FGX at random) was administered. Basal levels and days 1st, 4th and 10th plasma glucose, triglycerides, cholesterol, uric acid were determined, and blood venous gases as well. Capillary glycemia was measured every 6 hours and insulin given if glucose levels rose above 180 mg/dL. Fisher's exact test; Student t-test; Mann-Whitney test. Data as mean and SD. During 48 months, 119 patients admitted in the ICU (72 with pneumonia and 47 with pancreatitis) were included. In pneumonia, tolerance was similar with both intakes; glycemia was kept at the same level in both, but the amount of insulin given was significantly more in those patients fed on glucose (p < 0.05). Nevertheless, resting blood glucose and triglyceride levels were higher in pancreatitic patients, and more insulin was required. Those on FGX had lower triglyceride plasma levels (p < 0.05) and less insulin was given throughout the study. Glycemia was kept lower though no statistical significance was reached (p < 0.1). No hyperuricemia nor lactic acidosis was found.

  4. Characteristics of leptospirosis with systemic inflammatory response syndrome: a multicenter study.

    PubMed

    Yilmaz, Hava; Turhan, Vedat; Yasar, Kadriye Kart; Hatipoglu, Mustafa; Sunbul, Mustafa; Leblebicioglu, Hakan

    2015-12-21

    Leptospirosis is a common zoonotic infection in the world. In patients with leptospirosis, in case of presence of Systemic Inflammatory Response Syndrome (SIRS), clinical and laboratory findings can be mistaken for sepsis due to other causes of infection. The purpose of this study is to assess the clinical and laboratory parameters of patients with leptospirosis in terms of the presence of SIRS and to examine the association of these with mortality. One hundred fifty-seven patients were included in the study. The patients were classified according to the presence or absence of SIRS and divided into SIRS (+) and SIRS (-). Patient files were retrospectively evaluated. Clinical features and laboratory data were compared, and risk factors associated with mortality were determined. SIRS (+) was found in 70 % (n = 110) of patients who had signs on admission. Comparison of the clinical symptoms and findings of organ systems in the SIRS (+) and SIRS (-) showed that abdominal pain and vomiting were significantly more common in the SIRS (+) than in the SIRS (-) (p = 0.025 and p = 0.046, respectively). BUN and serum creatinine levels were significantly higher in the SIRS (+) than in the SIRS (-) (p = 0.002 and p < 0.001, respectively). In follow-up posterior-anterior chest radiography, pathological findings improved in 58.8 % (n = 40) of patients in the SIRS (+) and 27.3 % (n = 9) of patients in the SIRS (-) (p = 0.003). The mortality rate of the SIRS (+) and SIRS (-) was not significantly different (p = 0.868). In patients with positive SIRS findings, while examining the etiology of sepsis, leptospirosis should come to mind especially in endemic areas for differential diagnosis. Early initiation of antibiotic and supportive therapy can be lifesaving in these patients.

  5. Epidemiology of systemic inflammatory response syndrome and sepsis in cats hospitalized in a veterinary teaching hospital.

    PubMed

    Babyak, Jonathan M; Sharp, Claire R

    2016-07-01

    OBJECTIVE To describe the epidemiology of the systemic inflammatory response syndrome (SIRS) and sepsis in cats hospitalized in a veterinary teaching hospital. DESIGN Observational study. ANIMALS 246 client-owned cats. PROCEDURES During a 3-month period, daily treatment records were evaluated for all hospitalized cats. Information extracted included signalment, temperature, heart rate, respiratory rate, diagnostic test results, diagnosis, duration of hospitalization, and outcome (survival or death). Cats were classified into 1 of 4 disease categories (sepsis [confirmed infection and SIRS], infection [confirmed infection without SIRS], noninfectious SIRS [SIRS without a confirmed infection], and no SIRS [no SIRS or infection]). RESULTS Of the 246 cats, 26 and 3 were hospitalized 2 and 3 times, respectively; thus, 275 hospitalizations were evaluated. When SIRS was defined as the presence of ≥ 2 of 4 SIRS criteria, 17 cats had sepsis, 16 had infections, 81 had noninfectious SIRS, and 161 were classified in the no SIRS category at hospital admission. The prevalence of sepsis at hospital admission was 6.2 cases/100 admissions. Four cats developed sepsis while hospitalized, resulting in a sepsis incidence rate of 1.5 cases/100 hospital admissions. Four of 17 cats with sepsis at hospital admission and 3 of 4 cats that developed sepsis while hospitalized died or were euthanized, resulting in a mortality rate of 33.3% for septic cats; 239 hospitalizations resulted in survival, 28 resulted in euthanasia, and 8 resulted in death. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that many hospitalized cats have evidence of SIRS and some have sepsis. In cats, sepsis is an important clinical entity with a high mortality rate.

  6. Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients

    PubMed Central

    Zadravecz, Frank J.; Winslow, Christopher; Howell, Michael D.; Edelson, Dana P.

    2015-01-01

    Rationale: Tools that screen inpatients for sepsis use the systemic inflammatory response syndrome (SIRS) criteria and organ dysfunctions, but most studies of these criteria were performed in intensive care unit or emergency room populations. Objectives: To determine the incidence and prognostic value of SIRS and organ dysfunctions in a multicenter dataset of hospitalized ward patients. Methods: Hospitalized ward patients at five hospitals from November 2008 to January 2013 were included. SIRS and organ system dysfunctions were defined using 2001 International Consensus criteria. Patient characteristics and in-hospital mortality were compared among patients meeting two or more SIRS criteria and by the presence or absence of organ system dysfunction. Measurements and Main Results: A total of 269,951 patients were included in the study, after excluding 48 patients with missing discharge status. Forty-seven percent (n = 125,841) of the included patients met two or more SIRS criteria at least once during their ward stay. On ward admission, 39,105 (14.5%) patients met two or more SIRS criteria, and patients presenting with SIRS had higher in-hospital mortality than those without SIRS (4.3% vs. 1.2%; P < 0.001). Fourteen percent of patients (n = 36,767) had at least one organ dysfunction at ward admission, and those presenting with organ dysfunction had increased mortality compared with those without organ dysfunction (5.3% vs. 1.1%; P < 0.001). Conclusions: Almost half of patients hospitalized on the wards developed SIRS at least once during their ward stay. Our findings suggest that screening ward patients using SIRS criteria for identifying those with sepsis would be impractical. PMID:26158402

  7. Severe sepsis and systemic inflammatory response syndrome in emergency department patients with suspected severe infection.

    PubMed

    Gille-Johnson, Patrik; Hansson, Karin E; Gårdlund, Bengt

    2013-03-01

    Severe sepsis is a common condition with a reported high mortality, but most studies have been confined to intensive care unit (ICU) populations. The systemic inflammatory response syndrome (SIRS) has been used to define sepsis, however its usefulness has been questioned. Our aim was to describe the prevalence and clinical impact of severe sepsis and SIRS in patients admitted from the emergency department (ED) with a suspected serious infection. Four hundred and four adult patients were enrolled prospectively from the ED. Variables defining severe sepsis and SIRS were measured and the relationship between severe sepsis, SIRS, and the clinical course was analyzed. Infections were diagnosed in 344 patients (85%). The overall mortality rate at 28 days was 2.7%, and 4.5% of patients were treated in the ICU. Patients with severe sepsis within 24 h of admission (42%) were more likely to suffer a critical course (ICU admission 9.0%, death 5.1%; p < 0.001). While SIRS was observed in 72% of the subjects at presentation, it was not associated with severe sepsis within 24 h or a subsequent critical course. Furthermore, 23% of patients with severe sepsis within 24 h did not present with SIRS. Severe sepsis was a common condition among ED patients with a clinically suspected serious infection. Mortality was low compared with results from the ICU setting, suggesting that severe sepsis is a more benign disease than earlier reported. As a tool for the definition of sepsis and for the selection of patients for clinical sepsis trials, SIRS lacks acceptable discriminative ability in an ED population with a high prevalence of serious infections.

  8. A role for leptin in the systemic inflammatory response syndrome (SIRS) and in immune response.

    PubMed

    Waelput, W; Brouckaert, P; Broekaert, D; Tavernier, J

    2002-09-01

    Leptin was originally identified as an adipocyte-derived cytokine with a key role in the regulation of the energy balance. Subsequent research has, however, revealed that leptin's biological action is not restricted to its effects on appetite and food intake, but rather has a much more pleiotropic character. Evidence is now accumulating that it has important functions in reproduction, hematopoiesis, HPA-axis endocrinology and angiogenesis. In this review, we have focused on the effects of leptin in the immune system, which can be found in both the antigen-specific immunity and in the inflammatory effector system.

  9. [Neopterin levels and systemic inflammatory response syndrome in pediatric critically ill patients].

    PubMed

    Gil-Gómez, Raquel; Blasco-Alonso, Javier; Sánchez-Yáñez, Pilar; Rosa-Camacho, Vanessa; Milano Manso, Guillermo

    2017-04-22

    Neopterin and biopterin are sub-products of redox reactions, which act as cofactors of enzymes responsible for nitric oxide production. The hypothesis is presented that plasma neopterin and biopterin evolve differently during the first days in a critically ill child. A single-centre prospective observational study was conducted on patients 7 days to 14 years admitted to our Paediatric Intensive Care Unit (PICU) and that met Systemic inflammatory response syndrome (SIRS) criteria. Neopterin and biopterin levels, as well as other acute phase reactants, were collected at admission and at 24 h. A total of 28 patients were included, of which 78.9% were male, The median age was 5.04 years (interquartile range [IQR] 1.47-10.26), and PRISM II 2.0% (IQR 1.1-5.0). Mechanical ventilation (MV) was used in 90% of patients, with a median duration of 6.0 hrs (IQR 3.7-102.0). The median length of stay in PICU was 5.0 days (IQR 2.7-18.7), maximum VIS mean of 0 (IQR 0-14). Baseline neopterin level was 2.3±1.2 nmol/l and at 24 h it was 2.3±1.4 nmol/l. Baseline biopterin was 1.3±0.5 nmol/l and 1.4±0.4 nmol/l at 24 h. Neopterin levels were significantly higher in patients with PICU length of stay > 6 days (P=.02), patients who needed MV >24 h (P=.023), and those who developed complications (P=.05). Neopterin correlates directly and is statistically significant with the duration of MV (rho=.6, P=.011), PICU length of stay (rho=.75, P<.0001), and VIS (rho=.73, P=.001). Additionally, biopterin directly correlates with the PRISM (rho=.61, P=.008). There is a higher neopterin level when there is a longer PICU stay, higher VIS score, longer time on MV, and occurrence of complications, indicating the involvement of an activation of the cellular immune system. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  10. Metabolic Syndrome and Inflammatory Responses to Long-Term Particulate Air Pollutants

    PubMed Central

    Chen, Jiu-Chiuan; Schwartz, Joel

    2008-01-01

    Background Human data linking inflammation with long-term particulate matter (PM) exposure are still lacking. Emerging evidence suggests that people with metabolic syndrome (MS) may be a more susceptible population. Objectives Our goal was to examine potential inflammatory responses associated with long-term PM exposure and MS-dependent susceptibility. Methods We conducted secondary analyses of white blood cell (WBC) count and MS data from The Third National Health and Nutrition Examination Survey and PM10 (PM with aerodynamic diameter < 10 μm) data from the U.S. Environmental Protection Agency Aerometric Information Retrieval System. Estimated 1-year PM10 exposures were aggregated at the centroid of each residential census-block group, using distance-weighted averages from all monitors in the residing and adjoining counties. We restricted our analyses to adults (20–89 years of age) with normal WBC (4,000–11,000 × 106/L), no existing cardiovascular disease, complete PM10 and MS data, and living in current residences > 1 year (n = 2,978; age 48.5 ± 17.8 years). Mixed-effects models were constructed to account for autocorrelation and potential confounders. Results After adjustment for demographics, socioeconomic factors, lifestyles, residential characteristics, and MS, we observed a statistically significant association between WBC count and estimated local PM10 levels (p = 0.035). Participants from the least polluted areas (1-year PM10 < 1st quartile cutoff: 27.8 μg/m3) had lower WBC counts than the others (difference = 145 × 106/L; 95% confidence interval, 10–281). We also noted a graded association between PM10 and WBC across subpopulations with increasing MS components, with 91 × 106/L difference in WBC for those with no MS versus 214, 338, and 461 × 106/L for those with 3, 4, and 5 metabolic abnormalities (trend-test p = 0.15). Conclusions Our study revealed a positive association between long-term PM exposure and hematological markers of

  11. Effect of sepsis and systemic inflammatory response syndrome on neonatal hearing screening outcomes following gentamicin exposure.

    PubMed

    Cross, Campbell P; Liao, Selena; Urdang, Zachary D; Srikanth, Priya; Garinis, Angela C; Steyger, Peter S

    2015-11-01

    Hearing loss in neonatal intensive care unit (NICU) graduates range from 2% to 15% compared to 0.3% in full-term births, and the etiology of this discrepancy remains unknown. The majority of NICU admissions receive potentially ototoxic aminoglycoside therapy, such as gentamicin, for presumed sepsis. Endotoxemia and inflammation are associated with increased cochlear uptake of aminoglycosides and potentiated ototoxicity in mice. We tested the hypothesis that sepsis or systemic inflammatory response syndrome (SIRS) and intravenous gentamicin exposure increases the risk of hearing loss in NICU admissions. The Institutional Review Board at Oregon Health & Science University (OHSU) approved this study design. Two hundred and eight infants met initial criteria, and written, informed consent were obtained from parents or guardians of 103 subjects ultimately enrolled in this study. Prospective data from 91 of the enrolled subjects at OHSU Doernbecher Children's Hospital Neonatal Care Center were processed. Distortion product otoacoustic emissions (DPOAEs; f2 frequency range: 2063-10,031 Hz) were obtained prior to discharge to assess auditory performance. To pass the DPOAE screen, normal responses in >6 of 10 frequencies in both ears were required; otherwise the subject was considered a "referral" for a diagnostic hearing evaluation after discharge. Cumulative dosing data and diagnosis of neonatal sepsis or SIRS were obtained from OHSU's electronic health record system, and the data processed to obtain risk ratios. Using these DPOAE screening criteria, 36 (39.5%) subjects would be referred. Seventy-four (81%) subjects had intravenous gentamicin exposure. Twenty (22%) had ≥4 days of gentamicin, and 71 (78%) had <4 days. The risk ratio (RR) of referral with ≥4 days of gentamicin was 1.92 (p=0.01). Eighteen subjects had sepsis or met neonatal SIRS criteria, 9 of whom had ≥5 days of gentamicin and a DPOAE referral risk ratio of 2.12 (p=0.02) compared to all other subjects

  12. In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients.

    PubMed

    Sasse, Michael; Dziuba, Friederike; Jack, Thomas; Köditz, Harald; Kaussen, Torsten; Bertram, Harald; Beerbaum, Philipp; Boehne, Martin

    2015-08-01

    Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused particles may exacerbate inflammatory syndromes since they activate the coagulation cascade and alter inflammatory response or microvascular perfusion. In a randomized, controlled, prospective trial, we have previously shown that particle-retentive in-line filtration prevented major complications in critically ill children. Now, we investigated the effect of in-line filtration on major complications in the subgroup of cardiac patients. Children admitted to tertiary pediatric intensive care unit were randomized to either control or filter group obtaining in-line filtration throughout complete infusion therapy. Risk differences and 95 % confidence intervals (CI) of several complications such as SIRS, sepsis, mortality, various organ failure and dysfunction were compared between both groups using the Wald method. 305 children (n = 150 control, n = 155 filter group) with cardiac diseases were finally analyzed. The majority was admitted after cardiac surgery with CPB. Risk of SIRS (-11.3 %; 95 % CI -21.8 to -0.5 %), renal (-10.0 %; 95 % CI -17.0 to -3.0 %) and hematologic (-8.1 %; 95 % CI -14.2 to -0.2 %) dysfunction were significantly decreased within the filter group. No risk differences were demonstrated for occurrence of sepsis, any other organ failure or dysfunctions between both groups. Infused particles might aggravate a systemic hypercoagulability and inflammation with subsequent organ malfunction in pediatric cardiac intensive care patients. Particle-retentive in-line filtration might be effective in preventing SIRS and maintaining renal and hematologic function. In-line filtration offers a novel therapeutic option to decrease morbidity in cardiac intensive care.

  13. Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome

    PubMed Central

    Torene, Rebecca; Nirmala, Nanguneri; Obici, Laura; Cattalini, Marco; Tormey, Vincent; Caorsi, Roberta; Starck-Schwertz, Sandrine; Letzkus, Martin; Hartmann, Nicole; Abrams, Ken; Lachmann, Helen; Gattorno, Marco

    2017-01-01

    Objective To explore whether gene expression profiling can identify a molecular mechanism for the clinical benefit of canakinumab treatment in patents with tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Blood samples were collected from 20 patients with active TRAPS who received canakinumab 150 mg every 4 weeks for 4 months in an open-label proof-of-concept phase II study, and from 20 aged-matched healthy volunteers. Gene expression levels were evaluated in whole blood samples by microarray analysis for arrays passing quality control checks. Results Patients with TRAPS exhibited a gene expression signature in blood that differed from that in healthy volunteers. Upon treatment with canakinumab, many genes relevant to disease pathogenesis moved towards levels seen in the healthy volunteers. Canakinumab downregulated the TRAPS-causing gene (TNF super family receptor 1A (TNFRSF1A)), the drug-target gene (interleukin (IL)-1B) and other inflammation-related genes (eg, MAPK14). In addition, several inflammation-related pathways were evident among the differentially expressed genes. Canakinumab treatment reduced neutrophil counts, but the observed expression differences remained after correction for this. Conclusions These gene expression data support a model in which canakinumab produces clinical benefit in TRAPS by increasing neutrophil apoptosis and reducing pro-inflammatory signals resulting from the inhibition of IL-1β. Notably, treatment normalised the overexpression of TNFRSF1A, suggesting that canakinumab has a direct impact on the main pathogenic mechanism in TRAPS. Trial registration number NCT01242813. PMID:27474763

  14. Similar Metabolic, Innate Immunity, and Adipokine Profiles in Adult and Pediatric Sepsis Versus Systemic Inflammatory Response Syndrome-A Pilot Study.

    PubMed

    Tavladaki, Theonymfi; Spanaki, Anna Maria; Dimitriou, Helen; Kondili, Efmorfia; Choulaki, Christianna; Georgopoulos, Dimitris; Briassoulis, George

    2017-08-12

    To examine whether the septic profiles of heat shock protein 72, heat shock protein 90α, resistin, adiponectin, oxygen consumption, CO2 production, energy expenditure, and metabolic pattern, along with illness severity, nutritional, and inflammatory indices, differ between adult and pediatric patients compared with systemic inflammatory response syndrome and healthy controls. To evaluate whether these biomolecules may discriminate sepsis from systemic inflammatory response syndrome in adult and pediatric patients. Prospective cohort study. University ICU and PICU. Seventy-eight adults (sepsis/23; systemic inflammatory response syndrome/23; healthy controls/33), 67 children (sepsis/18; systemic inflammatory response syndrome/23; controls/27), mechanically ventilated. None. Flow cytometry determined mean fluorescence intensity for monocyte or neutrophil heat shock protein expression. Resistin, adiponectin, and extracellular heat shock proteins were measured using enzyme-linked immunosorbent assay; energy expenditure by E-COVX (GE Healthcare). Genomic DNA was extracted with PureLink Genomic DNA kit (Invitrogen, Carlsbad, CA) to detect heat shock protein 72 single nucleotide polymorphisms. Similarly, in adult and pediatric patients, Acute Physiology and Chronic Evaluation-II/Acute Physiology and Pediatric Risk of Mortality-III, Simplified Acute Physiology Score-III, C-reactive protein, lactate, and resistin were higher and myocardial contractility, monocyte heat shock protein 72, oxygen consumption, CO2 production, energy expenditure, metabolic pattern, glucose, and albumin lower in sepsis compared with systemic inflammatory response syndrome or controls (p < 0.05). For discriminating sepsis from systemic inflammatory response syndrome, resistin, extracellular heat shock protein 90α, and lactate achieved a receiver operating characteristic curve greater than 0.80 in children and greater than 0.75 in adults (p < 0.05). In both, adults and children, genotype heat shock

  15. Palmitoyl acyltransferase DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome

    PubMed Central

    Beard, Richard S.; Yang, Xiaoyuan; Meegan, Jamie E.; Overstreet, Jonathan W.; Yang, Clement G.Y.; Elliott, John A.; Reynolds, Jason J.; Cha, Byeong J.; Pivetti, Christopher D.; Mitchell, David A.; Wu, Mack H.; Deschenes, Robert J.; Yuan, Sarah Y.

    2016-01-01

    Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency (Zdhhc21dep/dep) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21dep/dep display blunted barrier dysfunction and leucocyte adhesion, whereas leucocytes from these mice did not show altered adhesiveness. Furthermore, inflammation enhances PLCβ1 palmitoylation and signalling activity, effects significantly reduced in Zdhhc21dep/dep and rescued by DHHC21 overexpression. Likewise, overexpression of wild-type, not mutant, PLCβ1 augments barrier dysfunction. Altogether, these data suggest the involvement of DHHC21-mediated PLCβ1 palmitoylation in endothelial inflammation. PMID:27653213

  16. Mitochondria-Targeted Antioxidants and Uncouplers of Oxidative Phosphorylation in Treatment of the Systemic Inflammatory Response Syndrome (SIRS).

    PubMed

    Zakharova, Vlada V; Pletjushkina, Olga Yu; Zinovkin, Roman A; Popova, Ekaterina N; Chernyak, Boris V

    2017-05-01

    Systemic inflammatory response syndrome (SIRS) development is accompanied by mitochondrial dysfunction and excessive ROS production. Mitochondrial dysfunctions also occur in many SIRS-related diseases and may be critical for their pathogenesis; therefore, a use of mitochondria-targeted drugs is a promising trend in SIRS research and therapy. Here, we review recent studies concerning the application of the mitochondria-targeted antioxidants and uncouplers of oxidative phosphorylation in animal models of SIRS and related diseases. We propose that a new class of uncouplers of oxidative phosphorylation, lipophilic cations could be a base for a new generation of drugs for SIRS treatment. J. Cell. Physiol. 232: 904-912, 2017. © 2016 Wiley Periodicals, Inc.

  17. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults.

    PubMed

    Raschke, Robert A; Garcia-Orr, Roxanne

    2011-10-01

    Hemophagocytic lymphohistiocytosis (HLH) was originally described as a genetic disorder of immune regulation, presenting in neonates with protracted fever, hepatosplenomegaly, and cytopenia. A secondary form of HLH, triggered by serious infections, was subsequently described in adults. We report three adult patients who presented with systemic inflammatory response syndrome and features consistent with severe sepsis and septic shock, who subsequently received a diagnosis of secondary HLH. We reviewed the relationship between infection-triggered HLH and septic shock from the perspective of the adult intensivist. The hyperinflammatory pathophysiologic characteristics of HLH and septic shock are closely intertwined. Clinical and laboratory features of HLH and septic shock overlap in some patients, making the syndromes difficult to distinguish. In our experience and review, progressive pancytopenia was the feature most likely to suggest secondary HLH in the adult patient with presumed (or definite) septic shock. Use of other HLH-2004 diagnostic criteria is hindered by the poor operating characteristics of these tests in critically ill adults. Bone marrow aspiration is the most useful diagnostic test, but may yield an initial false-negative result. The HLH-2004 treatment protocol is not of proven benefit in critically ill adults, but observational data suggest that aggressive immunosuppressive therapy should not be delayed. Further study of HLH in the critical care setting might provide important insights into the pathogenesis and clinical treatment of sepsis.

  18. 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.

  19. Amyloidosis and auto-inflammatory syndromes.

    PubMed

    Grateau, Gilles; Jéru, Isabelle; Rouaghe, Saad; Cazeneuve, Cécile; Ravet, Nathalie; Duquesnoy, Philippe; Cuisset, Laurence; Dodé, Catherine; Delpech, Marc; Amselem, Serge

    2005-02-01

    Amyloidosis remains currently a severe potential complication of many chronic inflammatory disorders. It is not exactly know why some patients develop a progressive amyloidosis, whereas others do not although latent deposits may be present. A permanent acute phase response, ideally evaluated with serial measurement of serum protein SAA, the precursor of the AA protein deposited in tissues, seems to be a prerequisite to the development of inflammatory (AA) amyloidosis. Genetic factors have however been recently emphasized. Among persistent or emerging causes of AA amyloidosis, hereditary periodic fever syndromes also known as auto-inflammatory syndromes are a group of diseases characterised by intermittent bouts of clinical inflammation with focal organ involvement mainly: abdomen, musculoskeletal system and skin. The most frequent is familial Mediterranean fever which affects patients of Mediterranean descent all over the world. Three other types have been recently clinically as well as genetically characterised. A thorough diagnosis is warranted, as clinical and therapeutic management is specific for each of these diseases.

  20. Case report: severe reversible cardiomyopathy associated with systemic inflammatory response syndrome in the setting of diabetic hyperosmolar hyperglycemic non-ketotic syndrome.

    PubMed

    Berk, Justin; Wade, Raymond; Baser, Hatice Duygu; Lado, Joaquin

    2015-10-14

    This case study features a woman who presented with clinical and laboratory findings consistent with hyperosmolar hyperglycemic non-ketotic syndrome (HHNS), systemic inflammatory response syndrome (SIRS), and non-thyroidal illness syndrome (NTIS) who was noted to have a transient decrease in myocardial function. To our knowledge, this is the first case discussing the overlapping pathophysiological mechanisms could increase susceptibility to SIRS-induced cardiomyopathy. It is imperative that this clinical question be investigated further as such a relationship may have significant clinical implications for prevention and future treatments, particularly in patients similar to the one presented in this clinical case. A 53-year old Caucasian female presented to the Emergency Department for cough, nausea, vomiting and "feeling sick for 3 weeks." Labs were indicative of diabetic ketoacidosis. Initial electrocardiograms were suggestive of possible myocardial infarction and follow-up echocardiogram showed severely depressed left ventricular systolic function which resolved upon treatment of ketoacidosis. We suggest that her cardiomyopathy could have three synergistic sources: SIRS, HHNS and NTIS. Overlapping mechanisms suggest uncontrolled diabetes mellitus and NTIS could increase susceptibility to SIRS-induced cardiomyopathy as seen in this case. HHNS and SIRS cause cardiac tissue injury through mechanisms including impairment of fatty acid oxidation and formation of reactive oxygen species, as well as modifying the function of membrane calcium channels. As a result, it is conceivable that diabetes may amplify the deleterious effects of inflammatory stressors on cardiac myocytes. This novel case report offers a path for future research into prevention and treatment of SIRS-induced cardiomyopathy in, but not exclusive to, the setting of diabetes.

  1. The impact of body mass index on the development of systemic inflammatory response syndrome and sepsis in patients with polytrauma.

    PubMed

    Mica, Ladislav; Vomela, Jindřich; Keel, Marius; Trentz, Otmar

    2014-01-01

    Obesity is a growing problem in industrial nations. Our aim was to examine how overweight patients coped with systemic inflammatory response syndrome (SIRS) after polytrauma. A total of 651 patients were included in this retrospective study, with an ISS ≥ 16 and age ≥ 16 years. The sample was subdivided into three groups: body mass index (BMI; all in kg/m(2))<25, BMI 25-30 and BMI>30, or low, intermediate and high BMI. The SIRS score was measured over 31 days after admission together with measurements of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT). Data are given as the mean ± SEM if not otherwise indicated. Kruskal-Wallis and χ(2) tests were used for statistical analysis and the significance level was set at p<.05. The maximum SIRS score was reached in the low BMI-group at 3.4 ± 0.4, vs. 2.3 ± 0.1 and 2.5 ± 0.2 in the intermediate BMI-group and high BMI-group, respectively (p<.0001). However, the maximum SIRS score was reached earlier in the BMI 25-30 group at 1.8 ± 0.2 days, vs. 3.4 ± 0.4 and 2.5 ± 0.2 days in the BMI<25 and BMI>30 groups, respectively (p<.0001). The incidence of sepsis was significantly higher in the low BMI group at 46.1%, vs. 0.2% and 0% in the BMI 25-30 and BMI>30 groups, respectively (p<.0001). No significant differences in the CRP, IL-6 or PCT levels were found between groups. A higher BMI seemed to be protective for these patients with polytrauma-associated inflammatory problems. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Fresh frozen plasma is permissive for systemic inflammatory response syndrome, infection, and sepsis in multiple-injured patients.

    PubMed

    Mica, Ladislav; Simmen, Hanspeter; Werner, Clément M L; Plecko, Michael; Keller, Catharina; Wirth, Stefan H; Sprengel, Kai

    2016-08-01

    The correction of coagulopathy with fresh frozen plasma (FFP) is one of the main issues in the treatment of multiple-injured patients. Infectious and septic complications contribute to an adverse outcome in multiple-injured patients. Here, we investigated the role of FFP in the development of inflammatory complications given within the first 48 hours. A total of 2033 patients with multiple injuries and an Injury Severity Score greater than 16 points and aged 16 years or older were included. The population was subdivided into 2 groups: those who received FFP and those who did not. The data were analyzed using SPSS version 22.0. Associations between the data were tested using Pearson correlation. Independent predictivity was analyzed by binary logistic regression and multivariate regression. Data were considered as significant if P<.05. The prothrombin time at admission was significantly lower (68.5%±23.3% vs 81.8%±21.0% normal; P<.001) in the group receiving FFP. The application of FFP led to a more severe systemic inflammatory response syndrome (SIRS) grade (3.0±1.2 vs 2.2±1.4; P<.001), to a higher infection rate (48% vs 28%; P<.001), and to a higher sepsis rate (29% vs 13%; P<.001) in the patients receiving FFP. The correlations between SIRS and the incidence of infections and sepsis increased with the amount of FFP applied (P<.001). Treatment with FFP of bleeding patients with multiple injuries enhances the risk of SIRS, infection, and sepsis; however, a multifactorial genesis has to be postulated. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Trauma, Systemic Inflammatory Response Syndrome, Dietary Supplements, Illicit Steroid Use and a Questionable Malignant Hyperthermia Reaction

    PubMed Central

    Capacchione, John F.; Radimer, Matthew C.; Sagel, Jeffrey S.; Kraus, Gregory P.; Sambuughin, Nyamkhishig; Muldoon, Sheila M.

    2009-01-01

    BACKGROUND Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated primarily, but not exclusively, with mutations in the skeletal muscle ryanodine receptor. Associated environmental factors, however, may also be important for expression of the syndrome. METHODS AND RESULTS A 24-yr-old trauma patient developed a fulminant MH crisis after a 3 minute exposure to sevoflurane. A thorough evaluation of underlying co-morbidities revealed a number of environmental factors that could have altered skeletal muscle calcium regulation, and may have potentially influenced the effects of volatile inhaled anesthetics. Since MH is a syndrome characterized by abnormal skeletal muscle calcium regulation, other factors that alter calcium homeostasis may exacerbate the impact of inhaled MH-triggering drugs. CONCLUSIONS While a thorough history of MH episodes in a proband and family is emphasized as part of a complete preanesthetic evaluation, obtaining a history of other environmental entities that may alter calcium regulation may be equally important to knowing the family history. PMID:19224800

  4. Evaluation of the systemic inflammatory response syndrome criteria for the diagnosis of sepsis due to maternal bacteremia.

    PubMed

    Maguire, Patrick J; Power, Karen A; Downey, Andrew F; O'Higgins, Amy C; Sheehan, Sharon R; Turner, Michael J

    2016-04-01

    To examine, in the setting of maternal bacteremia, the implications for the diagnosis of maternal sepsis of customizing the systemic inflammatory response syndrome (SIRS) criteria for physiologic changes of pregnancy. Women with maternal bacteremia in a tertiary maternity hospital during 2009-2014 were identified. Records were retrospectively reviewed to determine whether they fulfilled the criteria for diagnosis of sepsis based on either the standard SIRS parameters derived from the Surviving Sepsis Campaign or SIRS parameters customized for pregnancy. Diagnosis of sepsis was based on the presence of two or more SIRS criteria, in conjunction with infection, during the hour before and the 6 hours after phlebotomy for blood culture. Of 93 women with bacteremia, 61 (66%) would have been diagnosed with sepsis based on standard criteria compared with 52 (56%) based on customized criteria (P=0.18). Seventeen women had a diagnosis of sepsis based on the standard but not the customized criteria, while eight women had sepsis based on the customized but not the standard criteria. In maternal bacteremia, customized SIRS criteria do not increase the rate of diagnosis of sepsis. Prospective studies should investigate whether the introduction of customized SIRS criteria can improve clinical outcomes. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Comparison of surgical outcome and the systemic inflammatory response syndrome score between retroperitoneoscopic hand-assisted nephroureterectomy and open nephroureterectomy.

    PubMed

    Sato, Yoshikazu; Nanbu, Akihito; Tanda, Hitoshi; Kato, Shuji; Onishi, Shigeki; Nakajima, Hisao; Nitta, Toshikazu; Koroku, Mikio; Akagashi, Keigo; Hanzawa, Tatsuo

    2006-12-01

    The goal of this study is to compare surgical and oncological outcomes of laparoscopic nephroureterectomy and the open surgery using the concept of systemic inflammatory response syndrome (SIRS) in addition to common variables. Thirty-six and 23 patients having upper urinary tract urothelial cancer who were operated on with retroperitoneoscopic hand-assisted nephroureterectomy (RHANU) or standard open nephroureterectomy (ONU) retrospectively, were analyzed. Median operation time was 140 (range 70-200) and 60 (range 45-85) minutes, respectively in the RHANU group and the ONU group. The median days to ambulation and hospital stay of the RHANU group were significantly shorter than those of the ONU group. There was no significant difference in the incidence of SIRS and other surgical results between the two groups. In oncological outcome, no significant difference was found in the bladder recurrence rate (RHANU vs. ONU; 52% vs. 45%), local recurrence (0% vs. 0%), distant metastasis (11% vs. 13%) or survival rate (94% vs. 91%) between the RHANU group and the ONU group at 2-year follow-up. There was no port site recurrence in the RHANU group. Although the RHANU may have an advantage in terms of earlier recovery, there were no significant differences in the incidence of SIRS and oncological outcomes between the RHANU group and the ONU group.

  6. Auto-inflammatory syndromes and oral health.

    PubMed

    Scully, C; Hodgson, T; Lachmann, H

    2008-11-01

    Auto-inflammatory diseases (periodic syndromes) are rare childhood-onset disorders which are characterized by fluctuating or recurrent episodes of fever and inflammation affecting serosal surfaces, joints, eyes and/or skin without significant autoantibody production or an identifiable underlying infection. They are disorders of innate immunity and the underlying genetic defect has been identified in most of the syndromes. Diagnosis relies on clinical symptoms and evidence of an elevated acute phase response during attacks, supported by finding mutations in the relevant genes. Several syndromes can lead to systemic AA amyloidosis. Aphthous-like oral ulceration has been reported as one manifestation in several of the syndromes, including periodic fever, aphthous-stomatitis, pharyngitis, adenitis (PFAPA) familial Mediterranean fever (FMF), hyperimmunoglobulinaemia D and periodic fever syndrome, tumour necrosis factor receptor associated periodic syndrome and pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA). Chronic jaw recurrent osteomyelitis has been recorded in chronic recurrent multifocal osteomyelitis. Advances in the molecular pathogenesis of these syndromes and the regulation of innate immunity have enhanced diagnosis, and rationalized therapies. This article reviews the periodic fever syndromes relevant to oral health and the suggested association of FMF with Behçet's disease.

  7. Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis.

    PubMed

    Silversides, Jonathan A; Ferguson, Andrew J; McAuley, Daniel F; Blackwood, Bronagh; Marshall, John C; Fan, Eddy

    2015-11-12

    Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness. We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate. While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials. PROSPERO CRD42013005608. ( http://www.crd.york.ac.uk/PROSPERO/ ).

  8. Selenium, copper, zinc, iron levels and mortality in patients with sepsis and systemic inflammatory response syndrome in Western Black Sea Region, Turkey.

    PubMed

    Ayoglu, Hilal; Sezer, Ustun; Akin, Mehmet; Okyay, Dilek; Ayoglu, Ferruh; Can, Murat; Kucukosman, Gamze; Piskin, Ozcan; Aydin, Bengu; Cimencan, Murat; Gur, Abdullah; Turan, Isil

    2016-04-01

    To evaluate the changing levels of selenium, copper, zinc and iron in patients with sepsis and systemic inflammatory response syndrome and their influence on mortality. The prospective study was conducted at a tertiary care university hospital in Zonguldak city in the western Black Sea region of Turkey from January 2012 to December 2013, and comprised patients with sepsis and systemic inflammatory response syndrome. Blood samples were taken on 1st, 3rd, 5th and 7th days to measure serum selenium, copper, zinc and iron levels. Patients' demographic data, presence of additional diseases and mortality were recorded. Of the 57 patients, 28(49.1%) were female and 29(50.9%) were male, with an overall mean age of 60.3±19.4 years, mean height of 166.1±11.4cm, mean weight of 76.5±17.5kg. Copper and zinc levels were in the normal range, while selenium and iron levels were lower than the limit values at all measuring periods. There was no significant difference between first and other days in accordance with element levels (p>0.05). Baseline copper levels in patients with malignancy were lower than patients without malignancy (p< 0.05). In hypertensive patients, baseline copper levels were higher and 7th day levels were lower than non-hypertensive (p< 0.05). Baseline selenium levels of those who died were lower than the other patients (p< 0.05). Selenium and iron levels were decreased in patients with sepsis-systemic inflammatory response syndrome and copper levels were lower in patients with malignancy, hypertension and chronic obstructive pulmonary disease (p< 0.05). There was no change in zinc levels of the patients. Reduced basal selenium levels of patients with sepsis and systemic inflammatory response syndrome were associated with mortality.

  9. The prevalence and diagnostic utility of systemic inflammatory response syndrome vital signs in a pediatric emergency department.

    PubMed

    Scott, Halden F; Deakyne, Sara J; Woods, Jason M; Bajaj, Lalit

    2015-04-01

    This study sought to determine the prevalence, test characteristics, and severity of illness of pediatric patients with systemic inflammatory response syndrome (SIRS) vital signs among pediatric emergency department (ED) visits. This was a retrospective descriptive cohort study of all visits to the ED of a tertiary academic free-standing pediatric hospital over 1 year. Visits were included if the patient was <18 years of age and did not leave before full evaluation or against medical advice. Exclusion criteria were trauma diagnoses or missing documentation of vital signs. Data were electronically extracted from the medical record. The primary predictor was presence of vital signs meeting pediatric SIRS definitions. Specific vital sign pairs comprising SIRS were evaluated as predictors (temperature-heart rate, temperature-respiratory rate, and temperature-corrected heart rate, in which a formula was used to correct heart rate for degree of temperature elevation). The primary outcome measure was requirement for critical care (receipt of a vasoactive agent or intubation) within 24 hours of ED arrival. There were 56,210 visits during the study period; 40,356 met inclusion criteria. Of these, 6,596 (16.3%) visits had fever >38.5°C, and 6,122 (15.2% of included visits) met SIRS vital sign criteria. Among included visits, those with SIRS vital signs accounted for 92.8% of all visits with fever >38.5°C. Among patients with SIRS vital signs, 4993 (81.6%) were discharged from the ED without intravenous (IV) therapy and without 72-hour readmission. Critical care within the first 24 hours was present in 99 (0.25%) patients: 23 patients with and 76 without SIRS vital signs. Intensive care unit (ICU) admission was present in 126 (2.06%) with SIRS vital signs and 487 (1.42%) without SIRS vital signs. SIRS vital signs were associated with increased risk of critical care within 24 hours (relative risk [RR] = 1.69, 95% confidence interval [CI] = 1.06 to 2.70), ICU admission (RR

  10. Temperature variability analysis using wavelets and multiscale entropy in patients with systemic inflammatory response syndrome, sepsis, and septic shock

    PubMed Central

    2012-01-01

    Background Even though temperature is a continuous quantitative variable, its measurement has been considered a snapshot of a process, indicating whether a patient is febrile or afebrile. Recently, other diagnostic techniques have been proposed for the association between different properties of the temperature curve with severity of illness in the Intensive Care Unit (ICU), based on complexity analysis of continuously monitored body temperature. In this study, we tried to assess temperature complexity in patients with systemic inflammation during a suspected ICU-acquired infection, by using wavelets transformation and multiscale entropy of temperature signals, in a cohort of mixed critically ill patients. Methods Twenty-two patients were enrolled in the study. In five, systemic inflammatory response syndrome (SIRS, group 1) developed, 10 had sepsis (group 2), and seven had septic shock (group 3). All temperature curves were studied during the first 24 hours of an inflammatory state. A wavelet transformation was applied, decomposing the signal in different frequency components (scales) that have been found to reflect neurogenic and metabolic inputs on temperature oscillations. Wavelet energy and entropy per different scales associated with complexity in specific frequency bands and multiscale entropy of the whole signal were calculated. Moreover, a clustering technique and a linear discriminant analysis (LDA) were applied for permitting pattern recognition in data sets and assessing diagnostic accuracy of different wavelet features among the three classes of patients. Results Statistically significant differences were found in wavelet entropy between patients with SIRS and groups 2 and 3, and in specific ultradian bands between SIRS and group 3, with decreased entropy in sepsis. Cluster analysis using wavelet features in specific bands revealed concrete clusters closely related with the groups in focus. LDA after wrapper-based feature selection was able to classify

  11. Systemic inflammatory response syndrome-based severe sepsis screening algorithms in emergency department patients with suspected sepsis.

    PubMed

    Shetty, Amith L; Brown, Tristam; Booth, Tarra; Van, Kim Linh; Dor-Shiffer, Daphna E; Vaghasiya, Milan R; Eccleston, Cassanne E; Iredell, Jonathan

    2016-06-01

    Systemic inflammatory response syndrome (SIRS)-based severe sepsis screening algorithms have been utilised in stratification and initiation of early broad spectrum antibiotics for patients presenting to EDs with suspected sepsis. We aimed to investigate the performance of some of these algorithms on a cohort of suspected sepsis patients. We conducted a retrospective analysis on an ED-based prospective sepsis registry at a tertiary Sydney hospital, Australia. Definitions for sepsis were based on the 2012 Surviving Sepsis Campaign guidelines. Numerical values for SIRS criteria and ED investigation results were recorded at the trigger of sepsis pathway on the registry. Performance of specific SIRS-based screening algorithms at sites from USA, Canada, UK, Australia and Ireland health institutions were investigated. Severe sepsis screening algorithms' performance was measured on 747 patients presenting with suspected sepsis (401 with severe sepsis, prevalence 53.7%). Sensitivity and specificity of algorithms to flag severe sepsis ranged from 20.2% (95% CI 16.4-24.5%) to 82.3% (95% CI 78.2-85.9%) and 57.8% (95% CI 52.4-63.1%) to 94.8% (95% CI 91.9-96.9%), respectively. Variations in SIRS values between uncomplicated and severe sepsis cohorts were only minor, except a higher mean lactate (>1.6 mmol/L, P < 0.01). We found the Ireland and JFK Medical Center sepsis algorithms performed modestly in stratifying suspected sepsis patients into high-risk groups. Algorithms with lactate levels thresholds of >2 mmol/L rather than >4 mmol/L performed better. ED sepsis registry-based characterisation of patients may help further refine sepsis definitions of the future. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  12. Biomarkers in critically ill patients with systemic inflammatory response syndrome or sepsis supplemented with high-dose selenium.

    PubMed

    Brodska, Helena; Valenta, Jiri; Malickova, Karin; Kohout, Pavel; Kazda, Antonin; Drabek, Tomas

    2015-01-01

    Low levels of selenium (Se) and glutathione peroxidase (GSHPx), a key selenoenzyme, were documented in systemic inflammatory response syndrome (SIRS) and sepsis, both associated with high mortality. Se supplementation had mixed effects on outcome. We hypothesized that Se supplementation could have a different impact on biomarkers and 28-day mortality in patients with SIRS vs. sepsis. Adult patients with SIRS or sepsis were randomized to either high-dose (Se+, n = 75) or standard-dose (Se-, n = 75) Se supplementation. Plasma Se, whole blood GSHPx activity, C-reactive protein (CRP), procalcitonin (PCT), prealbumin, albumin and cholesterol levels were measured serially up to day 14. There was no difference in mortality between Se- (24/75) vs. Se+ group (19/75; p = 0.367) or between SIRS and septic patients (8/26 vs. 35/124; p = 0.794). There was a trend to reduced mortality in SIRS patients in the Se+ vs. Se- group (p = 0.084). Plasma Se levels increased in the Se+ group only in patients with sepsis but not in patients with SIRS. Plasma Se levels correlated with GSHPx. In SIRS/Se+ group, Se correlated only with GSHPx. In SIRS/Se- group, Se correlated with cholesterol but not with other biomarkers. In sepsis patients, Se levels correlated with cholesterol, GSHPx and prealbumin. Cholesterol levels were higher in survivors in the Se- group. Se levels correlated with GSHPx activity and other nutritional biomarkers with significant differences between SIRS and sepsis groups. High-dose Se supplementation did not affect mortality but a strong trend to decreased mortality in SIRS patients warrants further studies in this population. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. Platelet-to-Lymphocyte Ratio: A New Factor for Predicting Systemic Inflammatory Response Syndrome after Percutaneous Nephrolithotomy.

    PubMed

    Cetinkaya, Mehmet; Buldu, Ibrahim; Kurt, Omer; Inan, Ramazan

    2017-08-29

    The first purpose of this study was to reveal factors affecting the postoperative development of systemic inflammatory response syndrome (SIRS) in patients undergoing standard percutaneous nephrolithotomy (PNL) for renal stones. The second purpose was to determine the role of the preoperative platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) in the prediction of SIRS.Matarials and Methods: In total, 192 patients who had undergone conventional PNL for renal stones from 2013 to 2015 were included in the study. SIRS developed postoperatively in 41 (21.3%) patients. The patients were divided into SIRS and non-SIRS groups, and the effects of the PLR, NLR, and other demographic and operative data were investigated to predict the development of SIRS. Variables significant in the univariate analysis were evaluated using a multiple logistic regression model to determine the independent risk factors for developing SIRS after PNL. Univariate analysis revealed significant differences in the preoperative PLR (P < .001), preoperative NLR (P = .018), number of access sites (P < .001), mean renal parenchymal thickness (P = .02), operative time (P < .001), decrease in hemoglobin (P = .016), length of hospital stay (P < .001), stone-free status (P = .023), and complication rate between the two groups of patients. However, multivariate analysis showed that only the PLR and the number of access sites were independent factors affecting the development of SIRS. When the PLR cut-off value was 114.1, development of SIRS was predicted with 80.4% sensitivity and 60.2% specificity. The preoperative PLR is an effective and inexpensive biomarker with which to predict SIRS after PNL. In particular, we recommend close monitoring of patients with a PLR of >114.1 because of the possibledevelopment of serious complications.

  14. Neutrophil apoptosis is delayed in an equine model of colitis: Implications for the development of systemic inflammatory response syndrome.

    PubMed

    Anderson, S L; Singh, B

    2017-05-01

    Horses that develop colitis invariably exhibit signs of a systemic inflammatory response syndrome (SIRS). A significant contributor to the development of SIRS in human subjects is delayed neutrophil apoptosis, but this has not been specifically studied in horses. To determine the occurrence of ex vivo neutrophil apoptosis and its contribution to the development of SIRS in an equine colitis model. Experiment using a colitis model. Neutrophils were isolated before and after the induction of colitis using an oligofructose overdose model, placed into culture for 12 h or 24 h with or without lipopolysaccharide (LPS) at various concentrations, and assessed for the occurrence of apoptosis using Annexin V and propidium iodide staining with flow cytometric quantification. Levels of caspase-3, -8 and -9 activity were measured after 12 h of incubation in neutrophil lysates. Ex vivo neutrophil apoptosis was significantly delayed in neutrophils isolated after the induction of colitis (12-h incubation: P = 0.004; 24-h incubation: P = 0.003) with concomitant reductions in caspase-3, -8 and -9 activity (caspase-3: P = 0.004; caspase-8: P = 0.02; caspase-9: P = 0.02). Neutrophils isolated after the induction of colitis were refractory to LPS-delayed apoptosis. Neutrophil apoptosis was delayed with increasing cell concentration in vitro. The main limitation of the study is the that the exact mechanism for delayed neutrophil apoptosis following the induction of colitis was not fully elucidated. The data show that neutrophil apoptosis is delayed in horses following the induction of colitis as a result of interference with the intrinsic and extrinsic apoptotic pathways, which may contribute to the development of equine SIRS. Concurrent development of neutrophilia may contribute to a prolonged neutrophil lifespan through a concentration-dependent delay in apoptosis. © 2016 EVJ Ltd.

  15. The sterile inflammatory response.

    PubMed

    Rock, Kenneth L; Latz, Eicke; Ontiveros, Fernando; Kono, Hajime

    2010-01-01

    The acute inflammatory response is a double-edged sword. On the one hand, it plays a key role in initial host defense, particularly against many infections. On the other hand, its aim is imprecise, and as a consequence, when it is drawn into battle, it can cause collateral damage in tissues. In situations where the inciting stimulus is sterile, the cost-benefit ratio may be high; because of this, sterile inflammation underlies the pathogenesis of a number of diseases. Although there have been major advances in our understanding of how microbes trigger inflammation, much less has been learned about this process in sterile situations. This review focuses on a subset of the many sterile stimuli that can induce inflammation-specifically dead cells and a variety of irritant particles, including crystals, minerals, and protein aggregates. Although this subset of stimuli is structurally very diverse and might appear to be unrelated, there is accumulating evidence that the innate immune system may recognize them in similar ways and stimulate the sterile inflammatory response via common pathways. Here we review established and emerging data about these responses.

  16. Systemic inflammatory response syndrome is more associated with bacteremia in elderly patients with suspected sepsis in emergency departments.

    PubMed

    Chou, Hsien-Ling; Han, Shih-Tsung; Yeh, Chun-Fu; Tzeng, I-Shaing; Hsieh, Tsung-Han; Wu, Chin-Chieh; Kuan, Jen-Tse; Chen, Kuan-Fu

    2016-12-01

    Early diagnosis of bacteremia for patients with suspected sepsis is 1 way to improve prognosis of sepsis. Systemic inflammatory response syndrome (SIRS) has long been utilized as a screening tool to detect bacteremia by front-line healthcare providers. The value of SIRS to predict bacteremia in elderly patients (≥65 years) with suspected sepsis has not yet been examined in emergency departments (EDs).We aimed to evaluate the performance of SIRS components in predicting bacteremia among elderly patients in EDs.We retrospectively evaluated patients with suspected sepsis and 2 sets of blood culture collected within 4 hours after admitting to ED in a tertiary teaching hospital between 2010 and 2012. Patients were categorized into 3-year age groups: young (18-64 years), young-old (65-74 years), and old patients (≥75 years). Vital signs and Glasgow Coma Scale with verbal response obtained at the triage, comorbidities, sites of infection, blood cultures, and laboratory results were retrieved via the electronic medical records.A total of 20,192 patients were included in our study. Among them, 9862 (48.9%) were the elderly patients (young-old and old patients), 2656 (13.2%) developed bacteremia. Among patients with bacteremia, we found the elderly patients had higher SIRS performance (adjusted odds ratio [aOR]: 2.40, 95% confidence interval [CI]: 1.90-3.03 in the young-old and aOR: 2.66, 95% CI: 2.19-3.23 in the old). Fever at the triage was most predictive of bacteremia, especially in the elderly patients (aOR: 2.19, 95% CI: 1.81-2.65 in the young-old and aOR: 2.27, 95% CI: 1.95-2.63 in the old), and tachypnea was not predictive of bacteremia among the elderly patients (all P > 0.2).The performance of SIRS to predict bacteremia was more suitable for elderly patients in EDs observed in this study. The elderly patients presented with more fever and less tachypnea when they had bacteremia.

  17. Systemic inflammatory response syndrome is more associated with bacteremia in elderly patients with suspected sepsis in emergency departments

    PubMed Central

    Chou, Hsien-Ling; Han, Shih-Tsung; Yeh, Chun-Fu; Tzeng, I-Shaing; Hsieh, Tsung-Han; Wu, Chin-Chieh; Kuan, Jen-Tse; Chen, Kuan-Fu

    2016-01-01

    Abstract Early diagnosis of bacteremia for patients with suspected sepsis is 1 way to improve prognosis of sepsis. Systemic inflammatory response syndrome (SIRS) has long been utilized as a screening tool to detect bacteremia by front-line healthcare providers. The value of SIRS to predict bacteremia in elderly patients (≥65 years) with suspected sepsis has not yet been examined in emergency departments (EDs). We aimed to evaluate the performance of SIRS components in predicting bacteremia among elderly patients in EDs. We retrospectively evaluated patients with suspected sepsis and 2 sets of blood culture collected within 4 hours after admitting to ED in a tertiary teaching hospital between 2010 and 2012. Patients were categorized into 3-year age groups: young (18–64 years), young-old (65–74 years), and old patients (≥75 years). Vital signs and Glasgow Coma Scale with verbal response obtained at the triage, comorbidities, sites of infection, blood cultures, and laboratory results were retrieved via the electronic medical records. A total of 20,192 patients were included in our study. Among them, 9862 (48.9%) were the elderly patients (young-old and old patients), 2656 (13.2%) developed bacteremia. Among patients with bacteremia, we found the elderly patients had higher SIRS performance (adjusted odds ratio [aOR]: 2.40, 95% confidence interval [CI]: 1.90–3.03 in the young-old and aOR: 2.66, 95% CI: 2.19–3.23 in the old). Fever at the triage was most predictive of bacteremia, especially in the elderly patients (aOR: 2.19, 95% CI: 1.81–2.65 in the young-old and aOR: 2.27, 95% CI: 1.95–2.63 in the old), and tachypnea was not predictive of bacteremia among the elderly patients (all P > 0.2). The performance of SIRS to predict bacteremia was more suitable for elderly patients in EDs observed in this study. The elderly patients presented with more fever and less tachypnea when they had bacteremia. PMID:27930596

  18. A role for leptin in the systemic inflammatory response syndrome (SIRS) and in immune response, an update.

    PubMed

    Waelput, W; Brouckaert, P; Broekaert, D; Tavernier, J

    2006-01-01

    Leptin was originally identified as an adipocyte-derived cytokine with a key role in the regulation of the energy balance. Subsequent research revealed that leptin's biological action is not restricted to its effects on appetite and food intake, but instead has a much more pleiotropic character. There is now ample evidence that leptin has important functions in reproduction, hematopoiesis, HPA-axis endocrinology and angiogenesis. In this review we have focused on the effects of leptin in the antigen-specific immunity and in the inflammatory effector system.

  19. Change of teicoplanin loading dose requirement for incremental increases of systemic inflammatory response syndrome score in the setting of sepsis.

    PubMed

    Nakano, Takafumi; Nakamura, Yoshihiko; Takata, Tohru; Irie, Keiichi; Sano, Kazunori; Imakyure, Osamu; Mishima, Kenichi; Futagami, Koujiro

    2016-08-01

    Background Target trough concentrations are recommended for teicoplanin (TEIC) to minimize its adverse effects and to maximize efficacy in sepsis caused by grampositive cocci, including methicillin-resistant Staphylococcus aureus infection. However, optimal doses to attain proper trough values in patients with sepsis have not yet been well established for TEIC. Objective This study investigated whether the systemic inflammatory response syndrome (SIRS) score could predict the pharmacokinetics of TEIC in patients with sepsis. Setting This study was conducted at Fukuoka University Hospital in Japan. Methods We retrospectively reviewed the records of patients using TEIC between April 2012 and March 2015. SIRS positive was defined as infection with a SIRS score ≥2. Estimates of pharmacokinetic parameters were calculated using a Bayesian method. Creatinine clearance rates were estimated by the Cockcroft-Gault formula (eCcr). Main outcome measure Change of TEIC loading dose requirement for incremental increases of SIRS score. Results In total, 133 patients were enrolled: 50 non-SIRS patients and 83 patients with SIRS. The TEIC plasma trough concentration was significantly lower in SIRS than non-SIRS patients (15.7 ± 7.1 vs. 20.1 ± 8.6 μg/mL; P < 0.01), although there was no significant difference in the loading dose administered. Moreover, SIRS scores were increasingly predictive of eCcr and TEIC clearance in a stepwise manner. To achieve the target trough concentration (15-30 μg/mL), the optimal doses required in non-SIRS versus SIRS patients were 12-24 versus 18-30 mg/kg/day, respectively, during the first 48 h. Conclusions These findings suggest that the pharmacokinetics of TEIC are altered in SIRS patients, who required higher doses than non-SIRS patients to achieve the target trough concentration. We suggest that the SIRS score can become a new modality to determine the initial TEIC loading dose.

  20. Extracellular phospholipases A2 in relation to systemic inflammatory response syndrome (SIRS) and systemic complications in severe acute pancreatitis.

    PubMed

    Hietaranta, A; Kemppainen, E; Puolakkainen, P; Sainio, V; Haapiainen, R; Peuravuori, H; Kivilaakso, E; Nevalainen, T

    1999-05-01

    The pathophysiology of severe acute pancreatitis (AP) resembles other conditions with systemic inflammatory response syndrome (SIRS) such as sepsis predisposing to remote organ failure. Because extracellular phospholipases A2 (PLA2) have been implicated in AP, their serum concentrations were analyzed with respect to SIRS and systemic complications in patients with severe AP. The serum samples were collected daily for 12 days in 57 patients with severe AP. SIRS, early organ complications, local complications, and outcome of AP were recorded. Time-resolved fluoroimmunoassays were used for group I and group II PLA2 measurements. Thirty-nine (68.4%) patients fulfilled the criteria of SIRS within 12 days from admission. Pancreatic necrosis was detected in 43 (75.4%) patients. Infected necrosis was found preoperatively or at operation in five (8.8%) patients. Twenty-six (45.6%) and eight (14.0%) patients had respiratory or renal failure, respectively. Seven (12.3%) patients died of their disease. All patients with systemic complications fulfilled the criteria of SIRS. The increasing number of positive SIRS criteria was associated with increased frequency of systemic complications. Pancreatic necrosis was not significantly associated with SIRS. The serum concentration of group II PLA2 was significantly higher in patients with SIRS (p < 0.05) compared with patients without from day 7 onward. The concentration of group II PLA2 increased (p < 0.01) in patients with SIRS but decreased in patients without. The serum concentration of group II PLA2 did not differ significantly with respect to systemic complications. The concentration of group I PLA2 decreased (p < 0.05) similarly in patients with and without SIRS or systemic complications during follow-up, respectively. Early systemic complications of severe AP are associated with SIRS with increasing frequency as the number of positive SIRS criteria increases. Group II PLA2 but not group I PLA2 may have pathophysiologic

  1. The inflammatory response in sepsis.

    PubMed

    Bosmann, Markus; Ward, Peter A

    2013-03-01

    The pathophysiology of sepsis and its accompanying systemic inflammatory response syndrome (SIRS) and the events that lead to multiorgan failure and death are poorly understood. It is known that, in septic humans and rodents, the development of SIRS is associated with a loss of the redox balance, but SIRS can also develop in noninfectious states. In addition, a hyperinflammatory state develops, together with impaired innate immune functions of phagocytes, immunosuppression, and complement activation, collectively leading to septic shock and lethality. Here, we discuss recent insights into the signaling pathways in immune and phagocytic cells that underlie sepsis and SIRS and consider how these might be targeted for therapeutic interventions to reverse or attenuate pathways that lead to lethality during sepsis.

  2. The Inflammatory Response in Sepsis

    PubMed Central

    Bosmann, Markus; Ward, Peter A.

    2012-01-01

    The pathophysiology of sepsis and its accompanying systemic inflammatory response syndrome (SIRS) and the events that lead to multiorgan failure and death are poorly understood. It is known that, in septic humans and rodents, the development of SIRS is associated with a loss of the redox balance, but SIRS can also develop in non-infectious states. In addition, a hyperinflammatory state develops, together with impaired innate immune functions of phagocytes, immunosuppression, and complement activation, collectively leading to septic shock and lethality. Here we discuss recent insights into the signaling pathways in immune and phagocytic cells that underlie sepsis and SIRS and consider how these might be targeted for therapeutic interventions to reverse or attenuate pathways that lead to lethality during sepsis. PMID:23036432

  3. Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF -238A polymorphism.

    PubMed

    Pappachan, John V; Coulson, Tim G; Child, Nicholas J A; Markham, David J; Nour, Sarah M; Pulletz, Mark C K; Rose-Zerilli, Matthew J; de Courcey-Golder, Kim; Barton, Sheila J; Yang, Ian A; Holloway, John W

    2009-10-01

    The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5' nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF -238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF -238A was significantly higher in patients who died in ICU compared to those who survived (p = 0.0063) as was the frequency of the two haplotypes LTA +252G, TNF -1031T, TNF -308G, TNF -238A and LTA +252G, TNF-1031T, TNF-308A and TNF-238A (p = 0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity.

  4. Advances in understanding adenosine as a plurisystem modulator in sepsis and the systemic inflammatory response syndrome (SIRS).

    PubMed

    Conlon, Beth A; Ross, James D; Law, William R

    2005-09-01

    Adenosine is a ubiquitous molecule that influences every physiological system studied thus far. In this review, we consider the influence of this purine nucleoside on some of the physiological systems affected during sepsis and SIRS. In the control of perfusion and cardiac output distribution, endogenous adenosine appears to play an important role in regulating perfusion in various vascular beds. Some of this control is mediated by stimulation of adenylyl cyclase, while part occurs by stimulating the production of nitric oxide. In the heart, adenosine may act as an inhibitory modulator of TNF-alpha expression. With regard to innate immune responses the effects of adenosine vary considerably, and are complex. However, the dominant responses relevant to SIRS indicate attenuation of inflammatory responses. Many of the effects of adenosine may also involve modulating oxyradical-mediated response. This occurs via increased oxyradical production via adenosine degradation (xanthine oxidase pathway), or limiting inflammatory oxyradical generation. Attempts to exploit the beneficial responses to adenosine have met with some success, and are considered here.

  5. BLOOD pH AND GASES IN FETUSES IN PRETERM LABOR WITH AND WITHOUT SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

    PubMed Central

    Romero, Roberto; Soto, Eleazar; Berry, Stanley M.; Hassan, Sonia S.; Kusanovic, Juan Pedro; Yoon, Bo Hyun; Edwin, Samuel; Mazor, Moshe; Chaiworapongsa, Tinnakorn

    2012-01-01

    OBJECTIVE Fetal hypoxemia has been proposed to be one of the mechanisms of preterm labor (PTL) and delivery. This may have clinical implications since it may alter: 1) the method/frequency of fetal surveillance; and 2) the indications and duration of tocolysis to an already compromised fetus. The aim of this study was to examine whether there is a difference in the fetal blood gas analysis [pH, PaO2 and base excess (BE)] and in the prevalence of fetal acidemia and hypoxia between: 1) patients in PTL who delivered within 72 hours vs. those who delivered more than 72 hours after cordocentesis; and 2) patients with Fetal Inflammatory Response Syndrome (FIRS) vs. those without this condition. STUDY DESIGN Patients admitted with PTL underwent amniocentesis and cordocentesis. Ninety women with singleton pregnancies and PTL were classified according to 1) those who delivered within 72 hours (n = 30) and after 72 hours of the cordocentesis (n = 60); and 2) with and without FIRS. FIRS was defined as a fetal plasma concentration of IL-6 >11 pg/mL. Fetal blood gases were determined. Acidemia and hypoxemia were defined as fetal pH and PaO2 below the 5th percentile for gestational age, respectively. For comparisons between the two study groups, ΔpH and ΔPaO2 were calculated by adjusting for gestational age (Δ = observed value-mean for gestational age). Non-parametric statistics were employed. RESULTS No differences in the median Δ pH (−0.026 vs. −0.016), ΔPaO2 (0.25 mmHg vs. 5.9 mmHg) or BE (−2.4 mEq/L vs. −2.6 mEq/L) were found between patients with PTL who delivered within 72 hours and those who delivered 72 hours after the cordocentesis (p>0.05 for all comparisons). Fetal plasma IL-6 concentration was determined in 63% (57/90) of fetuses and the prevalence of FIRS was 28% (16/57). There was no difference in fetal pH, PaO2 and BE between fetuses with and without FIRS (p>0.05 for all comparisons). Moreover, there was no difference in the rate of fetal acidemia

  6. Immune Reconstitution Inflammatory Syndrome: Opening Pandora's Box

    PubMed Central

    2017-01-01

    One of the purposes of antiretroviral therapy (ART) is to restore the immune system. However, it can sometimes lead to an aberrant inflammatory response and paradoxical clinical worsening known as the immune reconstitution inflammatory syndrome (IRIS). We describe a 23-year-old male, HIV1 infected with a rapid progression phenotype, who started ART with TCD4+ of 53 cells/mm3 (3,3%) and HIV RNA = 890000 copies/mL (6 log). Four weeks later he was admitted to the intensive care unit with severe sepsis. The diagnostic pathway identified progressive multifocal leukoencephalopathy, digestive Kaposi sarcoma, and P. aeruginosa bacteraemia. Five weeks after starting ART, TCD4+ cell count was 259 cells/mm3 (15%) and HIV RNA = 3500 copies/mL (4 log). He developed respiratory failure and progressed to septic shock and death. Those complications might justify the outcome but its autopsy opened Pandora's box: cerebral and cardiac toxoplasmosis was identified, as well as hemophagocytic syndrome, systemic candidiasis, and Mycobacterium avium complex infection. IRIS remains a concern and eventually a barrier to ART. Male gender, young age, low TCD4 cell count, and high viral load are risk factors. The high prevalence of subclinical opportunistic diseases highlights the need for new strategies to reduce IRIS incidence. PMID:28163944

  7. Bioengineered gold nanoparticles targeted to mesenchymal cells from patients with bronchiolitis obliterans syndrome does not rise the inflammatory response and can be safely inhaled by rodents.

    PubMed

    Cova, Emanuela; Inghilleri, Simona; Pandolfi, Laura; Morosini, Monica; Magni, Sara; Colombo, Miriam; Piloni, Davide; Finetti, Chiara; Ceccarelli, Gabriele; Benedetti, Laura; Cusella, Maria Gabriella; Agozzino, Manuela; Corsi, Fabio; Allevi, Raffaele; Mrakic-Sposta, Simona; Moretti, Sarah; De Gregori, Simona; Prosperi, Davide; Meloni, Federica

    2017-05-01

    The use of gold nanoparticles (GNPs) as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long-term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favors epithelial-mesenchymal transition and activation of local mesenchymal cells (MCs) leading to airway fibro-obliteration. In a previous work, we engineered GNPs loaded with the mammalian target of rapamycin inhibitor everolimus, specifically decorated with an antibody against CD44, a surface receptor expressed by primary MCs isolated from bronchoalveolar lavage of BOS patients. We proved in vitro that these GNPs (GNP-HCe) were able to specifically inhibit primary MCs without affecting the bronchial epithelial cell. In the present work, we investigated the effect of these bioengineered nanoconstructs on inflammatory cells, given that a stimulating effect on macrophages, neutrophils or lymphocytes is strongly unwanted in graft airways since it would foster fibrogenesis. In addition, we administered GNP-HCe by the inhalatory route to normal mice for a preliminary assessment of their pulmonary and peripheral (liver, spleen and kidney) uptake. By these experiments, an evaluation of tissue toxicity was also performed. The present study proves that our bioengineered nanotools do not rise an inflammatory response and, under the tested inhalatory conditions that were used, are non-toxic.

  8. Activation of Adenosine 2A receptor inhibits neutrophil apoptosis in an autophagy-dependent manner in mice with systemic inflammatory response syndrome

    PubMed Central

    Liu, Yang-Wuyue; Yang, Ting; Zhao, Li; Ni, Zhenhong; Yang, Nan; He, Fengtian; Dai, Shuang-Shuang

    2016-01-01

    Systemic inflammatory response syndrome (SIRS) is an overwhelming whole body inflammation caused by infectious diseases or sterile insults. Neutrophils are the dominant participants during inflammation, and their survival and death determine the initiation as well as resolution of SIRS. Apoptosis and autophagy are two fundamental cellular processes that modulating cell fate, but their correlation and regulators in neutrophils under SIRS condition have not been elucidated. In this study, we demonstrated that high dose of LPS induced both apoptosis and autophagy of neutrophils in a mouse SIRS model and LPS-stimulated neutrophils in vitro. Moreover, we found that the adenosine 2A receptor (A2AR), a known anti-inflammatory G protein-coupled receptor (GPCR), could inhibit LPS-induced neutrophil apoptosis by suppressing the LPS-induced autophagy. Activation of A2AR suppressed LPS-induced autophagy by inhibiting the ROS-JNK pathway as well as promoting GPCR βϒ subunit–AKT signaling. The A2AR-inhibited autophagy suppressed apoptosis of neutrophils by blocking caspase8, caspase3 and PARP signaling. These findings not only increase our understandings of neutrophils’ fate and function in response to systemic inflammation, but also identify a novel anti-inflammatory role of A2AR in modulating neutrophils’ survival during inflammation. PMID:27647162

  9. Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer-related cachexia-anorexia syndrome (CAS) and non-malignant CAS of the alimentary tract.

    PubMed

    Diakowska, Dorota; Krzystek-Korpacka, Malgorzata; Markocka-Maczka, Krystyna; Diakowski, Witold; Matusiewicz, Malgorzata; Grabowski, Krzysztof

    2010-08-01

    We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non-malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract.

  10. Protective role of surface Toll-like receptor 9 expressing neutrophils in local inflammation during systemic inflammatory response syndrome in mice.

    PubMed

    Meng, Xiuping; Sun, Wei; Ren, Yunjia; Xiao, Yue; Zhao, Peiyan; Lu, Wenting; Hua, Li; Wang, Luowei; Wang, Liying; Yu, Yongli

    2017-10-01

    Clinically, systemic inflammatory response syndrome (SIRS) occurs after serious trauma or sepsis. In sepsis, neutrophils are the major effector cells responsible for eliminating pathogens. However, the role of neutrophils in development of SIRS, especially in local inflammatory area, is controversial. In this study, we established a SIRS mouse model characterized with cytokine-mediated lethal shock by intraperitoneal injection of oligodexynucleotides containing CpG motifs (CpG ODN) in D-galactosamine (D-GalN) sensitized mice based on our previous work and found that abundant neutrophils were rapidly recruited into the peritoneal cavity, where some neutrophils expressed surface TLR9 (sTLR9), defined as sTLR9(+) neutrophils. Along with the progression of SIRS, the expression of sTLR9 in sTLR9(+) neutrophils isolated from peritoneal lavage cells (PLCs) was declined in accompany with an increase in the level of the inflammatory cytokine TNFα and a decrease in the level of the anti-inflammatory cytokine IL-10 in Ly6G(+) PLCs. When using CCT ODN, an oligodeoxynucleotide with CCT repeats, which we have previously shown to be capable of rescuing mice from lethal shock, the expression of sTLR9 on neutrophils was significantly elevated. Adoptive therapy using early recruited neutrophil-rich PLCs containing sTLR9(+) neutrophils that express high levels of sTLR9, could rescue mice from SIRS. Overall, the data reveal that the early recruited sTLR9(+) neutrophils may, at least in the area of local inflammation, play a protective role during SIRS development and provide a method to rescue the patients with severe SIRS via the up-regulation of sTLR9 levels on the surface of neutrophils or via adoptive therapy with protective sub-populations of neutrophils. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. HIV-1 tuberculosis-associated immune reconstitution inflammatory syndrome.

    PubMed

    Lai, Rachel P J; Meintjes, Graeme; Wilkinson, Robert J

    2016-03-01

    Patients co-infected with HIV-1 and tuberculosis (TB) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) following commencement of antiretroviral therapy (ART). TB-IRIS is characterized by transient but severe localized or systemic inflammatory reactions against Mycobacterium tuberculosis antigens. Here, we review the risk factors and clinical management of TB-IRIS, as well as the roles played by different aspects of the immune response in contributing to TB-IRIS pathogenesis.

  12. Investigating the Impact of Different Suspicion of Infection Criteria on the Accuracy of Quick Sepsis-Related Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and Early Warning Scores.

    PubMed

    Churpek, Matthew M; Snyder, Ashley; Sokol, Sarah; Pettit, Natasha N; Edelson, Dana P

    2017-07-21

    Studies in sepsis are limited by heterogeneity regarding what constitutes suspicion of infection. We sought to compare potential suspicion criteria using antibiotic and culture order combinations in terms of patient characteristics and outcomes. We further sought to determine the impact of differing criteria on the accuracy of sepsis screening tools and early warning scores. Observational cohort study. Academic center from November 2008 to January 2016. Hospitalized patients outside the ICU. None. Six criteria were investigated: 1) any culture, 2) blood culture, 3) any culture plus IV antibiotics, 4) blood culture plus IV antibiotics, 5) any culture plus IV antibiotics for at least 4 of 7 days, and 6) blood culture plus IV antibiotics for at least 4 of 7 days. Accuracy of the quick Sepsis-related Organ Failure Assessment score, Sepsis-related Organ Failure Assessment score, systemic inflammatory response syndrome criteria, the National and Modified Early Warning Score, and the electronic Cardiac Arrest Risk Triage score were calculated for predicting ICU transfer or death within 48 hours of meeting suspicion criteria. A total of 53,849 patients met at least one infection criteria. Mortality increased from 3% for group 1 to 9% for group 6 and percentage meeting Angus sepsis criteria increased from 20% to 40%. Across all criteria, score discrimination was lowest for systemic inflammatory response syndrome (median area under the receiver operating characteristic curve, 0.60) and Sepsis-related Organ Failure Assessment score (median area under the receiver operating characteristic curve, 0.62), intermediate for quick Sepsis-related Organ Failure Assessment (median area under the receiver operating characteristic curve, 0.65) and Modified Early Warning Score (median area under the receiver operating characteristic curve 0.67), and highest for National Early Warning Score (median area under the receiver operating characteristic curve 0.71) and electronic Cardiac Arrest

  13. Auto-inflammatory fever syndromes.

    PubMed

    Padeh, Shai; Berkun, Yakov

    2007-08-01

    Human autoinflammatory diseases (except for PFAPA) are a heterogeneous group of genetically determined diseases characterized by seemingly unprovoked inflammation in the absence of autoimmune or infective causes (Table 2). The last decade has witnessed tremendous advances in the understanding of these disorders. These advances have allowed therapeutic interventions resulting in improvement in the short-term and long-term morbidity of all of these diseases. Future research into the molecular mechanisms underlying these inflammatory diseases should lead to a better understanding of inflammatory diseases in general and, it is hoped, to better and more targeted therapies.

  14. Lactobacillus casei DG and its postbiotic reduce the inflammatory mucosal response: an ex-vivo organ culture model of post-infectious irritable bowel syndrome.

    PubMed

    Compare, Debora; Rocco, Alba; Coccoli, Pietro; Angrisani, Debora; Sgamato, Costantino; Iovine, Barbara; Salvatore, Umberto; Nardone, Gerardo

    2017-04-14

    The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model. Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting. At baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment. LC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D.

  15. Auto inflammatory syndromes: Diagnosis and treatment.

    PubMed

    Stankovic, Katia; Grateau, Gilles

    2007-12-01

    Hereditary recurrent fevers are rare genetic diseases characterized by apparently spontaneous attacks of inflammation. They include familial Mediterranean fever (FMF); tumor necrosis factor (TNF) receptor periodic syndrome (TRAPS); hyperimmunoglobulinemia D syndrome (HIDS); and hereditary periodic fevers related to mutations in the CIAS1 (cold induced autoinflammatory syndrome 1) gene, such as Muckle-Wells syndrome, familial cold urticaria, and CINCA/NOMID (chronic infantile neurological cutaneous and articular/neonatal-onset multisystemic inflammatory disease). Musculoskeletal manifestations are common. They may occur as features of the acute inflammatory attacks or persist for longer periods. Among them, the most common include arthritis of the large and medium-sized joints in FMF and CINCA, arthralgia in HIDS, and myalgia or pseudo-fasciitis in TRAPS. The outcome is usually favorable, although joint destruction may develop in CINCA or at the hip in FMF. The recurrent bouts of fever and accompanying clinical manifestations suggest the diagnosis, which can be confirmed by genetic testing. Among differential diagnoses, infection should be considered routinely. The treatment of the inflammatory attacks is nonspecific. New pathophysiological insights have led to the development of promising maintenance treatments designed to reduce the number and severity of the inflammatory attacks and to diminish the risk of secondary amyloidosis.

  16. Treatment and prevention of inflammatory responses and oxidative stress in patients with obstructive sleep apnea hypopnea syndrome using Chinese herbal medicines

    PubMed Central

    Chen, Qin; Lin, Rong Jing; Hong, Xuchu; Ye, Lin; Lin, Qichang

    2016-01-01

    The present study aimed to investigate the therapeutic effects of Chinese herbal medicines for the treatment and prevention of inflammatory responses and oxidative stress in obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 60 patients with OSAHS were randomly divided into two groups (n=30/group): The experimental group, who received the conventional treatment + oral administration of the traditional Chinese herbal formula, Jiawei Di Tan Tang; and the control group, who received the conventional treatment only. OSAHS patients were included in the current study if they presented with snoring and had an apnea-hypopnea index (AHI) of >30 in a polysomnography study, without comorbidities. The therapeutic course lasted 12 weeks in both groups. Alterations to the mean clinical symptom score, Epworth sleepiness scale (ESS) and AHI scores, lowest nocturnal blood oxygen saturation (SaO2) and the serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and C-reactive protein (CRP) prior to and following treatment were observed. The mean clinical symptom score was significantly decreased in the experimental group post-treatment compared with the control group (P<0.05). In addition, the clinical symptoms in the experimental group were significantly improved following treatment compared with pre-treatment symptoms (P<0.05). Furthermore, the ESS and AHI scores, lowest nocturnal SaO2 and serum levels of SOD, MDA, IL-6, TNF-α and CRP were significantly improved in the experimental group post-treatment compared with the control group (P<0.05). These parameters in the experimental group were also significantly improved post-treatment compared with those pre-treatment (P<0.05). The results of the present study suggested that oral administration of the traditional Chinese herbal formula Jiawei Di Tan Tang was able to attenuate oxidative stress and inflammatory responses in patients with OSAHS, and thus may

  17. Effects of insulin combined with ethyl pyruvate on inflammatory response and oxidative stress in multiple-organ dysfunction syndrome rats with severe burns.

    PubMed

    Wang, Zhanke; Chen, Rongjian; Zhu, Zhongzhen; Zhang, Xiaoyun; Wang, Shiliang

    2016-11-01

    Inflammation response and oxidative stress promote the occurrence and development of multiple-organ dysfunction syndrome (MODS). Eighty MODS rats with third-degree burns were divided randomly into 4 groups: insulin, ethyl pyruvate (EP), insulin combined with EP, and control. Blood levels of glucose, alanine aminotransferase (ALT), creatine (CRE), creatine kinase (CK), tumor necrosis factor α (TNF-α), high-mobility group box 1 (HMGB-1), malondialdehyde (MDA), and total antioxidant capacity (TAC) before as well as 1, 3, 5, and 7 days after burns were measured. Blood levels of ALT, CRE, CK, TNF-α, HMGB-1, and MDA in INS, EP, and INS+EP groups at different time points were significantly lower, and TAC was significantly higher than that in the control group (C) (P<.01). These parameters in the INS+EP group were significantly lower, and TAC was significantly higher than that in INS and EP groups (P<.01). Blood levels of TNF-α, HMGB-1, and TAC in the INS group at different time points after burns were significantly lower, and MDA was significantly higher than that in the EP group (P<.01). Insulin combined with EP can effectively reduce the inflammatory response, oxidative stress, and main organ dysfunctions in MODS rats after severe burns. The therapeutic effect of insulin combined with EP is superior to single-agent treatment. The insulin anti-inflammatory effect is better than that of pyruvic acid ethyl ester, and the ethyl pyruvate antioxidation effect is better than that of insulin. The insulin can treat inflammation, whereas EP can reduce oxidative stress in MODS rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Subclinical Inflammatory Status in Rett Syndrome

    PubMed Central

    Cortelazzo, Alessio; De Felice, Claudio; Guerranti, Roberto; Landi, Claudia; Valacchi, Giuseppe; Ciccoli, Lucia; Hayek, Joussef

    2014-01-01

    Inflammation has been advocated as a possible common central mechanism for developmental cognitive impairment. Rett syndrome (RTT) is a devastating neurodevelopmental disorder, mainly caused by de novo loss-of-function mutations in the gene encoding MeCP2. Here, we investigated plasma acute phase response (APR) in stage II (i.e., “pseudo-autistic”) RTT patients by routine haematology/clinical chemistry and proteomic 2-DE/MALDI-TOF analyses as a function of four major MECP2 gene mutation types (R306C, T158M, R168X, and large deletions). Elevated erythrocyte sedimentation rate values (median 33.0 mm/h versus 8.0 mm/h, P < 0.0001) were detectable in RTT, whereas C-reactive protein levels were unchanged (P = 0.63). The 2-DE analysis identified significant changes for a total of 17 proteins, the majority of which were categorized as APR proteins, either positive (n = 6 spots) or negative (n = 9 spots), and to a lesser extent as proteins involved in the immune system (n = 2 spots), with some proteins having overlapping functions on metabolism (n = 7 spots). The number of protein changes was proportional to the severity of the mutation. Our findings reveal for the first time the presence of a subclinical chronic inflammatory status related to the “pseudo-autistic” phase of RTT, which is related to the severity carried by the MECP2 gene mutation. PMID:24511209

  19. Subclinical inflammatory status in Rett syndrome.

    PubMed

    Cortelazzo, Alessio; De Felice, Claudio; Guerranti, Roberto; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Zollo, Gloria; Landi, Claudia; Valacchi, Giuseppe; Ciccoli, Lucia; Bini, Luca; Hayek, Joussef

    2014-01-01

    Inflammation has been advocated as a possible common central mechanism for developmental cognitive impairment. Rett syndrome (RTT) is a devastating neurodevelopmental disorder, mainly caused by de novo loss-of-function mutations in the gene encoding MeCP2. Here, we investigated plasma acute phase response (APR) in stage II (i.e., "pseudo-autistic") RTT patients by routine haematology/clinical chemistry and proteomic 2-DE/MALDI-TOF analyses as a function of four major MECP2 gene mutation types (R306C, T158M, R168X, and large deletions). Elevated erythrocyte sedimentation rate values (median 33.0 mm/h versus 8.0 mm/h, P < 0.0001) were detectable in RTT, whereas C-reactive protein levels were unchanged (P = 0.63). The 2-DE analysis identified significant changes for a total of 17 proteins, the majority of which were categorized as APR proteins, either positive (n = 6 spots) or negative (n = 9 spots), and to a lesser extent as proteins involved in the immune system (n = 2 spots), with some proteins having overlapping functions on metabolism (n = 7 spots). The number of protein changes was proportional to the severity of the mutation. Our findings reveal for the first time the presence of a subclinical chronic inflammatory status related to the "pseudo-autistic" phase of RTT, which is related to the severity carried by the MECP2 gene mutation.

  20. Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

    PubMed Central

    Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Lepoutre, Veronique; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Rao, Sowmya R.; Macklin, Eric A.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.; Korzenik, Joshua; Denninger, John W.

    2015-01-01

    Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that

  1. Inflammatory Response in Islet Transplantation

    PubMed Central

    Kanak, Mazhar A.; Kunnathodi, Faisal; Lawrence, Michael C.; Levy, Marlon F.

    2014-01-01

    Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation. PMID:24883060

  2. Paradoxical Mycobacterium tuberculosis meningitis immune reconstitution inflammatory syndrome in an HIV-infected child.

    PubMed

    Kalk, Emma; Technau, Karl; Hendson, Willy; Coovadia, Ashraf

    2013-02-01

    Immune reconstitution inflammatory syndrome occurs in a subset of HIV-infected individuals as the immune system recovers secondary to antiretroviral therapy. An exaggerated and uncontrolled inflammatory response to antigens of viable or nonviable organisms is characteristic, with clinical deterioration despite improvement in laboratory indicators. We describe a fatal case of Mycobacterium tuberculosis meningitis immune reconstitution inflammatory syndrome in an HIV-infected child and review the literature.

  3. Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: a prospective, observational, cohort study.

    PubMed

    Anand, Dimple; Das, Sabari; Bhargava, Seema; Srivastava, Lalit Mohan; Garg, Ashish; Tyagi, Niraj; Taneja, Saurabh; Ray, Sumit

    2015-02-01

    Differentiation between culture-negative sepsis and noninfectious systemic inflammatory response syndrome (SIRS) remains a diagnostic challenge for clinicians, both conditions having similar clinical presentations. Therefore, a swift accurate diagnostic tool, which helps differentiate these 2 conditions would immensely aid appropriate therapeutic continuum. This prospective study was conducted to evaluate the potential diagnostic role of biomarkers, procalcitonin (PCT) and interleukin 6 (IL-6), in culture-negative sepsis patients. Enrolled patients (208) included 46 noninfectious SIRS, 90 culture-negative sepsis, and 72 culture-positive sepsis. Culture, PCT, and IL-6 estimations were performed on day 1 of intensive care unit admission. Procalcitonin and IL-6 levels were significantly higher (P < .001) in both culture-negative and culture-positive groups as compared with SIRS group. Procalcitonin was a better predictor of sepsis in both culture-negative (area under curves 0.892 vs 0.636) and culture-positive (area under curves 0.959 vs 0.784) groups as compared with IL-6. In culture-negative group, the best cutoff point for PCT was at 1.43 ng/mL (92% sensitivity; 83% negative predictive value), best cutoff point for IL-6 was at 219.85 pg/mL (47% sensitivity and 42% negative predictive value). Procalcitonin can accurately differentiate culture-negative sepsis from noninfectious SIRS and thereby contribute to early diagnosis and effective management of these conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Serum levels of procalcitonin as a biomarker for differentiating between sepsis and systemic inflammatory response syndrome in the neurological intensive care unit.

    PubMed

    Tian, Ge; Pan, Su-yue; Ma, Gang; Liao, Wei; Su, Quan-guan; Gu, Bao-chun; Qin, Kun

    2014-07-01

    We explored the value of procalcitonin (PCT) to differentiate sepsis from systemic inflammatory response syndrome (SIRS), and determine sepsis severity in the neurological intensive care unit (NICU). Blood samples were measured for C-reactive protein (CRP) and PCT levels upon NICU admission, on the day of diagnosis of SIRS or sepsis, and at 3 and 7 days after diagnosis. We found that there were significant differences in serum levels of CRP and PCT as well as Glasgow Coma Scale (GCS) score upon admission between the SIRS and sepsis groups (p<0.05). CRP and white blood cell levels were not significantly different when attempting to differentiate sepsis severity (p>0.05). Multiple comparisons showed that significant differences in serum PCT levels were observed between sepsis and severe sepsis groups, as well as sepsis and septic shock groups (p<0.05). We obtained the highest sensitivity and specificity for SIRS and sepsis with cut-off values of 2 ng/mL for PCT, 44 mg/dL for CRP, and 4 for the GCS. There were no differences in CRP and PCT levels between cerebrovascular disease and non-cerebrovascular disease groups (p>0.05). No differences were found between viral and bacterial meningitis groups (p>0.05). PCT levels are valuable in discriminating sepsis from SIRS and determining sepsis severity in critically ill patients with neurological disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Interleukin-6 and C-reactive protein are overexpressed in the liver of perinatal deaths diagnosed with fetal inflammatory response syndrome.

    PubMed

    Pereira, Lívia Helena M; Machado, Juliana R; Olegário, Janaínna G P; Rocha, Laura P; Silva, Marcos V; Guimarães, Camila S O; Reis, Marlene A; Castellano, Lúcio Roberto; Ramalho, Fernando S; Corrêa, Rosana R M

    2014-01-01

    Anatomopathologic studies have failed to define the fetal inflammatory response syndrome (FIRS) as a cause of fetal death. Here, liver fragments of perinatal autopsies were collected at a university hospital from 1990 to 2009 and classified according to the cause of death, perinatal stress, and gestational age (GA) of the fetus. IL-6, TNF-α, and C-reactive protein (CRP) expression were immunostained, respectively, with primary antibody. Cases with congenital malformation, ascending infection, and perinatal anoxia showed increased IL-6, CRP, and TNF-α, respectively. Prematures presented higher expression of IL-6 whereas term births showed higher expression of CRP. Cases classified as acute stress presented higher expression of IL-6 and TNF-α and cases with chronic stress presented higher expression of CRP. GA correlated negatively with IL-6 and positively with CRP and TNF-α. Body weight correlated negatively with IL-6 and positively with CRP and TNF-α. Despite the diagnosis of FIRS being clinical and based on serum parameters, the findings in the current study allow the inference of FIRS diagnosis in the autopsied infants, based on an in situ liver analysis of these markers.

  6. Use of n-3 PUFAs can decrease the mortality in patients with systemic inflammatory response syndrome: a systematic review and meta-analysis.

    PubMed

    Wan, Xiao; Gao, Xuejin; Bi, Jingcheng; Tian, Feng; Wang, Xinying

    2015-03-31

    There have been several meta-analyses evaluating the effect of n-3 polyunsaturated fatty acids (PUFAs) in critically ill patients, but of these, none focused on patients with systemic inflammatory response syndrome (SIRS). The objective of this meta-analysis was to evaluate the effect of omega-3 fatty acids (n-3 FAs) on this narrow subset. All relevant articles were searched on MEDLINE, EMBASE, SpringerLink, and the Cochrane Database of Systematic Reviews from 1990 to 2014. Meta-analyses were used to evaluate risk ratios and mean differences with 95% confidence intervals between the n-3 PUFA group and the control group. Subgroup analyses were conducted in terms of the route of fish oil. Nine randomized controlled trials (RCTs) with 783 adult patients were included in this study. Compared with control groups, n-3 FA provision can significantly reduce the incidence of mortality (RR: 0.77 [0.60, 0.97]; P=0.03; I2=0%). Secondary outcomes showed no significant differences between groups except for shorter length of hospital stay (weighted mean difference: -10.56 [-19.76, -1.36], p<0.00001, I2=99%). Overall, this meta-analysis from RCTs indicates that provision of n-3 PUFAs has a therapeutic effect on survival rate in patients with SIRS.

  7. Branched DNA-based Alu quantitative assay for cell-free plasma DNA levels in patients with sepsis or systemic inflammatory response syndrome.

    PubMed

    Hou, Yan-Qiang; Liang, Dong-Yu; Lou, Xiao-Li; Zhang, Mei; Zhang, Zhen-huan; Zhang, Lu-rong

    2016-02-01

    Cell-free circulating DNA (cf-DNA) can be detected by various of laboratory techniques. We described a branched DNA-based Alu assay for measuring cf-DNA in septic patients. Compared to healthy controls and systemic inflammatory response syndrome (SIRS) patients, serum cf-DNA levels were significantly higher in septic patients (1426.54 ± 863.79 vs 692.02 ± 703.06 and 69.66 ± 24.66 ng/mL). The areas under the receiver operating characteristic curve of cf-DNA for normal vs sepsis and SIRS vs sepsis were 0.955 (0.884-1.025), and 0.856 (0.749-0.929), respectively. There was a positive correlation between cf-DNA and interleukin 6 or procalcitonin or Acute Physiology and Chronic Health Evaluation II. The cf-DNA concentration was higher in intensive care unit nonsurviving patients compared to surviving patients (2183.33 ± 615.26 vs 972.46 ± 648.36 ng/mL; P < .05). Branched DNA-based Alu assays are feasible and useful to quantify serum cf-DNA levels. Increased cf-DNA levels in septic patients might complement C-reactive protein and procalcitonin in a multiple marker format. Cell-free circulating DNA might be a new marker in discrimination of sepsis and SIRS. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. B-1 cells temper endotoxemic inflammatory responses.

    PubMed

    Barbeiro, Denise Frediani; Barbeiro, Hermes Vieira; Faintuch, Joel; Ariga, Suely K Kubo; Mariano, Mario; Popi, Ana Flávia; de Souza, Heraldo Possolo; Velasco, Irineu Tadeu; Soriano, Francisco Garcia

    2011-03-01

    Sepsis syndrome is caused by inappropriate immune activation due to bacteria and bacterial components released during infection. This syndrome is the leading cause of death in intensive care units. Specialized B-lymphocytes located in the peritoneal and pleural cavities are known as B-1 cells. These cells produce IgM and IL-10, both of which are potent regulators of cell-mediated immunity. It has been suggested that B-1 cells modulate the systemic inflammatory response in sepsis. In this study, we conducted in vitro and in vivo experiments in order to investigate a putative role of B-1 cells in a murine model of LPS-induced sepsis. Macrophages and B-1 cells were studied in monocultures and in co-cultures. The B-1 cells produced the anti-inflammatory cytokine IL-10 in response to LPS. In the B-1 cell-macrophage co-cultures, production of proinflammatory mediators (TNF-α, IL-6 and nitrite) was lower than in the macrophage monocultures, whereas that of IL-10 was higher in the co-cultures. Co-culture of B-1 IL-10(-/-) cells and macrophages did not reduce the production of the proinflammatory mediators (TNF-α, IL-6 and nitrite). After LPS injection, the mortality rate was higher among Balb/Xid mice, which are B-1 cell deficient, than among wild-type mice (65.0% vs. 0.0%). The Balb/Xid mice also presented a proinflammatory profile of TNF-α, IL-6 and nitrite, as well as lower levels of IL-10. In the early phase of LPS stimulation, B-1 cells modulate the macrophage inflammatory response, and the main molecular pathway of that modulation is based on IL-10-mediated intracellular signaling.

  9. Obesity-Driven Gut Microbiota Inflammatory Pathways to Metabolic Syndrome

    PubMed Central

    Cavalcante-Silva, Luiz H. A.; Galvão, José G. F. M.; da Silva, Juliane Santos de França; de Sales-Neto, José M.; Rodrigues-Mascarenhas, Sandra

    2015-01-01

    The intimate interplay between immune system, metabolism, and gut microbiota plays an important role in controlling metabolic homeostasis and possible obesity development. Obesity involves impairment of immune response affecting both innate and adaptive immunity. The main factors involved in the relationship of obesity with inflammation have not been completely elucidated. On the other hand, gut microbiota, via innate immune receptors, has emerged as one of the key factors regulating events triggering acute inflammation associated with obesity and metabolic syndrome. Inflammatory disorders lead to several signaling transduction pathways activation, inflammatory cytokine, chemokine production and cell migration, which in turn cause metabolic dysfunction. Inflamed adipose tissue, with increased macrophages infiltration, is associated with impaired preadipocyte development and differentiation to mature adipose cells, leading to ectopic lipid accumulation and insulin resistance. This review focuses on the relationship between obesity and inflammation, which is essential to understand the pathological mechanisms governing metabolic syndrome. PMID:26635627

  10. Inflammatory Responses in Brain Ischemia

    PubMed Central

    Kawabori, Masahito; Yenari, Midori A.

    2017-01-01

    Brain infarction causes tissue death by ischemia due to occlusion of the cerebral vessels and recent work has shown that post stroke inflammation contributes significantly to the development of ischemic pathology. Because secondary damage by brain inflammation may have a longer therapeutic time window compared to the rescue of primary damage following arterial occlusion, controlling inflammation would be an obvious therapeutic target. A substantial amount of experimentall progress in this area has been made in recent years. However, it is difficult to elucidate the precise mechanisms of the inflammatory responses following ischemic stroke because inflammation is a complex series of interactions between inflammatory cells and molecules, all of which could be either detrimental or beneficial. We review recent advances in neuroinflammation and the modulation of inflammatory signaling pathways in brain ischemia. Potential targets for treatment of ischemic stroke will also be covered. The roles of the immune system and brain damage versus repair will help to clarify how immune modulation may treat stroke. PMID:25666795

  11. OTULIN deficiency causes auto-inflammatory syndrome.

    PubMed

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2016-11-01

    Ubiquitin chains assembled via the N-terminal methionine (Met1 or linear ubiquitin), conjugated by the linear ubiquitin chain assembly complex (LUBAC), participate in NF-κΒ-dependent inflammatory signaling and immune responses. A recent report in Cell finds that OTULIN, a deubiquitinase that selectively cleaves Met1-linked ubiquitin chains, is essential for restraining inflammation in vivo.

  12. Can mean platelet volume and mean platelet volume/platelet count ratio be used as a diagnostic marker for sepsis and systemic inflammatory response syndrome?

    PubMed Central

    Ates, Selma; Oksuz, Hafıze; Dogu, Bırsen; Bozkus, Fulsen; Ucmak, Hasan; Yanıt, Fadime

    2015-01-01

    Objectives: To determine whether the mean platelet volume (MPV) and MPV/platelet (PLT) values can be used in the study of sepsis and systemic inflammatory response syndrome (SIRS). Methods: In this retrospective case-controlled study, 69 sepsis, 69 SIRS patients, and 72 control group who were treated in the years 2012-2013 were reviewed, and both the MPV and MPV/PLT rates were evaluated in all groups at Kahramanmaras Sutcu Imam University Intensive Care Unit, Kahramanmaras, Turkey. Results: Statistically significant difference was found between sepsis, SIRS, and control groups when comparing the MPV and MPV/PLT ratio (p<0.05), and no significant difference was found between sepsis and SIRS groups in terms of MPV and MPV/PLT ratio (p>0.05). Mean platelet volume values for sepsis and control groups was 10.07/8.731 femtoliter (fL) (p=0.000), and 9.45/8.731 fL (p=0.000) for SIRS and control groups. In the group of sepsis patients, the MPV was found to be at cut-off 8.915, sensitivity 71%, and specificity 63.9%. In the group of patients with SIRS, MPV was found to be at cut-off 8.85, sensitivity 69.6%, and specificity 62.5%. For the MPV/PLT values, the specificity and sensitivity were found to be insignificant. Conclusion: This study shows that although there was no significant reduction in the PLT values between the sepsis and SIRS patients, the MPV and MPV/PLT ratio values were found to have significant differences. However, the specificity and sensitivity of the values were not reliable standard to be used as a test. PMID:26446329

  13. Can mean platelet volume and mean platelet volume/platelet count ratio be used as a diagnostic marker for sepsis and systemic inflammatory response syndrome?

    PubMed

    Ates, Selma; Oksuz, Hafıze; Dogu, Bırsen; Bozkus, Fulsen; Ucmak, Hasan; Yanıt, Fadıme

    2015-10-01

    To determine whether the mean platelet volume (MPV) and MPV/platelet (PLT) values can be used in the study of sepsis and systemic inflammatory response syndrome (SIRS). In this retrospective case-controlled study, 69 sepsis, 69 SIRS patients, and 72 control group who were treated in the years 2012-2013 were reviewed, and both the MPV and MPV/PLT rates were evaluated in all groups. Statistically significant difference was found between sepsis, SIRS, and control groups when comparing the MPV and MPV/PLT ratio (p less than 0.05), and no significant difference was found between sepsis and SIRS groups in terms of MPV and MPV/PLT ratio (p more than 0.05). Mean platelet volume values for sepsis and control groups was 10.07/8.731 femtoliter (fL) (p=0.000), and 9.45/8.731 fL (p=0.000) for SIRS and control groups. In the group of sepsis patients, the MPV was found to be at cut-off 8.915, sensitivity 71%, and specificity 63.9%. In the group of patients with SIRS, MPV was found to be at cut-off 8.85, sensitivity 69.6%, and specificity 62.5%. For the MPV/PLT values, the specificity and sensitivity were found to be insignificant. This study shows that although there was no significant reduction in the PLT values between the sepsis and SIRS patients, the MPV and MPV/PLT ratio values were found to have significant differences. However, the specificity and sensitivity of the values were not reliable standard to be used as a test.

  14. Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects.

    PubMed

    Wang, Huijuan; Zhang, Pengjun; Chen, Weijun; Feng, Dan; Jia, Yanhong; Xie, Li-xin

    2012-02-11

    Serum microRNAs may be useful biomarkers for diagnosing human diseases. We investigated serum levels of miR-15a and miR-16 in patients with sepsis and systemic inflammatory response syndrome (SIRS) without infection. We enrolled 166 sepsis patients, 32 SIRS patients, and 24 normal controls. Serum miR-15a and miR-16 expression levels were determined by quantitative reverse transcriptase polymerase chain reaction assays (qRT-PCR). Serum miR-15a (p<0.001) and miR-16 (p<0.05) were both significantly higher in sepsis patients compared with normal controls, and miR-15a (p<0.001) and miR-16 (p<0.01) levels in SIRS patients were also significantly higher than those in normal controls. Serum miR-15a and miR-16 levels were not correlated with white blood cell counts. Receiver operating characteristic curves showed that miR-15a had the highest area under the curve of 0.858 [95% confidence interval (CI) 0.800-0.916] for the diagnosis of sepsis compared with C reactive protein and procalcitonin with areas under the curve of 0.572 (95% CI 0.479-0.665; p=0.198) and 0.605 (95% CI 0.443-0.767; p=0.168), respectively. When its cut-off point was set at 0.21, serum miR-15a had a sensitivity of 68.3% and a specificity of 94.4%. Serum miR-15a and miR-16 can both distinguish sepsis/SIRS from normal controls. miR-15a may be a biomarker that distinguishes between sepsis and SIRS.

  15. [Use of fish oil lipid emulsion in patients undergoing major surgery and those with systemic inflammatory response syndrome: a cost-effectiveness analysis].

    PubMed

    Gao, Jian; Ji, Chun-yan; Wu, Guo-hao

    2012-05-01

    To investigate the cost-effectiveness of fish oil in patients undergoing major surgery and those with systemic inflammatory response syndrome(SIRS). A retrospective study was conducted in patients undergoing major surgery and those with SIRS on admission in the Zhongshan Hospital from January 2008 to December 2011. Fish oil group was enrolled and matched to control group by 1:2 for gender, age, diagnosis, and surgical procedure. There were 220 pairs of patients who were not admitted to ICU, 102 pairs of patients admitted to ICU, and 66 pairs of patients with SIRS. The clinical outcomes and costs were measured and cost-effectiveness analyses were conducted. The clinical outcomes and costs showed no significant difference between the fish oil group and the control group in those patients who were not admitted to ICU(P>0.05). Fish oil fat emulsion supplementation significantly reduced the length of total hospital stay, postoperative hospital stay, ICU stay, re-operation rate, infection rates, perioperative mortality in patients admitted to ICU and those with SIRS(P<0.05). The cost-effectiveness ratio of non-reoperation rate, non-infection rate, and survival rate were lower in those patients receiving fish oil fat emulsion as compared with those without fish oil administration. Fish oil fat emulsion supplementation could reduce cost-effectiveness ratios of non-reoperation rate, non-infection rate and survival rate by 105 RMB, 160 RMB, and 89 RMB respectively in major surgical patients who admitted to ICU, and by 670 RMB, 280 RMB, and 220 RMB respectively in SIRS patients. Addition of fish oil fat emulsion to clinical nutrition may have positive effects on critically ill patients. It seems that the effects of fish oil fat are strongly related to the severity of patient's underlying disease. Fish oil fat emulsion supplementation shows acceptable cost-effectiveness ratio and pharmacoeconomic value.

  16. The natural history of the systemic inflammatory response syndrome and the evaluation of SIRS criteria as a predictor of severity in patients hospitalized through emergency services.

    PubMed

    Sun, D; Aikawa, N

    1999-03-01

    Based on the concept of the systemic inflammatory response syndrome (SIRS), a one-year retrospective study was carried out among a total of 2389 patients transported to the emergency room by ambulance. With respect to 351 patients who had all data necessary for evaluating SIRS criteria in 369 hospitalized patients, 200 met SIRS criteria within 24 hours of admission (24h-SIRS). The mortality rate for 24h-SIRS patients was significantly higher than that of non-SIRS patients. The mortality rate for 24h-SIRS patients increased sequentially as more SIRS criteria were met. In 235 patients who met SIRS criteria during hospitalization (overall-SIRS), 108 had sepsis. Of these, 60 developed severe sepsis, and 50 developed septic shock. The mortality rate for patients who had 3 or more consecutive days of SIRS was significantly higher than that for those with less than 3 consecutive SIRS days. Among 153 patients who had all data necessary for APACHEIII scoring within 24 hours of admission, the mortality rate for SIRS patients whose APACHEIII score was 50 or higher was 40.7%, significantly higher than that of other patients. In conclusion, SIRS criteria were demonstrated to be useful as indicators of severity and for predicting outcome in patients hospitalized through emergency services. Patients who met the following criteria were found to be a high-risk population among hospitalized emergency patients with SIRS: (1) Those who had three or more consecutive days of SIRS. (2) Those whose APACHEIII score was 50 or higher.

  17. Prospective evaluation of the acute patient physiologic and laboratory evaluation score and an extended clinicopathological profile in dogs with systemic inflammatory response syndrome.

    PubMed

    Giunti, Massimo; Troia, Roberta; Bergamini, Paolo Famigli; Dondi, Francesco

    2015-01-01

    To investigate the prognostic value of the acute patient physiologic and laboratory evaluation (APPLE) score and relevant clinicopathological markers in dogs with systemic inflammatory response syndrome (SIRS). Prospective observational cohort study. Veterinary teaching hospital. Thirty-three dogs with SIRS admitted to the intensive care unit (ICU) were compared to 35 healthy control dogs. Dogs with SIRS were divided into septic (n = 20) and nonseptic (n = 13) etiologies and as survivors (alive to discharge, n = 22) and nonsurvivors (n = 11: died, n = 6, or humanely euthanized, n = 5). For all dogs, physiological and laboratory parameters were prospectively collected for the calculation of the APPLE fast score. No difference between septic and nonseptic SIRS dogs was detected for any parameter evaluated. Survivors had significantly higher total protein, albumin concentrations, antithrombin activity (ATA), and base excess (BE), as well as significantly lower lactate, urea, creatinine concentrations, urinary protein to creatinine ratio and APPLE fast score compared to nonsurvivors. Higher values of creatinine, lactate, anion gap, alanine transaminase (ALT), and APPLE fast score were significantly associated with an increased risk of death in SIRS dogs, while higher values of total protein, albumin, ATA, and BE were associated with a significantly reduced risk of mortality. When a multivariate binary logistic regression analysis was performed, the APPLE fast score was the only significant parameter retained. The determination of the APPLE fast score in clinical setting, as well as the measurement of APP, ATA, lactate, BE, anion gap, ALT, urinary proteins, and electrolytes may be beneficial for a better assessment of dogs with SIRS. Identified parameters were significantly related with the presence of SIRS and their evaluation should be considered for the assessment of disease severity, and guidance of the decision-making process in critically ill dogs. © Veterinary

  18. Resuscitation with polymeric plasma substitutes is permissive for systemic inflammatory response syndrome and sepsis in multiply injured patients: a retrospective cohort study.

    PubMed

    Sprengel, Kai; Simmen, Hanspeter; Werner, Clément M L; Sulser, Simon; Plecko, Michael; Keller, Catharina; Mica, Ladislav

    2016-10-13

    Multiple trauma is often accompanied by systemic inflammatory response syndrome (SIRS). The aim of this study was to investigate the impact of polymeric plasma substitutes on the development of SIRS or sepsis. We included 2969 patients aged ≥16 years with an Injury Severity Score (ISS) >16 in this study. The sample was subdivided into three groups: patients who did not receive colloids and those who received <5L colloids and >5L colloids within the first 48 h. Data were analyzed using IBM SPSS(®) for Windows version 22.0; analysis of variance was used for continuous normally distributed data and Kruskal-Wallis test for categorical data. The predictive quality of colloid treatment was analyzed using the receiver operating characteristic (ROC) curves. Independent predictively was analyzed by binary logistic regression. Data were considered significant if P < 0.05. Data are presented as the mean ± standard deviation. The SIRS score increased with the amount of colloid used (1.9 ± 1.4 vs. 2.4 ± 1.2 vs. 3.2 ± 0.9; P < 0.001). However, the predictive quality was low, with an area under the ROC of 0.693 for SIRS and 0.669 for sepsis (P < 0.001). Binary logistic regression revealed colloids as an independent factor for the development of SIRS and sepsis (odds ratios: SIRS 3.325 and sepsis 8.984; P < 0.001). Besides other factors, colloids have a significant permissive effect and are independent predictors for the development of SIRS and sepsis in multiply injured patients. Trial registration 'Retrospektive Analysen in der Chirurgischen Intensivmedizin' No. St. V. 01-2008.

  19. An elevated fetal interleukin-6 concentration can be observed in fetuses with anemia due to Rh alloimmunization: implications for the understanding of the fetal inflammatory response syndrome.

    PubMed

    Vaisbuch, Edi; Romero, Roberto; Gomez, Ricardo; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S

    2011-03-01

    The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm prelabor rupture of the membranes and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia. Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. (1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); (2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the fetal IL-6 (r=-0.68, p=0.004); (3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18-2.63 vs. 1.46 pg/ml, IQR 1.76-14.7; p=0.02); (4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization.

  20. Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin.

    PubMed

    Ryan, James C; Wu, Qingzhong; Shoemaker, Ritchie C

    2015-04-02

    Ciguatoxins (CTXs) are polyether marine neurotoxins found in multiple reef-fish species and are potent activators of voltage-gated sodium channels. It is estimated that up to 500,000 people annually experience acute ciguatera poisoning from consuming toxic fish and a small percentage of these victims will develop a chronic, multisymptom, multisystem illness, which can last years, termed a Chronic Inflammatory Response Syndrome (CIRS). Symptoms of ciguatera CIRS include fatigue, cognitive deficits, neurologic deficits, pain and sensitivity to light. There are few treatment options for ciguatera CIRS since little is known about its pathophysiology. This study characterizes the transcriptional profile in whole blood of 11 patients with ciguatera-induced CIRS and 11 normal controls run in duplicate using Agilent one color whole genome microarrays. Differential expression was determined by using a combination of moderated t-test p-value and fold change (FC). Significant genes were subjected to gene ontology, principal component analysis and SVM classification. Seven significant genes found by microarray were validated by PCR. Using a low stringency (p < 0.05 and FC > 1.4) and a high stringency (p < 0.01 and FC > 1.5) filter, the resulting gene sets of 185 and 55, respectively, showed clear separation of cases and controls by PCA as well as 100% classification accuracy by SVM, indicating that the gene profiles can separate patients from controls. PCR results of 7 genes showed a 95% correlation to microarray data. Several genes identified by microarray are important in wound healing (CD9, CD36, vWF and Factor XIII), adaptive immunity (HLA-DQB1, DQB2, IL18R1 and IL5RA) and innate immunity (GZMK, TOLLIP, SIGIRR and VIPR2), overlapping several areas shown to be disrupted in a mouse model of acute exposure to ciguatoxin. Another area of interest was differential expression of long, non-coding sequences, or lncRNA. Disruptions of innate and adaptive immune

  1. An Elevated Fetal IL-6 Concentration Can Be Observed In Fetuses with Anemia Due To Rh Alloimmunization: Implications for the Understanding of the Fetal Inflammatory Response Syndrome

    PubMed Central

    Vaisbuch, Edi; Romero, Roberto; Gomez, Ricardo; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

    2010-01-01

    Objective The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm PROM and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally-defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia. Methods Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/mL. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. Results 1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); 2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration - the lower the hematocrit, the higher the fetal IL-6 (r= −0.68, p=0.004); 3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18–2.63 vs. 1.46 pg/ml, IQR 1.76–14.7; p=0.02); 4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. Conclusions An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization. PMID:20701435

  2. Venipuncture Induced Complex Regional Pain Syndrome Presenting as Inflammatory Arthritis

    PubMed Central

    Arora, Pramod; Mittal, Manoj; Nair, Anugrah; Sultana, Waqia

    2016-01-01

    Venipuncture is one of the most commonly done medical procedures. We report a unique case of a 23-year-old young male who presented with features suggestive of inflammatory arthritis. The symptoms, which initially started on the right side, also involved the other side after a few weeks. Although the patient's symptoms and signs were simulating inflammatory arthritis, he had atypical features like poor response to anti-inflammatory medicines and normal laboratory parameters. His musculoskeletal ultrasonography was also not suggestive of arthritis. His history was reviewed and on direct questioning he revealed a history of venipuncture for blood sample withdrawal, done from right antecubital region for routine health check on the day prior to the onset of symptoms. Complex regional pain syndrome was suspected and triple-phase radioisotope bone scan was done which was highly suggestive of this diagnosis. The patient was managed with multidimensional approach and responded very well to the treatment. Complex regional pain syndrome is usually not thought of in the initial differential diagnosis of inflammatory arthritis. In this report we highlight the need to elicit the often overlooked history of trivial trauma like venipuncture, especially in atypical cases of arthritis. Also the role of newer diagnostic modalities in such cases is emphasized. PMID:27891152

  3. Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome.

    PubMed

    Shahani, Lokesh; Hamill, Richard J

    2016-01-01

    Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement in a previously incompetent human immune system manifesting as worsening of clinical symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory response. IRIS was first recognized in the setting of human immunodeficiency virus, and this clinical setting continues to be where it is most frequently encountered. Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and the underlying pathogen, include excessive activation of the immune system, with increased circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening for opportunistic infections before starting ART is a key element to prevent this phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome and exclusion of alternative diagnoses, particularly underlying infections and drug resistance. Controlled studies supporting the use of pharmacologic interventions in IRIS are scare, and recommendations are based on case series and expert opinions. The only controlled trial published to date, showed reduction in morbidity in patients with paradoxical tuberculosis-related IRIS with the use of oral corticosteroids. There are currently limited data to recommend other anti-inflammatory or immunomodulatory therapies that are discussed in this review, and further research is needed. Ongoing research regarding the immune pathogenesis of IRIS will likely direct future rational therapeutic approaches and clinical trials. Published by Elsevier Inc.

  4. Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs.

    PubMed

    Vlahakos, Demetrios; Arkadopoulos, Nikolaos; Kostopanagiotou, Georgia; Siasiakou, Sofia; Kaklamanis, Loukas; Degiannis, Dimitrios; Demonakou, Maria; Smyrniotis, Vassilios

    2012-04-01

    We have previously shown that deferoxamine (DFO) infusion protected myocardium against reperfusion injury in patients undergoing open heart surgery, and reduced brain edema, intracranial pressure, and lung injury in pigs with acute hepatic ischemia (AHI). The purpose of this research was to study if DFO could attenuate sepsis inflammatory response syndrome (SIRS) and confer renoprotection in the same model of AHI in anesthetized pigs. Fourteen animals were randomly allocated to two groups. In the Group DFO (n=7), 150mg/kg of DFO dissolved in normal saline was continuously infused in animals undergoing hepatic devascularization and portacaval anastomosis. The control group (Group C, n=7) underwent the same surgical procedure and received the same volume of normal saline infusion. Animals were euthanized after 24h. Hematological, biochemical parameters, malondialdehyde (MDA), and cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α) were determined from sera obtained at baseline, at 12h, and after euthanasia. Hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling were used to evaluate necrosis and apoptosis, respectively, in kidney sections obtained after euthanasia. A rapid and substantial elevation (more than 100-fold) of serum IL-6 levels was observed in Group C reaching peak at the end of the experiment, associated with increased production of oxygen free radicals and lipid peroxidation (MDA 3.2±0.1nmol/mL at baseline and 5.5±0.9nmol/mL at the end of the experiment, P<0.05) and various manifestations of SIRS and multiple organ dysfunction (MOD), including elevation of high-sensitivity C-reactive protein, severe hypotension, leukocytosis, thrombocytopenia, hypoproteinemia, and increased serum levels of lactate dehydrogenase (fourfold), alkaline phosphatase (fourfold), alanine aminotransferase (14-fold), and ammonia (sevenfold). In sharp contrast, IL-6 production and lipid

  5. Quick Sepsis-related Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and Early Warning Scores for Detecting Clinical Deterioration in Infected Patients outside the Intensive Care Unit.

    PubMed

    Churpek, Matthew M; Snyder, Ashley; Han, Xuan; Sokol, Sarah; Pettit, Natasha; Howell, Michael D; Edelson, Dana P

    2017-04-01

    The 2016 definitions of sepsis included the quick Sepsis-related Organ Failure Assessment (qSOFA) score to identify high-risk patients outside the intensive care unit (ICU). We sought to compare qSOFA with other commonly used early warning scores. All admitted patients who first met the criteria for suspicion of infection in the emergency department (ED) or hospital wards from November 2008 until January 2016 were included. The qSOFA, Systemic Inflammatory Response Syndrome (SIRS), Modified Early Warning Score (MEWS), and the National Early Warning Score (NEWS) were compared for predicting death and ICU transfer. Of the 30,677 included patients, 1,649 (5.4%) died and 7,385 (24%) experienced the composite outcome (death or ICU transfer). Sixty percent (n = 18,523) first met the suspicion criteria in the ED. Discrimination for in-hospital mortality was highest for NEWS (area under the curve [AUC], 0.77; 95% confidence interval [CI], 0.76-0.79), followed by MEWS (AUC, 0.73; 95% CI, 0.71-0.74), qSOFA (AUC, 0.69; 95% CI, 0.67-0.70), and SIRS (AUC, 0.65; 95% CI, 0.63-0.66) (P < 0.01 for all pairwise comparisons). Using the highest non-ICU score of patients, ≥2 SIRS had a sensitivity of 91% and specificity of 13% for the composite outcome compared with 54% and 67% for qSOFA ≥2, 59% and 70% for MEWS ≥5, and 67% and 66% for NEWS ≥8, respectively. Most patients met ≥2 SIRS criteria 17 hours before the combined outcome compared with 5 hours for ≥2 and 17 hours for ≥1 qSOFA criteria. Commonly used early warning scores are more accurate than the qSOFA score for predicting death and ICU transfer in non-ICU patients. These results suggest that the qSOFA score should not replace general early warning scores when risk-stratifying patients with suspected infection.

  6. Inflammatory peeling skin syndrome caused a novel mutation in CDSN.

    PubMed

    Telem, Dana Fuchs; Israeli, Shirli; Sarig, Ofer; Sprecher, Eli

    2012-04-01

    Generalized peeling skin syndrome (PSS) is a rare autosomal recessive dermatosis manifesting with continuous exfoliation of the stratum corneum. The inflammatory (type B) subtype of PSS was recently found to be caused by deleterious mutations in the CDSN gene encoding corneodesmosin, a major component of desmosomal junctions in the uppermost layers of the epidermis. In the present study, we assessed a 10-month-old baby, who presented with generalized superficial peeling of the skin. Using PCR amplification and direct sequencing, we identified the third PSS-associated mutation in CDSN, a homozygous 4 bp duplication in the second exon of the gene (c.164_167dup GCCT; p.Thr57ProfsX6). These data further support the notion that corneodesmosin deficiency impairs cell-cell adhesion in the upper epidermis, paving the way for an abnormal inflammatory response due to epidermal barrier disruption.

  7. Nutritional modulation of the inflammatory bowel response.

    PubMed

    Ioannidis, Orestis; Varnalidis, Ioannis; Paraskevas, George; Botsios, Dimitrios

    2011-01-01

    Crohn's disease and ulcerative colitis represent distinct phenotypic forms of inflammatory bowel disease and continue to be a common cause of morbidity. The corticosteroids and the immunomodulatory drugs, which are the basis of treatment for the inflammatory bowel diseases, do not assure always satisfactory outcomes. Nutrition has been used in order to modify the inflammatory response of various chronic inflammatory diseases, including Crohn's disease and ulcerative colitis. In the pathogenesis of inflammatory bowel diseases, the intestinal microflora and the intestinal mucosal disorders play a crucial role. Also, the release of reactive oxygen species is a significant factor of initiation and preservation of the inflammatory reaction in these diseases. The advantages of the nutritional treatment derive from the sequestration of intraluminal agents which may promote the inflammatory bowel response or, alternatively, nutrition is able to modify the immune response, reducing the uncontrolled inflammatory reaction. Furthermore, nutrition can enhance the mucosal barrier function and consists a significant source of antioxidants. This review focuses on certain nutritional components that modulate the inflammatory response of the bowel and aims to present a rational thesis regarding the use of nutritional agents in the management of inflammatory bowel diseases.

  8. HIV Immune Recovery Inflammatory Syndrome and Central Nervous System Paracoccidioidomycosis.

    PubMed

    de Almeida, Sérgio Monteiro; Roza, Thiago Henrique

    2017-04-01

    The immune reconstitution inflammatory syndrome (IRIS) is a deregulated inflammatory response to invading microorganisms. It is manifested when there is an abrupt change in host immunity from an anti-inflammatory and immunosuppressive state to a pro-inflammatory state as a result of rapid depletion or removal of factors that promote immune suppression or inhibition of inflammation. The aim of this paper is to discuss and re-interpret the possibility of association of paracoccidioidomycosis (PCM) with IRIS in the central nervous system (CNS) in a case from Brazil published by Silva-Vergara ML. et al. (Mycopathologia 177:137-141, 6). An AIDS patient who was not receiving medical care developed pulmonary PCM successfully treated with itraconazole. The patient developed central nervous system PCM (NPCM) after starting the ARV therapy with recovery of immunity and control of HIV viral load, although it was not interpreted as IRIS by the authors, it fulfills the criteria for CNS IRIS. This could be the first case of NPCM associated with IRIS described. Although not frequent, IRIS must be considered in PCM patients and HIV, from endemic areas or patients that traveled to endemic areas, receiving ARV treatment and with worsening symptoms.

  9. Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Guo, Xiuming; Qin, Xinyue; Zhang, Yuping; Huang, Cheng; Yu, Gang

    2014-04-01

    Polyneuropathy is often an initial manifestation of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome and therefore this disorder is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed electrophysiological data in 20 patients with POEMS syndrome and 36 matched patients with CIDP to compare the electrophysiological features of POEMS syndrome and CIDP. Compared with CIDP controls, POEMS patients demonstrated (1) less prolonged distal motor latency and less reduced motor nerve and sensory nerve conduction velocities, (2) greater reduction of amplitudes of compound motor action potentials (CMAP) in distal stimulation, and similar reduction of amplitudes of CMAP in proximal stimulation, (3) similar reduction of amplitudes of sensory nerve action potentials (SNAP) in median and ulnar nerves, and a greater reduction of amplitudes of SNAP in tibial and peroneal nerves, (4) less temporal dispersion, (5) less frequent conduction block, (6) more frequent neurogenic injury in the muscles of the upper and lower limbs, and more frequent neurogenic injury in the muscles of the lower than upper limbs, (7) similar F wave and H reflex abnormalities, and (8) less frequent skin sympathetic response abnormalities. We concluded that before development of typical clinical manifestations, POEMS neuropathy can be distinguished from CIDP by neural electrophysiological examination. These electrophysiological features can be used for early diagnosis and initiating correct treatment of POEMS syndrome.

  10. Inflammatory lung disease in Rett syndrome.

    PubMed

    De Felice, Claudio; Rossi, Marcello; Leoncini, Silvia; Chisci, Glauco; Signorini, Cinzia; Lonetti, Giuseppina; Vannuccini, Laura; Spina, Donatella; Ginori, Alessandro; Iacona, Ingrid; Cortelazzo, Alessio; Pecorelli, Alessandra; Valacchi, Giuseppe; Ciccoli, Lucia; Pizzorusso, Tommaso; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with "high" (39.8%) and "low" (34.8%) patterns dominating over "mixed" (19.6%) and "simple mismatch" (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease.

  11. [Metabolic syndrome in inflammatory rheumatic diseases].

    PubMed

    Malesci, D; Valentini, G; La Montagna, G

    2006-01-01

    Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.

  12. Inflammatory Lung Disease in Rett Syndrome

    PubMed Central

    De Felice, Claudio; Rossi, Marcello; Chisci, Glauco; Lonetti, Giuseppina; Vannuccini, Laura; Spina, Donatella; Iacona, Ingrid; Cortelazzo, Alessio; Ciccoli, Lucia; Pizzorusso, Tommaso; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with “high” (39.8%) and “low” (34.8%) patterns dominating over “mixed” (19.6%) and “simple mismatch” (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease. PMID:24757286

  13. Compartmentalization of the inflammatory response in sepsis and SIRS.

    PubMed

    Cavaillon, Jean-Marc; Annane, Djillali

    2006-01-01

    Sepsis and systemic inflammatory response syndrome (SIRS) are associated with an exacerbated production of both pro- and anti-inflammatory mediators that are mainly produced within tissues. Although a systemic process, the pathophysiological events differ from organ to organ, and from organ to peripheral blood, leading to the concept of compartmentalization. The nature of the insult (e.g. burn, hemorrhage, trauma, peritonitis), the cellular composition of each compartment (e.g. nature of phagocytes, nature of endothelial cells), and its micro-environment (e.g. local presence of granulocyte-macrophage colony stimulating factor [GM-CSF] in the lungs, low levels of arginine in the liver, release of endotoxin from the gut), and leukocyte recruitment, have a great influence on local inflammation and on tissue injury. High levels of pro-inflammatory mediators (e.g. interleukin-1 [IL-1], tumor necrosis factor [TNF], gamma interferon [IFN-gamma], high mobility group protein-1 [HMGB1], macrophage migration inhibitory factor [MIF]) produced locally and released into the blood stream initiate remote organ injury as a consequence of an organ cross-talk. The inflammatory response within the tissues is greatly influenced by the local delivery of neuromediators by the cholinergic and sympathetic neurons. Acetylcholine and epinephrine contribute with IL-10 and other mediators to the anti-inflammatory compensatory response initiated to dampen the inflammatory process. Unfortunately, this regulatory response leads to an altered immune status of leukocytes that can increase the susceptibility to further infection. Again, the nature of the insult, the nature of the leukocytes, the presence of circulating microbial components, and the nature of the triggering agent employed to trigger cells, greatly influence the immune status of the leukocytes that may differ from one compartment to another. While anti-inflammatory mediators predominate within the blood stream to avoid igniting new

  14. Hansen's disease in association with immune reconstitution inflammatory syndrome.

    PubMed

    George, Anju; Vidyadharan, Suja

    2016-01-01

    Immune reconstitution inflammatory syndrome is characterized by a paradoxical worsening of an existing infection or disease process, soon after initiation of highly active antiretroviral therapy. The first case of leprosy presenting as immune reconstitution inflammatory syndrome was published in 2003. Here we report a case of Hansen's disease borderline tuberculoid presenting with type 1 lepra reaction 5 months after initiation of highly active antiretroviral therapy.

  15. Irritable bowel syndrome, inflammatory bowel disease and the microbiome

    PubMed Central

    Major, Giles; Spiller, Robin

    2014-01-01

    Purpose of review The review aims to update the reader on current developments in our understanding of how the gut microbiota impact on inflammatory bowel disease and the irritable bowel syndrome. It will also consider current efforts to modulate the microbiota for therapeutic effect. Recent findings Gene polymorphisms associated with inflammatory bowel disease increasingly suggest that interaction with the microbiota drives pathogenesis. This may be through modulation of the immune response, mucosal permeability or the products of microbial metabolism. Similar findings in irritable bowel syndrome have reinforced the role of gut-specific factors in this ‘functional’ disorder. Metagenomic analysis has identified alterations in pathways and interactions with the ecosystem of the microbiome that may not be recognized by taxonomic description alone, particularly in carbohydrate metabolism. Treatments targeted at the microbial stimulus with antibiotics, probiotics or prebiotics have all progressed in the past year. Studies on the long-term effects of treatment on the microbiome suggest that dietary intervention may be needed for prolonged efficacy. Summary The microbiome represents ‘the other genome’, and to appreciate its role in health and disease will be as challenging as with our own genome. Intestinal diseases occur at the front line of our interaction with the microbiome and their future treatment will be shaped as we unravel our relationship with it. PMID:24296462

  16. Irritable bowel syndrome, inflammatory bowel disease and the microbiome.

    PubMed

    Major, Giles; Spiller, Robin

    2014-02-01

    The review aims to update the reader on current developments in our understanding of how the gut microbiota impact on inflammatory bowel disease and the irritable bowel syndrome. It will also consider current efforts to modulate the microbiota for therapeutic effect. Gene polymorphisms associated with inflammatory bowel disease increasingly suggest that interaction with the microbiota drives pathogenesis. This may be through modulation of the immune response, mucosal permeability or the products of microbial metabolism. Similar findings in irritable bowel syndrome have reinforced the role of gut-specific factors in this 'functional' disorder. Metagenomic analysis has identified alterations in pathways and interactions with the ecosystem of the microbiome that may not be recognized by taxonomic description alone, particularly in carbohydrate metabolism. Treatments targeted at the microbial stimulus with antibiotics, probiotics or prebiotics have all progressed in the past year. Studies on the long-term effects of treatment on the microbiome suggest that dietary intervention may be needed for prolonged efficacy. The microbiome represents 'the other genome', and to appreciate its role in health and disease will be as challenging as with our own genome. Intestinal diseases occur at the front line of our interaction with the microbiome and their future treatment will be shaped as we unravel our relationship with it.

  17. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity

    PubMed Central

    Watad, Abdulla; David, Paula; Brown, Stav; Shoenfeld, Yehuda

    2017-01-01

    The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto’s thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. PMID:28167927

  18. Metabolic syndrome associated to non-inflammatory Achilles enthesopathy.

    PubMed

    Abate, Michele; Di Carlo, Luigi; Salini, Vincenzo; Schiavone, Cosima

    2014-01-01

    Enthesopathies are frequently found in rheumatic inflammatory diseases, but can be observed also in absence of systemic inflammation. Aging, overuse, and microtraumas can be responsible for enthesis-degenerative phenomena. Despite that Achilles enthesis is the more frequently affected, no systematic study on the risk factors associated to this enthesopathy has been yet performed. The aim of this paper was to assess whether the metabolic syndrome could be associated to entheseal lesions. Forty-five subjects with symptomatic non-inflammatory Achilles enthesopathy were compared to 45 asymptomatic controls. An ultrasound study of the Achilles enthesis was carried out, and the presence/absence of lesions (morphologic abnormalities, calcific deposits, enthesophytes, cortical abnormalities, and adjacent bursitis) was assessed. On the basis of history, comorbidities (osteoarthritis, diabetes, and hypertension) were recorded. In each subject, body mass index (BMI), glucose, total, and HDL cholesterol were also evaluated. All symptomatic subjects showed at ultrasound evaluation at least one structural entheseal alteration; pathologic features in asymptomatic subjects were found in 6/45 (13.3 %) of cases. Higher values of BMI and glucose were found in subjects with symptomatic enthesopathy. At multiple logistic regression analysis, the presence of high values of BMI and glucose was related to a higher probability to detect entheseal lesions. Metabolic syndrome and overweight may have a role in the pathogenesis of Achilles enthesopathy due to their synergistic worsening effect on other pathogenetic factors of tendon degeneration, such age and overuse. Therefore, subjects with metabolic syndrome practicing sports and other activities stressing the Achilles tendon should receive advice for more frequent controls.

  19. Psychological Interventions for Irritable Bowel Syndrome and Inflammatory Bowel Diseases

    PubMed Central

    Ballou, Sarah; Keefer, Laurie

    2017-01-01

    Psychological interventions have been designed and implemented effectively in a wide range of medical conditions, including Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Diseases (IBD). The psychological treatments for IBS and IBD with the strongest evidence base include: cognitive behavioral therapy, hypnosis, and mindfulness-based therapies. The evidence for each of these therapies is reviewed here for both IBS and IBD. In general, there is a stronger and larger evidence base to support the use of psychological interventions in IBS compared with IBD. This is likely due to the high level of psychiatric comorbidity associated with IBS and the involvement of the stress-response in symptom presentation of IBS. Further research in psychosocial interventions for IBD is necessary. Finally, the importance of conceptualizing both IBS and IBD in a biopsychosocial model is discussed and several resources for accessing Clinical Health Psychology materials and referrals are provided. PMID:28102860

  20. Noninvasive assessment of localized inflammatory responses

    PubMed Central

    Zhou, Jun; Tsai, Yi-Ting; Weng, Hong; Tang, Liping

    2011-01-01

    Inflammatory diseases are associated with the accumulation of activated inflammatory cells, particularly polymorphonuclear neutrophils (PMN), which release reactive oxygen species (ROS) to eradicate foreign bodies and microorganisms. To assess the location and extent of localized inflammatory responses, L-012, a highly-sensitive chemiluminescence probe, was employed to non-invasively monitor the production of ROS. We find that L-012-associated chemiluminescence imaging can be used to identify and to quantify the extent of inflammatory responses. Furthermore, regardless of differences among animal models, there is a good linear relationship between chemiluminescence intensity and PMN numbers surrounding inflamed tissue. Depletion of PMN substantially diminished L-012-associated chemiluminescence in vivo. Finally, L-012-associated chemiluminescence imaging was found to be a powerful tool for assessing implant-mediated inflammatory responses by measuring chemiluminescent intensities at the implantation sites. These results support the use of L-012 for monitoring the kinetics of inflammatory responses in vivo via the detection and quantification of ROS production. PMID:22080048

  1. Endothelial Response to Glucocorticoids in Inflammatory Diseases

    PubMed Central

    Zielińska, Karolina A.; Van Moortel, Laura; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

    2016-01-01

    The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients. PMID:28018358

  2. The Pathogenesis of ACLF: The Inflammatory Response and Immune Function.

    PubMed

    Moreau, Richard

    2016-05-01

    Although systemic inflammation is a hallmark of acute-on-chronic liver failure (ACLF), its role in the development of this syndrome is poorly understood. Here the author first summarizes the general principles of the inflammatory response. Inflammation can be triggered by exogenous or endogenous inducers. Important exogenous inducers include bacterial products such as pathogen-associated molecular patterns (PAMPs) and virulence factors. Pathogen-associated molecular patterns elicit inflammation through structural feature recognition (using innate pattern-recognition receptors [PRRs]), whereas virulence factors generally trigger inflammation via functional feature recognition. Endogenous inducers are called danger-associated molecular patterns (DAMPs) and include molecules released by necrotic cells and products of extracellular matrix breakdown. Danger-associated molecular patterns use different PRRs. The purpose of the inflammatory response may differ according to the type of stimulus: The aim of infection-induced inflammation is to decrease pathogen burden, whereas the DAMP-induced inflammation aims to promote tissue repair. An excessive inflammatory response can induce collateral tissue damage (a process called immunopathology). However immunopathology may not be the only mechanism of tissue damage; for example, organ failure can develop because of failed disease tolerance. In this review, the author also discusses how general principles of the inflammatory response can help us to understand the development of ACLF in different contexts: bacterial infection, severe alcoholic hepatitis, and cases in which there is no identifiable trigger.

  3. Plasma interleukin-18 levels are a biomarker of innate immune responses that predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome.

    PubMed

    Tan, Hong Yien; Yong, Yean Kong; Andrade, Bruno B; Shankar, Esaki M; Ponnampalavanar, Sasheela; Omar, Sharifah F S; Narendran, Gopalan; Kamarulzaman, Adeeba; Swaminathan, Soumya; Sereti, Irini; Crowe, Suzanne M; French, Martyn A

    2015-02-20

    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin-18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS. Biomarkers were assayed pre-ART and during TB-IRIS, or equivalent time-point, in a case-control study of Malaysian HIV patients with paradoxical or unmasking TB-IRIS (n = 15), TB no IRIS (n = 14), and no TB or IRIS (n = 15). Findings for interleukin-18 were verified in another cohort of patients with paradoxical TB-IRIS (n = 26) and their controls (n = 22) from India. Interleukin-18 was higher in TB-IRIS patients pre-ART and during the event in both Malaysian patients (P < 0.0001) and Indian patients (P < 0.01). CXCL10 was higher pre-ART (P < 0.001), mainly in paradoxical TB-IRIS patients, and during TB-IRIS (P < 0.001), whereas CXCL8 was only higher during TB-IRIS (P < 0.001). Soluble(s) CD14 was increased in all patients with HIV/TB coinfection pre-ART and during TB-IRIS or equivalent time-point, compared with patients without TB. In contrast, interferon-γ was lower before and during TB-IRIS. By receiver operating curve analysis, CXCL10, and/or interleukin-18 pre-ART were predictive of TB-IRIS. Plasma interleukin-18 levels pre-ART are candidate biomarkers for predicting paradoxical and unmasking TB-IRIS and should be investigated for risk stratification and elucidation of disease pathogenesis.

  4. [Nosology of inflammatory diseases: lessons learned from the auto-inflammatory syndromes--a focus on skin manifestations].

    PubMed

    Lipsker, Dan; Ramot, Yuval; Ingber, Arieh

    2012-10-01

    Auto-inflammatory diseases were first described more than 10 years ago as inherited disorders, characterized by recurrent flares of inflammation due to an abnormality in the innate immune system. The understanding of the underlying pathogenic mechanisms of these disorders, and especially the fact that they are mediated by IL-1 secretion by stimulated monocytes/macrophages, facilitated significant progress in patient management. IL-1 inhibitors are especially effective, and indeed, a brief and complete response to IL-1 inhibition is probably one of the best signs of auto-inflammation. Cutaneous manifestations are frequent in the monogenic auto-inflammatory syndromes, and a careful analysis of those findings reveals that they are almost always the consequence of neutrophilic skin infiltration. The neutrophilic dermatoses are, therefore, the cutaneous manifestations of those disorders. Even when the neutrophilic dermatoses occur outside the setting of genetically determined auto-inflammatory disorders, they probably also result from auto-inflammatory mechanisms. The distinction between auto-inflammation and autoimmunity is essential for the proper treatment of the patients. Auto-inflammation will almost always respond to IL-1 inhibition, while immunospressors will not be beneficial. The aim of the current paper is to review these two sub-groups of inflammatory diseases, focusing on their cutaneous manifestations, and highlighting the connection between these syndromes and inflammation in general.

  5. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome.

    PubMed

    Bhatia, Madhav; Moochhala, Shabbir

    2004-02-01

    Inflammatory response leading to organ dysfunction and failure continues to be the major problem after injury in many clinical conditions such as sepsis, severe burns, acute pancreatitis, haemorrhagic shock, and trauma. In general terms, systemic inflammatory response syndrome (SIRS) is an entirely normal response to injury. Systemic leukocyte activation, however, is a direct consequence of a SIRS and if excessive, can lead to distant organ damage and multiple organ dysfunction syndrome (MODS). When SIRS leads to MODS and organ failure, the mortality becomes high and can be more than 50%. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is a major component of MODS of various aetiologies. Inflammatory mediators play a key role in the pathogenesis of ARDS, which is the primary cause of death in these conditions. This review summarizes recent studies that demonstrate the critical role played by inflammatory mediators such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, platelet activating factor (PAF), IL-10, granulocyte macrophage-colony stimulating factor (GM-CSF), C5a, intercellular adhesion molecule (ICAM)-1, substance P, chemokines, VEGF, IGF-I, KGF, reactive oxygen species (ROS), and reactive nitrogen species (RNS) in the pathogenesis of ARDS. It is reasonable to speculate that elucidation of the key mediators in ARDS coupled with the discovery of specific inhibitors would make it possible to develop clinically effective anti-inflammatory therapy.

  6. Natural Products: Insights into Leishmaniasis Inflammatory Response

    PubMed Central

    Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

    2015-01-01

    Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

  7. Basophils, cytokines, and the allergic inflammatory response.

    PubMed

    DuBuske, L M

    1996-01-01

    Immediate allergic response has long been recognized to be related to the activation of mast cells by antigen. The role of the mast cells as producers of cytokines, however, has only more recently been extensively studied. The effect of TH2 lymphocytes in the inflammatory process is now well recognized in animal models. The central role of cytokines in the allergic inflammatory response is currently an area of intense clinical investigation. Cytokines influence production, migration, and activation of basophils. A wide array of cytokines is produced by mast cells upon initiation of the immediate allergic response. These cytokines influence a number of other different cells including basophils and eosinophils, and also activate lymphocytes, thus perpetuating allergic inflammation.

  8. [Auto-inflammatory syndromes and pregnancy].

    PubMed

    Stankovic, Katia; Hentgen, Véronique; Grateau, Gilles

    2008-11-01

    In familial mediterranean fever (FMF), fertility is normal in treated patients. There is no abnormality of spermatogenesis under usual therapeutic doses of colchicine. The risk of early abortion is increased if inflammatory attacks occur during the pregnancy. It is recommended to continue colchicine treatment during the conception and the pregnancy. Careful follow-up must be organized, even more in patients with renal amyloidosis. Breast-feeding is allowed under colchicine with no risk for the baby. There is no indication for systematic amniocentesis in FMF patients treated with colchicine.

  9. Acute coronary syndromes as auto-inflammatory disorders.

    PubMed

    Suzuki, Makoto

    2012-01-01

    From the onset to the healing stage of acute coronary syndromes, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Even though the early reperfusion treatment either by thrombolysis or percutaneous coronary intervention provides the excellent clinical benefits in patients with acute coronary syndromes, ischemia/ reperfusion injury may somewhat offset those great advantages. Inflammation, although potentially protective, has been deeply associated with those detrimental conditions. The hexagonal vascular inflammatory network which is composed of activated various leukocytes, vascular endothelial cells, vascular smooth muscle cells, platelets, excess reactive oxygen species, and cholesterol may contribute these vicious circles. To address these complex syndromes with more benefits regarding the prevention and treatment, this review comprehensively updates the pathogenesis of acute coronary syndromes from the view points of vascular inflammation.

  10. Inflammatory monocytes hinder antiviral B cell responses

    PubMed Central

    Sammicheli, Stefano; Kuka, Mirela; Di Lucia, Pietro; de Oya, Nereida Jimenez; De Giovanni, Marco; Fioravanti, Jessica; Cristofani, Claudia; Maganuco, Carmela G.; Fallet, Benedict; Ganzer, Lucia; Sironi, Laura; Mainetti, Marta; Ostuni, Renato; Larimore, Kevin; Greenberg, Philip D.; de la Torre, Juan Carlos; Guidotti, Luca G.; Iannacone, Matteo

    2016-01-01

    Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b+Ly6Chi inflammatory monocytes. These myeloid cells were recruited to lymph nodes draining LCMV infection sites in a type I interferon-, CCR2-dependent fashion and they suppressed antiviral B cell responses by virtue of their ability to produce nitric oxide. Depletion of inflammatory monocytes, inhibition of their lymph node recruitment or impairment of their nitric oxide-producing ability enhanced LCMV-specific B cell survival and led to robust neutralizing antibody production. In conclusion, our results identify inflammatory monocytes as critical gatekeepers that prevent antiviral B cell responses and suggest that certain viruses take advantage of these cells to prolong their persistence within the host. PMID:27868108

  11. Clinical particularities and response to the anti-inflammatory effect of antiviral treatment in patients with Chronic Hepatitis C and Rheumatoid Syndrome

    PubMed Central

    Lilea, GC; Streba, CT; Baloseanu, CL; Vere, CC; Rogoveanu, I

    2012-01-01

    Hepatitis C virus (HCV) is an important cause for the development of serious hepatic disease such as chronic hepatitis and liver cirrhosis. Though the pathological mechanisms are poorly understood, it is well established that CHC plays an important role in several immune mediated conditions, including rheumatoid arthritis. We focused on the clinical particularities of patients with CHC and associated RS and we specifically investigated the anti-inflammatory role of IFN-alpha concerning the rheumatic symptoms. PMID:23346247

  12. Tuberculosis-immune reconstitution inflammatory syndrome in HIV: from pathogenesis to prediction.

    PubMed

    Gopalan, Narendran; Andrade, Bruno Bezerril; Swaminathan, Soumya

    2014-05-01

    Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is an exaggerated, dysregulated immune response against dead or viable antigens of Mycobacterium tuberculosis that frequently occurs after initiation of antiretroviral therapy despite an effective suppression of HIV viremia. Scientific advances in IRIS pathogenesis have led researchers and clinicians to postulate risk factors that could possibly predict this syndrome, in an attempt to reduce the incidence and the severity of IRIS, with appropriate anti-inflammatory therapy. This review is a summary of the available literature on pathogenic mechanisms involved from the macro to the micro level, the clinical spectrum, available predictors and the scope of these biomarkers to function as specific therapeutic targets, that could effectively modulate or ameliorate this syndrome in future.

  13. Immune profiling of BALB/C and C57BL/6 mice reveals a correlation between Ureaplasma parvum-Induced fetal inflammatory response syndrome-like pathology and increased placental expression of TLR2 and CD14.

    PubMed

    Allam, Ayman B; von Chamier, Maria; Brown, Mary B; Reyes, Leticia

    2014-03-01

    Both BALB/c and C57BL/6 mice are susceptible to intrauterine infection with Ureaplasma parvum, but only protypical TH2/M2 BALB/c mice develop severe chorioamnionitis, fetal infection, and fetal inflammatory response syndrome-like (FIRS) pathology. Microscopy, gene expression analysis, and ELISA were used to identify placental innate immune responses relevant to macrophage polarity, severe chorioamnionitis, and fetal infection. Both mouse strains exhibited a pro-M2 cytokine profile at the maternal/fetal interface. In BALB/c mice, expression of CD14 and TLRs 1, 2, 6 was increased in infected placentas; TLR2 and CD14 were localized to neutrophils. Increased TLR2/CD14 was also observed in BALB/c syncytiotrophoblasts in tissues with pathological evidence of FIRS. In contrast, expression in C57BL/6 placentas was either unchanged or down-regulated. Our findings show a link between increased syncytiotrophoblast expression of CD14/TLR2 and FIRS-like pathology in BALB/c mice. Functional studies are required to determine if CD14 is contributing to fetal morbidity during chorioamnionitis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Irritable bowel syndrome and inflammatory bowel disease: interrelated diseases?

    PubMed

    Quigley, Eamonn M M

    2005-01-01

    In the past inflammatory bowel disease (IBD), celiac disease and irritable bowel syndrome (IBS) were regarded as completely separate disorders. Now, with the description of inflammation, albeit low-grade, in IBS, and of symptom overlap between IBS and celiac disease, this contention has come under question. Is there true overlap between these disorders? Despite the limitations of available data one cannot but be struck by some areas of apparent convergence: IBD and celiac disease in remission, lymphocytic colitis and microscopic inflammation in IBS, in general, and, especially, in the post-infectious IBS category. The convergence between latent celiac disease and sub-clinical IBD, on the one hand, and IBS, on the other, appears, based on available evidence, to be somewhat spurious and may largely relate to misdiagnosis, a phenomenon which may also explain the apparent evolution of IBS into IBD in some studies. Similarities between IBS and lymphocytic colitis are more striking and less readily dismissed; as for IBS, well documented instances of progression of lymphocytic colitis to full-blown IBD are infrequent, suggesting a true separation between this disorder and classical IBD. Do IBS and lymphocytic colitis represent different responses to similar triggers? Will some of the 'inflamed' IBS subgroup be reclassified as part of the spectrum of lymphocytic colitis in the future? Will inflammation emerge as a common underlying factor in the pathogenesis of IBS? The answer to these and many questions must await further study of this fascinating area.

  15. Simultaneous Combined Myositis, Inflammatory Polyneuropathy, and Overlap Myasthenic Syndrome

    PubMed Central

    Magy, Laurent; Corcia, Philippe; Ghorab, Karima; Richard, Laurence; Ciron, Jonathan; Duchesne, Mathilde; Vallat, Jean-Michel

    2016-01-01

    Immune-mediated neuromuscular disorders include pathologies of the peripheral nervous system, neuromuscular junction, and muscles. If overlap syndromes (or the association of almost two autoimmune disorders) are recognized, the simultaneous occurrence of several autoimmune neuromuscular disorders is rare. We describe two patients presenting the simultaneous occurrence of inflammatory neuropathy, myositis, and myasthenia gravis (with positive acetylcholine receptor antibodies). For each patient, we carried out a pathological analysis (nerve and muscle) and an electrophysiological study (and follow-up). To our knowledge, this is the first description of such a triple immune-mediated neuromuscular syndrome. We compared our observations with a few other cases of simultaneous diagnosis of two inflammatory neuromuscular disorders. PMID:28044116

  16. Analyzing inflammatory response as excitable media

    NASA Astrophysics Data System (ADS)

    Yde, Pernille; Høgh Jensen, Mogens; Trusina, Ala

    2011-11-01

    The regulatory system of the transcription factor NF-κB plays a great role in many cell functions, including inflammatory response. Interestingly, the NF-κB system is known to up-regulate production of its own triggering signal—namely, inflammatory cytokines such as TNF, IL-1, and IL-6. In this paper we investigate a previously presented model of the NF-κB, which includes both spatial effects and the positive feedback from cytokines. The model exhibits the properties of an excitable medium and has the ability to propagate waves of high cytokine concentration. These waves represent an optimal way of sending an inflammatory signal through the tissue as they create a chemotactic signal able to recruit neutrophils to the site of infection. The simple model displays three qualitatively different states; low stimuli leads to no or very little response. Intermediate stimuli leads to reoccurring waves of high cytokine concentration. Finally, high stimuli leads to a sustained high cytokine concentration, a scenario which is toxic for the tissue cells and corresponds to chronic inflammation. Due to the few variables of the simple model, we are able to perform a phase-space analysis leading to a detailed understanding of the functional form of the model and its limitations. The spatial effects of the model contribute to the robustness of the cytokine wave formation and propagation.

  17. Electronic cigarette exposure triggers neutrophil inflammatory responses.

    PubMed

    Higham, Andrew; Rattray, Nicholas J W; Dewhurst, Jennifer A; Trivedi, Drupad K; Fowler, Stephen J; Goodacre, Royston; Singh, Dave

    2016-05-17

    The use of electronic cigarettes (e-cigs) is increasing and there is widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research is needed to evaluate the safety of e-cig use. Our aim was to investigate the effects of e-cigs on the inflammatory response of human neutrophils. Neutrophils were exposed to e-cig vapour extract (ECVE) and the expression of CD11b and CD66b was measured by flow cytometry and MMP-9 and CXCL8 by ELISA. We also measured the activity of neutrophil elastase (NE) and MMP-9, along with the activation of inflammatory signalling pathways. Finally we analysed the biochemical composition of ECVE by ultra-high performance liquid chromatography mass spectrometry. ECVE caused an increase in the expression of CD11b and CD66b, and increased the release of MMP-9 and CXCL8. Furthermore, there was an increase in NE and MMP-9 activity and an increase in p38 MAPK activation. We also identified several harmful chemicals in ECVE, including known carcinogens. ECVE causes a pro-inflammatory response from human neutrophils. This raises concerns over the safety of e-cig use.

  18. Collective cell migration during inflammatory response

    NASA Astrophysics Data System (ADS)

    Wu, Di; Stroka, Kimberly; Aranda-Espinoza, Helim

    2012-02-01

    Wound scratch healing assays of endothelial cell monolayers is a simple model to study collective cell migration as a function of biological signals. A signal of particular interest is the immune response, which after initial wounding in vivo causes the release of various inflammatory factors such as tumor necrosis alpha (TNF-α). TNF-α is an innate inflammatory cytokine that can induce cell growth, cell necrosis, and change cell morphology. We studied the effects of TNF-α on collective cell migration using the wound healing assays and measured several migration metrics, such as rate of scratch closure, velocities of leading edge and bulk cells, closure index, and velocity correlation functions between migrating cells. We observed that TNF-α alters all migratory metrics as a function of the size of the scratch and TNF-α content. The changes observed in migration correlate with actin reorganization upon TNF-α exposure.

  19. Crusted scabies-associated immune reconstitution inflammatory syndrome.

    PubMed

    Fernández-Sánchez, Mónica; Saeb-Lima, Marcela; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

    2012-11-26

    Despite the widely accepted association between crusted scabies and human immunodeficiency virus (HIV)-infection, crusted scabies has not been included in the spectrum of infections associated with immune reconstitution inflammatory syndrome in HIV-infected patients initiating antiretroviral therapy. We report a case of a 28-year-old Mexican individual with late HIV-infection, who had no apparent skin lesions but soon after initiation of antiretroviral therapy, he developed an aggressive form of crusted scabies with rapid progression of lesions. Severe infestation by Sarcoptes scabiei was confirmed by microscopic examination of the scale and skin biopsy. Due to the atypical presentation of scabies in a patient responding to antiretroviral therapy, preceded by no apparent skin lesions at initiation of antiretroviral therapy, the episode was interpreted for the first time as "unmasking crusted scabies-associated immune reconstitution inflammatory syndrome". This case illustrates that when crusted scabies is observed in HIV-infected patients responding to antiretroviral therapy, it might as well be considered as a possible manifestation of immune reconstitution inflammatory syndrome. Patient context should be considered for adequate diagnosis and treatment of conditions exacerbated by antiretroviral therapy-induced immune reconstitution.

  20. Direct molecular detection of pathogens in blood as specific rule-in diagnostic biomarker in patients with presumed sepsis: our experience on a heterogeneous cohort of patients with signs of infective systemic inflammatory response syndrome.

    PubMed

    Avolio, Manuela; Diamante, Paola; Modolo, Maria Luisa; De Rosa, Rita; Stano, Paola; Camporese, Alessandro

    2014-08-01

    The practical value of blood cultures in the diagnosis of sepsis is impaired by a delay in the turnaround time to result and by the fact that blood culture positive can be found for only about 30% of these patients. Conventional laboratory signs of sepsis and acute phase protein biomarkers are sensitive and easy to use, but often also very nonspecific. Molecular diagnostic reflects currently the most promising avenue to decrease time to result and to influence decision making for antibiotic therapy in the septic host. In this study, we wish to highlight the impact of the LightCycler SeptiFast, a multipathogen probe-based real-time polymerase chain reaction, in the rapid etiological diagnosis of sepsis in patients with clinical and laboratory signs of bloodstream infections. We have evaluated prospectively 830 adult patients with suspected bloodstream infection and at least two criteria of systemic inflammatory response syndrome. In more than 50% of critically ill patients strongly suspected of having sepsis, we arrived to an etiological diagnosis only by the molecular method in a median time of 15 h, with specificity and predictive positive values of 96% and 94%, respectively. We highlight the role of DNAemia as time-critical, high-specificity, etiological, non-culture-based rule-in diagnostic biomarker in patients with presumed sepsis.

  1. Thiamine responsive megaloblastic anemia syndrome.

    PubMed

    Ganesh, Ramaswamy; Ezhilarasi, S; Vasanthi, Thiruvengadam; Gowrishankar, Kalpana; Rajajee, Sarala

    2009-03-01

    Thiamine responsive megaloblastic anemia syndrome (TRMA) is a clinical triad characterized by thiamine-responsive anemia, diabetes mellitus and sensorineural deafness. We report a 4-year-old girl with TRMA whose anemia improved following administration of thiamine and this case report sensitizes the early diagnosis and treatment with thiamine in children presenting with anemia, diabetes and deafness.

  2. Scorpion Venom and the Inflammatory Response

    PubMed Central

    Petricevich, Vera L.

    2010-01-01

    Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability. PMID:20300540

  3. PDT-induced inflammatory and host responses.

    PubMed

    Firczuk, Małgorzata; Nowis, Dominika; Gołąb, Jakub

    2011-05-01

    Photodynamic therapy (PDT) is used in the management of neoplastic and nonmalignant diseases. Its unique mechanisms of action include direct cytotoxic effects exerted towards tumor cells, destruction of tumor and peritumoral vasculature and induction of local acute inflammatory reaction. The latter develops in response to (1) damage to tumor and stromal cells that leads to the release of cell death-associated molecular patterns (CDAMs) or damage associated molecular patterns (DAMPs), (2) early vascular changes that include increased vascular permeability, vascular occlusion, and release of vasoactive and proinflammatory mediators, (3) activation of alternative pathway of complement leading to generation of potent chemotactic factors, and (4) induction of signaling cascades and transcription factors that trigger secretion of cytokines, matrix metalloproteinases, or adhesion molecules. The majority of studies indicate that induction of local inflammatory response contributes to the antitumor effects of PDT and facilitates development of systemic immunity. However, the degree of PDT-induced inflammation and its subsequent contribution to its antitumor efficacy depend on multiple parameters, such as chemical nature, concentration and subcellular localization of the photosensitizers, the spectral characteristics of the light source, light fluence and fluence rate, oxygenation level, and tumor type. Identification of detailed molecular mechanisms and development of therapeutic approaches modulating PDT-induced inflammation will be necessary to tailor this treatment to particular clinical conditions.

  4. Inflammatory responses to infection: the Dutch contribution.

    PubMed

    Nolte, Martijn A; van der Meer, Jos W M

    2014-12-01

    At any given moment, our body is under attack by a large variety of pathogens, which aim to enter and use our body to propagate and disseminate. The extensive cellular and molecular complexity of our immune system enables us to efficiently eliminate invading pathogens or at least develop a condition in which propagation of the microorganism is reduced to a minimum. Yet, the evolutionary pressure on pathogens to circumvent our immune defense mechanisms is immense, which continuously leads to the development of novel pathogenic strains that challenge the health of mankind. Understanding this battle between pathogen and the immune system has been a fruitful area of immunological research over the last century and will continue to do so for many years. In this review, which has been written on the occasion of the 50th anniversary of the Dutch Society for Immunology, we provide an overview of the major contributions that Dutch immunologists and infection biologists have made in the last decades on the inflammatory response to viral, bacterial, fungal or parasitic infections. We focus on those studies that have addressed both the host and the pathogen, as these are most interesting from an immunological point of view. Although it is not possible to completely cover this comprehensive research field, this review does provide an interesting overview of Dutch research on inflammatory responses to infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. 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

  6. Crusted scabies-associated immune reconstitution inflammatory syndrome

    PubMed Central

    2012-01-01

    Background Despite the widely accepted association between crusted scabies and human immunodeficiency virus (HIV)-infection, crusted scabies has not been included in the spectrum of infections associated with immune reconstitution inflammatory syndrome in HIV-infected patients initiating antiretroviral therapy. Case presentation We report a case of a 28-year-old Mexican individual with late HIV-infection, who had no apparent skin lesions but soon after initiation of antiretroviral therapy, he developed an aggressive form of crusted scabies with rapid progression of lesions. Severe infestation by Sarcoptes scabiei was confirmed by microscopic examination of the scale and skin biopsy. Due to the atypical presentation of scabies in a patient responding to antiretroviral therapy, preceded by no apparent skin lesions at initiation of antiretroviral therapy, the episode was interpreted for the first time as “unmasking crusted scabies-associated immune reconstitution inflammatory syndrome”. Conclusion This case illustrates that when crusted scabies is observed in HIV-infected patients responding to antiretroviral therapy, it might as well be considered as a possible manifestation of immune reconstitution inflammatory syndrome. Patient context should be considered for adequate diagnosis and treatment of conditions exacerbated by antiretroviral therapy-induced immune reconstitution. PMID:23181485

  7. Changing outcome in inflammatory neuropathies: Rasch-comparative responsiveness.

    PubMed

    Draak, Thomas H P; Vanhoutte, Els K; van Nes, Sonja I; Gorson, Kenneth C; Van der Pol, W Ludo; Notermans, Nicolette C; Nobile-Orazio, Eduardo; Léger, Jean-Marc; Van den Bergh, Peter Y K; Lauria, Giuseppe; Bril, Vera; Katzberg, Hans; Lunn, Michael P T; Pouget, Jean; van der Kooi, Anneke J; Hahn, Angelika F; Doorn, Pieter A van; Cornblath, David R; van den Berg, Leonard H; Faber, Catharina G; Merkies, Ingemar S J

    2014-12-02

    We performed responsiveness comparison between the patient-reported Inflammatory Rasch-built Overall Disability Scale (I-RODS) and the widely used clinician-reported Inflammatory Neuropathy Cause and Treatment-Overall Neuropathy Limitation Scale (INCAT-ONLS) in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and immunoglobulin M-monoclonal gammopathy of undetermined significance related polyneuropathy (IgM-MGUSP). One hundred thirty-seven patients (GBS: 55, CIDP: 59, IgM-MGUSP: 23) with a new diagnosis or clinical relapse assessed both scales. Patients with GBS/CIDP were examined at 0, 1, 3, 6, and 12 months; patients with IgM-MGUSP at 0, 3, and 12. We subjected all data to Rasch analyses, and calculated for each patient the magnitude of change on both scales using the minimal clinically important difference (MCID) related to the individual standard errors (SEs). A responder was defined as having an MCID-SE ≥1.96. Individual scores on both measures were correlated with the EuroQoL thermometer (heuristic responsiveness). The I-RODS showed a significantly higher proportion of meaningful improvement compared with the INCAT-ONLS findings in GBS/CIDP. For IgM-MGUSP, the lack of responsiveness during the 1-year study did not allow a clear separation. Heuristic responsiveness was consistently higher with the I-RODS. The I-RODS more often captures clinically meaningful changes over time, with a greater magnitude of change, compared with the INCAT-ONLS disability scale in patients with GBS and CIDP. The I-RODS offers promise for being a more sensitive measure and its use is therefore suggested in future trials involving patients with GBS and CIDP. © 2014 American Academy of Neurology.

  8. Plasma inflammatory cytokines correlate to the ovarian hyperstimulation syndrome.

    PubMed

    Abramov, Y; Schenker, J G; Lewin, A; Friedler, S; Nisman, B; Barak, V

    1996-07-01

    The objective of this study was to follow the kinetics of four inflammatory cytokines in the plasma and ascitic fluid of seven patients who developed severe ovarian hyperstimulation syndrome (OHSS) after induction of ovulation for in-vitro fertilization. Blood samples were obtained from these patients at three different times: upon hospitalization; when significant clinical improvement was evident; and after complete resolution. Samples were analysed for interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-alpha). Ascitic fluid was obtained by therapeutic paracentesis from all study patients during the active phase and analysed for these cytokines. Two control groups were available: the first included 15 women undergoing controlled ovarian stimulation for in-vitro fertilization without developing OHSS, while the second consisted of 25 healthy women not undergoing ovulation induction or any other medical treatment. High concentrations of IL-1, IL-6 and TNF-alpha were detected in all individuals upon admission for severe OHSS. Concentrations dropped significantly along with clinical improvement, reaching normal values after complete resolution. A statistically significant correlation was found between plasma cytokine concentrations and certain biological characteristics of the syndrome such as leukocytosis, increased haematocrit, and elevated plasma 17-beta-oestradiol concentrations. Ascitic fluid obtained from the study patients contained high IL-6 and IL-8 concentrations, while other cytokines were unaltered. These results suggest close association between inflammatory cytokines and the pathophysiology of the ovarian hyperstimulation syndrome.

  9. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome

    USGS Publications Warehouse

    Meteyer, Carol U.; Barber, Daniel; Mandl, Judith N.

    2012-01-01

    White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS), which was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.

  10. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome.

    PubMed

    Meteyer, Carol U; Barber, Daniel; Mandl, Judith N

    2012-11-15

    White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.

  11. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome

    PubMed Central

    Meteyer, Carol U.; Barber, Daniel; Mandl, Judith N.

    2012-01-01

    White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology. PMID:23154286

  12. Association of a dietary inflammatory index with inflammatory indices and metabolic syndrome among police officers.

    PubMed

    Wirth, Michael D; Burch, James; Shivappa, Nitin; Violanti, John M; Burchfiel, Cecil M; Fekedulegn, Desta; Andrew, Michael E; Hartley, Tara A; Miller, Diane B; Mnatsakanova, Anna; Charles, Luenda E; Steck, Susan E; Hurley, Thomas G; Vena, John E; Hébert, James R

    2014-09-01

    To determine whether the dietary inflammatory index (DII) is associated with inflammatory or metabolic biomarkers and metabolic syndrome (MetSyn) among police officers. Cross-sectional data from the Buffalo Cardio-Metabolic Occupational Police Stress study were derived from saliva and fasting blood samples, anthropometric measurements, long-term shiftwork histories, and demographic, stress/depression, and food frequency questionnaires (FFQs). Metabolic syndrome was defined using standard criteria. Officers in DII quartiles 2 to 4 were more likely to exceed a threshold of 3.0 mg/L for C-reactive protein (odds ratio [OR] = 1.88; 95% confidence interval [95% CI] = 1.02 to 3.45; OR = 2.17; 95% CI = 1.19 to 3.95; OR = 1.57; 95% CI = 0.85 to 2.88, respectively) compared with quartile 1. The glucose intolerance component of MetSyn was more prevalent among officers in DII quartile 4 than among those in quartile 1 (OR = 2.03; 95% CI = 1.08 to 3.82). A pro-inflammatory diet was associated with elevated CRP and with the glucose intolerance component of MetSyn.

  13. Type I lepra reaction presenting as immune reconstitution inflammatory syndrome.

    PubMed

    Kharkar, Vidya; Bhor, Urmila H; Mahajan, Sunanda; Khopkar, Uday

    2007-01-01

    Immune reconstitution inflammatory syndrome (IRIS) is an unusual inflammatory reaction due to infectious and non-infectious causes occurring in human Immunodeficiency virus (HIV)-infected patients. IRIS occurs after the initiation of antiretroviral therapy. There are no reports of type I lepra reaction due to IRIS in published literature from India. We report two cases of HIV-infected males who presented with borderline tuberculoid leprosy in type 1 reaction after the initiation of highly active antiretroviral treatment (HAART). Case 1 presented with multiple, tender, erythematous and hypoesthetic plaques on the trunk and extremities after 3 months of antiretroviral therapy. In case 2, type I lepra reaction was observed 2 months after the initiation of HAART.

  14. Transport induced inflammatory responses in horses.

    PubMed

    Wessely-Szponder, J; Bełkot, Z; Bobowiec, R; Kosior-Korzecka, U; Wójcik, M

    2015-01-01

    Deleterious response to road transport is an important problem in equine practice. It determines different physiological, immunological and metabolic changes which lead to increased susceptibility to several disorders such as pneumonia, diarrhea, colics, laminitis, injuries and rhabdomyolisis. The aim of our study was to look for possible relationships between transportation of female young and older horses over a long and short distance and an inflammatory state reflected by an increase of acute phase protein concentration, oxidative stress and muscle injury. The study was conducted on 24 cold-blooded female horses divided into four groups. Six fillies aged 6-18 months and six mares aged 10-12 years were transported over the distance of about 550 km, six fillies aged 6-18 months and six mares aged 10-12 years were transported over the distance of about 50 km. Plasma and serum were obtained from blood samples taken before transportation (T0), immediately after transportation (T1) and at an abattoir during slaughter (T2). In these samples fibrinogen, MDA, AST and CK were assessed. Fibrinogen increased in all studied groups especially in fillies after long distance transportation, where it reached 205±7.07 mg/dl before transportation, 625±35.35 mg/dl after transportation, and 790±14.14 mg/dl during slaughter. MDA concentrations rose after transportation and reached the maximal level during slaughter. CK activity was more elevated after short transportation in younger horses, whereas initial activity of AST was higher in older horses. We estimated that intensified responses from acute phase, oxidative stress and muscle injury parameters indicated an inflammatory state.

  15. Inflammatory response in transapical transaortic valve replacement.

    PubMed

    Goetzenich, A; Roehl, A; Spillner, J; Haushofer, M; Dohmen, G; Tewarie, L; Moza, A

    2011-12-01

    Transapical aortic valve implantation (TA-AVI) has become a fast growing alternative to conventional aortic valve replacement (cAVR) particularly for patients burdened with serious comorbidities. We investigated whether the inflammatory response triggered by TA-AVI reflects the less invasive nature of this procedure. In this prospective observational study 25 patients undergoing aortic valve replacement (AVR; 15 cAVR and 10 TA-AVI) were included. Serial plasma cytokine concentrations (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunosorbent assay kits at six different time points before, during, and after surgery. Plasma levels of all three cytokines increased during and after both procedures and returned to baseline before the patient's discharge. Peak values of IL-6 were 258 ± 113 pg/mL in AVR patients versus 111 ± 101 pg/mL in TA-AVI patients and were reached 12 hours after surgery. For IL-8, peak values were 51 ± 29 pg/mL 1 hour after surgery in AVR patients versus 15 ± 20 pg/mL on wound closure in TA-AVI patients. Plasma levels of IL-6 and IL-8 were significantly reduced in the TA-AVI group as compared with cAVR. IL-10 is markedly activated in both groups yet its induction is more prominent in AVR patients with peak values of 51 ± 28 pg/mL for AVR versus 24 ± 18 pg/mL for TA-AVI on wound closure. TA-AVI compared with cAVR results in a significant reduction but not elimination of a systemic inflammatory response, which is attributable to cardiopulmonary bypass-dependent and bypass-independent factors. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Multiphasic and multifocal cryptococcal immune reconstitution inflammatory syndrome in an HIV-infected patient: interplay of infection and immunity.

    PubMed

    Katchanov, Juri; Zimmermann, Ulrike; Branding, Gordian; Tintelnot, Kathrin; Müller, Markus; Arastéh, Keikawus; Stocker, Hartmut

    2014-01-01

    We report a case of cryptococcal immune reconstitution inflammatory syndrome affecting the lungs, and 10 months later the cervical lymph nodes, in the absence of cryptococcal meningitis, in advanced HIV infection. Our report demonstrates the organ-specificity of the timing of the inflammatory response and illustrates the organ-specific interplay of immunity and infection in cryptococcal disease. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. The role of whole blood impedance aggregometry and its utilisation in the diagnosis and prognosis of patients with systemic inflammatory response syndrome and sepsis in acute critical illness.

    PubMed

    Davies, Gareth R; Mills, Gavin M; Lawrence, Matthew; Battle, Ceri; Morris, Keith; Hawkins, Karl; Williams, Phylip Rhodri; Davidson, Simon; Thomas, Dafydd; Evans, Phillip Adrian

    2014-01-01

    To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count). We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p = 0.001, Collagen 102.6±33.0 vs 79.1±38.8; p = 0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p = 0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)). Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant.

  18. Infevers: an evolving mutation database for auto-inflammatory syndromes.

    PubMed

    Touitou, Isabelle; Lesage, Suzanne; McDermott, Michael; Cuisset, Laurence; Hoffman, Hal; Dode, Catherine; Shoham, Nitza; Aganna, Ebun; Hugot, Jean-Pierre; Wise, Carol; Waterham, Hans; Pugnere, Denis; Demaille, Jacques; Sarrauste de Menthiere, Cyril

    2004-09-01

    The Infevers database (http://fmf.igh.cnrs.fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (FMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is FMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation.

  19. Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

    SciTech Connect

    Duan, Erzhen; Wang, Dang; Luo, Rui; Luo, Jingyi; Gao, Li; Chen, Huanchun; Fang, Liurong Xiao, Shaobo

    2014-11-15

    The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. - Highlights: • PRRSV infection triggers HMGB1 release from MARC-145 cells and PAMs. • HMGB1 does not significantly affect PRRSV proliferation. • HMGB1 is involved in PRRSV-induced NF-κB activation and inflammatory responses. • HMGB1 promotes PRRSV-induced inflammatory responses through TLR2/4 and RAGE.

  20. Irritable bowel syndrome in quiescent inflammatory bowel disease: a review.

    PubMed

    Burgell, R E; Asthana, A K; Gibson, P R

    2015-12-01

    Ongoing troublesome bowel symptoms despite quiescent inflammatory disease are a frequent management challenge when caring for patients with inflammatory bowel disease (IBD). Even when active disease has been excluded the prevalence of residual gastrointestinal symptoms is surprisingly high and the cause often obscure. The presence of a concurrent functional disorder such as irritable bowel syndrome (IBS) is associated with worse quality of life, worse physical functioning, higher prevalence of anxiety and greater health care utilization. Potential etiological mechanisms leading to the development of IBS like symptoms include the development of visceral hypersensitivity following the original inflammatory insult, alteration in cortical processing, dysbiosis and residual subacute inflammation. Therapeutic options for managing IBS in patients with IBD include dietary modification, interventions targeted at correction of visceral sensory dysfunction or cortical processing and modulation of the gut microbiota. As there are few studies specifically examining the treatment of IBS in patients with IBD, the majority of therapeutic interventions are extrapolated from the IBS literature. Given the frequency of residual functional symptoms in IBS, significantly more research is warranted in this field.

  1. Paradoxical Reactions and the Immune Reconstitution Inflammatory Syndrome.

    PubMed

    Church, L W Preston; Chopra, Amit; Judson, Marc A

    2017-03-01

    In HIV-infected individuals, paradoxical reactions after the initiation of antiretroviral therapy (ART) are associated with a variety of underlying infections and have been called the immune reconstitution inflammatory syndrome (IRIS). In cases of IRIS associated with tuberculosis (TB), two distinct patterns of disease are recognized: (i) the progression of subclinical TB to clinical disease after the initiation of ART, referred to as unmasking, and (ii) the progression or appearance of new clinical and/or radiographic disease in patients with previously recognized TB after the initiation of ART, the classic or "paradoxical" TB-IRIS. IRIS can potentially occur in all granulomatous diseases, not just infectious ones. All granulomatous diseases are thought to result from interplay of inflammatory cells and mediators. One of the inflammatory cells thought to be integral to the development of the granuloma is the CD4 T lymphocyte. Therefore, HIV-infected patients with noninfectious granulomatous diseases such as sarcoidosis may also develop IRIS reactions. Here, we describe IRIS in HIV-infected patients with TB and sarcoidosis and review the basic clinical and immunological aspects of these phenomena.

  2. Chronic Inflammatory Disease, Lifestyle and Treatment Response

    ClinicalTrials.gov

    2017-05-30

    Autoimmune Diseases; Inflammatory Bowel Diseases; Crohn Disease (CD); Colitis, Ulcerative (UC); Arthritis, Rheumatoid (RA); Spondylarthropathies; Arthritis, Psoriatic (PsA); Psoriasis; Hidradenitis Suppurativa (HS); Uveitis

  3. Metabolic Syndrome and Selective Inflammatory Markers in Psoriatic Patients

    PubMed Central

    Vachatova, Simona; Andrys, Ctirad; Salavec, Miloslav; Ettler, Karel; Rehacek, Vit; Cermakova, Eva; Malkova, Andrea

    2016-01-01

    The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI (p < 0.05) and diastolic blood pressure (p < 0.05) in the psoriatic patients. The values of waist circumference and BMI were significantly higher (p < 0.05) in the male patients compared to the men in the control group. The analysis revealed significantly higher CRP (p < 0.001), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.01) levels in the psoriatic patients. Significantly higher levels of CRP (p < 0.01), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.05) were found in the patients with MS compared to the controls with MS. The level of adiponectin was significantly lower (p < 0.01) in the patients with MS. Finally, we found significantly higher level of Lp-PLA2 (p < 0.001) in the group of patients without MS compared to the controls without MS. In conclusion, observed inflammatory and anti-inflammatory markers (CRP, adiponectin, leptin, resistin, and Lp-PLA2) are involved in both pathogenesis of MS and pathogenesis of psoriasis. The level of Lp-PLA2 indicates the presence of subclinical atherosclerosis (cardiovascular risk) in psoriatic patients. PMID:28097156

  4. Autoimmune or auto-inflammatory syndrome induced by adjuvants (ASIA): old truths and a new syndrome?

    PubMed

    Meroni, Pier Luigi

    2011-02-01

    There has been considerable interest in the role of environmental factors and the induction of autoimmunity and the ways by which they facilitate loss of tolerance. Clearly both genetic and environmental factors are incriminated, as evidenced by the lack of concordance in identical twins and the relatively recent identification of the shared epitope in rheumatoid arthritis. In this issue a new syndrome called 'Asia'-autoimmune/auto-inflammatory syndrome induced by adjuvants has been proposed. It is an intriguing issue and one that is likely to be provocative and lead to further biologic and molecular investigations.

  5. Inflammatory response to nano- and microstructured hydroxyapatite.

    PubMed

    Mestres, Gemma; Espanol, Montserrat; Xia, Wei; Persson, Cecilia; Ginebra, Maria-Pau; Ott, Marjam Karlsson

    2015-01-01

    The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal morphologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact) and also in extracts i.e. media modified by the material (indirect contact). Additionally, the effect of supplementing the extracts with calcium ions and/or proteins was investigated. Macrophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate's microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate-like crystals substrates compared to the almost non-existent release on needle-like substrates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials.

  6. Inflammatory Response to Nano- and Microstructured Hydroxyapatite

    PubMed Central

    Mestres, Gemma; Espanol, Montserrat; Xia, Wei; Persson, Cecilia; Ginebra, Maria-Pau; Ott, Marjam Karlsson

    2015-01-01

    The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal morphologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact) and also in extracts i.e. media modified by the material (indirect contact). Additionally, the effect of supplementing the extracts with calcium ions and/or proteins was investigated. Macrophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate’s microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate-like crystals substrates compared to the almost non-existent release on needle-like substrates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials. PMID:25837264

  7. Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome

    PubMed Central

    Ganda, Anjali; Lin, Jeffrey; Onat, Duygu; Harxhi, Ante; Iyasere, Julia E.; Uriel, Nir; Cotter, Gad

    2013-01-01

    Although inflammation is a physiologic response designed to protect us from infection, when unchecked and ongoing it may cause substantial harm. Both chronic heart failure (CHF) and chronic kidney disease (CKD) are known to cause elaboration of several pro-inflammatory mediators that can be detected at high concentrations in the tissues and blood stream. The biologic sources driving this chronic inflammatory state in CHF and CKD are not fully established. Traditional sources of inflammation include the heart and the kidneys which produce a wide range of proinflammatory cytokines in response to neurohormones and sympathetic activation. However, growing evidence suggests that non-traditional biomechanical mechanisms such as venous and tissue congestion due to volume overload are also important as they stimulate endotoxin absorption from the bowel and peripheral synthesis and release of proinflammatory mediators. Both during the chronic phase and, more rapidly, during acute exacerbations of CHF and CKD, inflammation and congestion appear to amplify each other resulting in a downward spiral of worsening cardiac, vascular, and renal functions that may negatively impact patients’ outcome. Anti-inflammatory treatment strategies aimed at attenuating end organ damage and improving clinical prognosis in the cardiorenal syndrome have been disappointing to date. A new therapeutic paradigm may be needed, which involves different anti-inflammatory strategies for individual etiologies and stages of CHF and CKD. It may also include specific (short-term) anti-inflammatory treatments that counteract inflammation during the unsettled phases of clinical decompensation. Finally, it will require greater focus on volume overload as an increasingly significant source of systemic inflammation in the cardiorenal syndrome. PMID:21688186

  8. Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case–control study

    PubMed Central

    Henry, N L; Pchejetski, D; A'Hern, R; Nguyen, A T; Charles, P; Waxman, J; Li, L; Storniolo, A M; Hayes, D F; Flockhart, D A; Stearns, V; Stebbing, J

    2010-01-01

    Background: The aromatase inhibitor (AI)-associated musculoskeletal syndrome (AIMSS) occurs in approximately 50% of AI-treated patients. Inflammatory mediators are associated with oestrogen signalling and may change with oestrogen depletion. We hypothesised that AIMSS may be associated with changes in circulating inflammatory markers. Methods: Patients with breast cancer were enroled in a trial of adjuvant AI therapy. Changes in pain and function during therapy were assessed prospectively. We selected 30 cases with AIMSS and 22 controls without AIMSS, matched for demographics and prior therapy. Serum samples collected at baseline and during treatment were assayed for multiple inflammatory cytokines and lipid mediators using multiplex assays. Results: Before AI therapy, mean serum concentrations of 6 of 36 assayed factors were statistically significantly lower in cases than controls (all P<0.003). No statistically significant changes during AI therapy relative to pre-treatment were observed between cases and controls for any of the inflammatory markers tested. Conclusion: AIMSS is probably not associated with a systemic inflammatory response. Pre-treatment cytokine levels may predict for development of AIMSS. PMID:20606683

  9. In vitro effects of emodin on peritoneal macrophages that express membrane-bound CD14 protein in a rat model of severe acute pancreatitis/systemic inflammatory response syndrome.

    PubMed

    Ni, Qingqiang; Sun, Kang; Chen, Guoyue; Shang, Dong

    2014-01-01

    Emodin is the main active constituent of rhubarb and is often used in Chinese herbal medicine for the treatment of systemic inflammatory response syndrome (SIRS). The present study aimed to determine the in vitro effects of emodin on the expression of membrane-bound cluster of differentiation 14 (mCD14) protein in peritoneal macrophages (pMΦs). The severe acute pancreatitis (SAP)̸SIRS model was established in Sprague‑Dawley (SD) rats via retrograde injection of 1.5% sodium deoxycholate into the common biliopancreatic duct. The 40 SD rats were randomly divided into the sham‑operated (n=10) group (SO) and the model group (n=30). After 24 h, pMΦs were harvested and the model group was randomly divided into three subgroups (n=10 per group), the 5 µg/ml emodin group (EMO), the 0.1 µmol/ml dexamethasone group (DEX) and the SIRS/SAP group (SI). Treatment agents were administered following macrophage adhesion for 24 h. Compared with that of the SO group, the SI group showed significantly increased pathological changes (P<0.01). Compared with that of the SO group, mCD14 expression in pMΦs was significantly decreased in the SI group (P<0.01). Additionally, compared with that of the SI group, mCD14 expression in pMΦs was significantly increased in the EMO group (P<0.01) and in the DEX group (P<0.01). Compared with that of the DEX group, mCD14 expression in pMΦs was significantly increased in the EMO group (25.60±2.79 vs. 20.87±1.99; P<0.01). The pathological changes observed in the pancreas of rats in the model groups were more severe than that of the SO group. Moreover, mCD14 expression levels in pMΦs were significantly decreased in the SI group. The pathological changes of each intervention group improved to various degrees, particularly in the EMO group.

  10. Sepsis, systemic inflammatory response, and multiple organ dysfunction: the mystery continues.

    PubMed

    Fry, Donald E

    2012-01-01

    Human sepsis is thought to be systemic inflammatory response syndrome (SIRS) that is activated by invasive infection. The multiple organ dysfunction syndrome (MODS) is the identified failure of critical organ function in patients that have sustained SIRS. Because SIRS and MODS are consequences of the excessive activation of inflammation, extensive research and numerous clinical trials have pursued treatments that would modify the inflammatory response. This presentation reviews the normal local mechanisms of inflammation and provides a theoretical framework for the transition of the inflammatory process to a systemic level. Clinical trials with biomodulators to block or inhibit inflammation have generally failed to improve the outcomes in patients with severe sepsis, septic shock, and MODS. The role of counter-inflammatory signaling and the newer concept of the cholinergic anti-inflammatory pathway are being investigated, and newer hypotheses are focusing upon the balancing of proinflammatory and counter-inflammatory mechanisms as important directions for newer therapies. It is concluded that failure to define novel and effective treatments reflects fundamental gaps in our understanding of inflammation and its regulation.

  11. Cystic endometrial hyperplasia-pyometra syndrome in bitches: identification of hemodynamic, inflammatory, and cell proliferation changes.

    PubMed

    Veiga, Gisele Almeida Lima; Miziara, Ricardo Henrique; Angrimani, Daniel Souza Ramos; Papa, Paula Carvalho; Cogliati, Bruno; Vannucchi, Camila Infantosi

    2017-01-01

    Cystic endometrial hyperplasia (CEH)-pyometra syndrome is one of the most common diseases of noncastrated female dogs. However, determination of etiological mechanisms and differential diagnosis of CEH-pyometra syndrome are undefined. The aim of this study is to compare immunohistochemically the expression of cyclooxygenase-2 (COX-2) inflammatory mediator, Ki-67 antigen proliferation marker, vascular endothelial growth factor (VEGF-A) angiogenesis mediator and its FLT-1 and KDR receptors, and correlate with Doppler velocimetry of uterine artery and endometrial vascularization in bitches with CEH-pyometra syndrome. Bitches were allocated into CEH-mucometra Group (n = 13), Pyometra Group (n = 11), and Control Group (n = 8). Pyometra Group presented cytoplasmatic staining intensity for COX-2, VEGF-A, and FLT-1 and KDR receptors in luminal epithelium cells significantly higher compared to CEH-mucometra and Control groups. For the glandular epithelium, Pyometra Group had higher immunostaining score for VEGF-A and its receptors (FLT-1 and KDR). Hemodynamic indexes showed negative correlation with VEGF-A and its receptors as well as with COX-2. On the other hand, uterine vascularization score showed positive correlation in relation to immunostaining of COX-2, VEGF-A, and receptors in the endometrium luminal epithelium. In conclusion, uterus of bitches with CEH-pyometra syndrome show inflammatory process characterized by COX-2 expression, resulting in greater expression of proliferative Ki-67 marker as tissue response against the infectious agent. Furthermore, the increased VEGF-A expression and its receptors in CEH-pyometra reflect the increased blood flow and lower vascular resistance. Therefore, canine pyometra is characterized by an inflammatory, proliferative, and vascular disorder. © The Authors 2016. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

  12. Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

    PubMed Central

    Yi, Young-Su; Son, Young-Jin; Ryou, Chongsuk; Sung, Gi-Ho; Kim, Jong-Hoon; Cho, Jae Youl

    2014-01-01

    Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases. PMID:25045209

  13. Cellular and molecular regulation of innate inflammatory responses

    PubMed Central

    Liu, Juan; Cao, Xuetao

    2016-01-01

    Innate sensing of pathogens by pattern-recognition receptors (PRRs) plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inflammatory responses. The initiation, activation and resolution of innate inflammatory response are mediated by a complex network of interactions among the numerous cellular and molecular components of immune and non-immune system. While a controlled and beneficial innate inflammatory response is critical for the elimination of pathogens and maintenance of tissue homeostasis, dysregulated or sustained inflammation leads to pathological conditions such as chronic infection, inflammatory autoimmune diseases. In this review, we discuss some of the recent advances in our understanding of the cellular and molecular mechanisms for the establishment and regulation of innate immunity and inflammatory responses. PMID:27818489

  14. Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis

    PubMed Central

    Li, Ruidong; Wang, Yaxin; Ma, Zhijun; Ma, Muyuan; Wang, Di; Xie, Gengchen; Yin, Yuping

    2016-01-01

    Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS). Maresin 1 (Mar1) is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP) with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS) and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cre), and blood urea nitrogen (BUN) in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb) pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation. PMID:28042205

  15. Inflammatory myopathy in a patient with Aicardi-Goutières syndrome.

    PubMed

    Tumienė, Birutė; Voisin, Norine; Preikšaitienė, Eglė; Petroška, Donatas; Grikinienė, Jurgita; Samaitienė, Rūta; Utkus, Algirdas; Reymond, Alexandre; Kučinskas, Vaidutis

    2017-03-01

    Aicardi-Goutières syndrome (AGS) is an inflammatory disorder belonging to the recently characterized group of type I interferonopathies. The most consistently affected tissues in AGS are the central nervous system and skin, but various organ systems and tissues have been reported to be affected, pointing to the systemic nature of the disease. Here we describe a patient with AGS due to a homozygous p.Arg114His mutation in the TREX1 gene. The histologically proven inflammatory myopathy in our patient expands the range of clinical features of AGS. Histological signs of muscle biopsies in the proband, and in two other AGS patients described earlier, are similar to those seen in various autoimmune myositises and could be ascribed to inapproapriate IFN I activation. In view of signs of possible mitochondrial damage in AGS, we propose that mitochondrial DNA could be a trigger of autoimmune responses in AGS.

  16. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

    PubMed Central

    Silvestrin, Valentina; Bonvini, Stefano; Antonello, Michele; Grego, Franco; Vettor, Roberto

    2017-01-01

    After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid) for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid), the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol. PMID:28154580

  17. Platelet activation and apoptosis modulate monocyte inflammatory responses in dengue

    PubMed Central

    Hottz, Eugenio D.; Medeiros-de-Moraes, Isabel M.; Vieira-de-Abreu, Adriana; de Assis, Edson F.; Vals-de-Souza, Rogério; Castro-Faria-Neto, Hugo C.; Weyrich, Andrew S.; Zimmerman, Guy A.; Bozza, Fernando A.; Bozza, Patrícia T.

    2014-01-01

    Background Dengue is the most prevalent human arbovirus disease in the world. Dengue infection has a large spectrum of clinical manifestations from self-limited febrile illness to severe syndromes accompanied by bleeding and shock. Thrombocytopenia and vascular leak with altered cytokine profiles in plasma are features of severe dengue. Although monocytes have been recognized as important sources of cytokines in dengue, the contributions of platelet-monocyte interactions to inflammatory responses in dengue have not been addressed. Patients/Methods Patients with dengue were investigated for platelet-monocyte aggregate formation and markers of monocyte activation. Platelet-induced cytokine responses by monocytes and underlying mechanisms were also investigated in vitro. Results We observed increased levels of platelet-monocyte aggregates in blood samples from patients with dengue, especially patients with thrombocytopenia and increased vascular permeability. Moreover, the exposure of monocytes from healthy volunteers to platelets from patients with dengue induced the secretion of the cytokines IL-1β, IL-8, IL-10 and MCP-1, while the exposure to platelets from healthy volunteers only induced the secretion of MCP-1. In addition to the well-established modulation of monocyte cytokine responses by activated platelets through P-selectin binding, we found that interaction of monocytes with apoptotic platelets mediate IL-10 secretion through phosphatidylserine recognition in platelet-monocyte aggregates. Moreover, IL-10 secretion required platelet-monocyte contact but not phagocytosis. Conclusions Together, our results demonstrate that activated and apoptotic platelets aggregate with monocytes during dengue infection and signal specific cytokine responses that may contribute to the pathogenesis of dengue. PMID:25015827

  18. Rhodoccocus Equi Pneumonia and Paradoxical Immune Reconstitution Inflammatory Syndrome in a Patient with Acquired Immune Deficiency Syndrome (AIDS)

    PubMed Central

    Zijoo, Ritika; Dirweesh, Ahmed; Karabulut, Nigahus

    2017-01-01

    Patient: Male, 47 Final Diagnosis: Rhodococcus equi pneumonia • paradoxical immune reconstitution inflammatory syndrome Symptoms: Cough • fever • shorthness of breath Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare co-existance of disease or pathology Background: Pulmonary infections are a major cause of mortality and morbidity in patients infected with human immunodeficiency virus (HIV) and can progress rapidly to respiratory failure and death without appropriate therapy. Herein, we present a rare case of an advanced HIV infection and Rhodoccocus equi (R. equi) pneumonia in a young male who had severe paradoxical immune reconstitution inflammatory syndrome (IRIS). Case Report: A 47-year-old nonsmoking Hispanic man with advanced HIV infection presented with severe acute necrotizing pneumonia secondary to R. equi. Although his initial response to antimicrobial therapy was optimal, he became symptomatic again in spite of continuation of antibiotics as he developed severe paradoxical IRIS 3 weeks after starting a new highly active anti-retroviral therapy (HAART). Conclusions: The diagnosis of IRIS remains challenging because of the wide variations in the clinical presentation and etiologies. In spite of its rarity as an opportunistic pathogen, we recommend that R. equi, an intracellular pathogen, be included in the differential list of pathogens associated with IRIS. PMID:28100903

  19. Effect of Dietary Lipids on Endotoxemia Influences Postprandial Inflammatory Response.

    PubMed

    López-Moreno, Javier; García-Carpintero, Sonia; Jimenez-Lucena, Rosa; Haro, Carmen; Rangel-Zúñiga, Oriol A; Blanco-Rojo, Ruth; Yubero-Serrano, Elena M; Tinahones, Francisco J; Delgado-Lista, Javier; Pérez-Martínez, Pablo; Roche, Helen M; López-Miranda, José; Camargo, Antonio

    2017-09-06

    Metabolic syndrome (MetS) results in postprandial metabolic alterations that predisposes one to a state of chronic low-grade inflammation and increased oxidative stress. We aimed to assess the effect of the consumption of the quantity and quality of dietary fat on fasting and postprandial plasma lipopolysaccharides (LPS). A subgroup of 75 subjects with metabolic syndrome was randomized to receive 1 of 4 diets: HSFA, rich in saturated fat; HMUFA, rich in monounsaturated fat; LFHCC n-3, low-fat, rich in complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids; LFHCC low-fat, rich in complex carbohydrate diet supplemented with placebo, for 12 weeks each. We administered a fat challenge reflecting the fatty acid composition of the diets at postintervention. We determined the plasma lipoproteins and glucose and gene expression in peripheral blood mononuclear cells (PBMC) and adipose tissue. LPS and LPS binding protein (LBP) plasma levels were determined by ELISA, at fasting and postprandial (4 h after a fat challenge) states. We observed a postprandial increase in LPS levels after the intake of the HSFA meal, whereas we did not find any postprandial changes after the intake of the other three diets. Moreover, we found a positive relationship between the LPS plasma levels and the gene expression of IkBa and MIF1 in PBMC. No statistically significant differences in the LBP plasma levels at fasting or postprandial states were observed. Our results suggest that the consumption of HSFA diet increases the intestinal absorption of LPS which, in turn, increases postprandial endotoxemia levels and the postprandial inflammatory response.

  20. Autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA)--animal models as a proof of concept.

    PubMed

    Cruz-Tapias, Paola; Agmon-Levin, Nancy; Israeli, Eitan; Anaya, Juan-Manuel; Shoenfeld, Yehuda

    2013-01-01

    ASIA syndrome, "Autoimmune (Auto-inflammatory) Syndromes Induced by Adjuvants" includes at least four conditions which share a similar complex of signs and symptoms and have been defined by hyperactive immune responses: siliconosis, macrophagic myofasciitis syndrome, Gulf war syndrome and post-vaccination phenomena. Exposure to adjuvants has been documented in these four medical conditions, suggesting that the common denominator to these syndromes is a trigger entailing adjuvant activity. An important role of animal models in proving the ASIA concept has been established. Experimentally animal models of autoimmune diseases induced by adjuvants are currently widely used to understand the mechanisms and etiology and pathogenesis of these diseases and might thus promote the development of new diagnostic, predictive and therapeutic methods. In the current review we wish to unveil the variety of ASIA animal models associated with systemic and organ specific autoimmune diseases induced by adjuvants. We included in this review animal models for rheumatoid arthritis-like disease, for systemic lupus erythematosus-like disease, autoimmune thyroid disease-like disease, antiphospholipid syndrome, myocarditis and others. All these models support the concept of ASIA, as the Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants.

  1. Pathophysiology of the systemic inflammatory response after major accidental trauma.

    PubMed

    Brøchner, Anne Craveiro; Toft, Palle

    2009-09-15

    The purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. An unsystematic review of the medical literature was performed and articles pertaining to the inflammatory response to trauma were obtained. The literature selected was based on the preference and clinical expertise of authors. The inflammatory response consists of hormonal metabolic and immunological components and the extent correlates with the magnitude of the tissue injury. After trauma and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed. Trauma patients are, however, often exposed, not only to the trauma, but to several events in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated with increased risk of infection might develop. The inflammatory response is normalized 3 weeks following trauma. It has been proposed that the final reconstructive surgery should be postponed until the inflammatory response is normalized. This statement is however not based on clinical trials. Postponement of final reconstructive surgery until the inflammatory is normalized should be based on prospective randomized trials.

  2. Pathophysiology of the systemic inflammatory response after major accidental trauma

    PubMed Central

    2009-01-01

    Background The purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. Methods An unsystematic review of the medical literature was performed and articles pertaining to the inflammatory response to trauma were obtained. The literature selected was based on the preference and clinical expertise of authors. Discussion The inflammatory response consists of hormonal metabolic and immunological components and the extent correlates with the magnitude of the tissue injury. After trauma and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed. Trauma patients are, however, often exposed, not only to the trauma, but to several events in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated with increased risk of infection might develop. The inflammatory response is normalized 3 weeks following trauma. It has been proposed that the final reconstructive surgery should be postponed until the inflammatory response is normalized. This statement is however not based on clinical trials. Conclusion Postponement of final reconstructive surgery until the inflammatory is normalized should be based on prospective randomized trials. PMID:19754938

  3. A surprising role for uric acid: the inflammatory malaria response.

    PubMed

    Gallego-Delgado, Julio; Ty, Maureen; Orengo, Jamie M; van de Hoef, Diana; Rodriguez, Ana

    2014-02-01

    Malaria, which is caused by Plasmodium parasite erythrocyte infection, is a highly inflammatory disease with characteristic periodic fevers caused by the synchronous rupture of infected erythrocytes to release daughter parasites. Despite the importance of inflammation in the pathology and mortality induced by malaria, the parasite-derived factors inducing the inflammatory response are still not well characterized. Uric acid is emerging as a central inflammatory molecule in malaria. Not only is uric acid found in the precipitated form in infected erythrocytes, but high concentrations of hypoxanthine, a precursor for uric acid, also accumulate in infected erythrocytes. Both are released upon infected erythrocyte rupture into the circulation where hypoxanthine would be converted into uric acid and precipitated uric acid would encounter immune cells. Uric acid is an important contributor to inflammatory cytokine secretion, dendritic cell and T cell responses induced by Plasmodium, suggesting uric acid as a novel molecular target for anti-inflammatory therapies in malaria.

  4. Extracellular cyclophilins contribute to the regulation of inflammatory responses.

    PubMed

    Arora, Kamalpreet; Gwinn, William M; Bower, Molly A; Watson, Alan; Okwumabua, Ifeanyi; MacDonald, H Robson; Bukrinsky, Michael I; Constant, Stephanie L

    2005-07-01

    The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases.

  5. Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury

    PubMed Central

    Zhang, Qin; Raoof, Mustafa; Chen, Yu; Sumi, Yuka; Sursal, Tolga; Junger, Wolfgang; Brohi, Karim; Itagaki, Kiyoshi; Hauser, Carl J.

    2009-01-01

    Injury causes a systemic inflammatory response syndrome (SIRS) clinically much like sepsis 1. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors 2. Similarly, cellular injury can release endogenous damage-associated molecular patterns (DAMPs) that activate innate immunity 3. Mitochondria are evolutionary endosymbionts that were derived from bacteria 4 and so might bear bacterial molecular motifs. We show here that injury releases mitochondrial DAMPs (MTD) into the circulation with functionally important immune consequences. MTD include formyl peptides and mitochondrial DNA. These activate human neutrophils (PMN) through formyl peptide receptor-1 and TLR9 respectively. MTD promote PMN Ca2+ flux and phosphorylation of MAP kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTD can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These can then signal through identical innate immune pathways to create a sepsis-like state. The release of such mitochondrial ‘enemies within’ by cellular injury is a key link between trauma, inflammation and SIRS. PMID:20203610

  6. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes.

    PubMed

    Karussis, Dimitrios; Petrou, Panayiota

    2014-03-01

    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  7. Parkinson’s disease and enhanced inflammatory response

    PubMed Central

    Stojkovska, Iva; Wagner, Brandon M

    2015-01-01

    Parkinson’s disease (PD) is the first and second most prevalent motor and neurodegenerative disease, respectively. The clinical symptoms of PD result from a loss of midbrain dopaminergic (DA) neurons. However, the molecular cause of DA neuron loss remains elusive. Mounting evidence implicates enhanced inflammatory response in the development and progression of PD pathology. This review examines current research connecting PD and inflammatory response. PMID:25769314

  8. Immunopathology of immune reconstitution inflammatory syndrome in Whipple's disease.

    PubMed

    Moos, Verena; Feurle, Gerhard E; Schinnerling, Katina; Geelhaar, Anika; Friebel, Julian; Allers, Kristina; Moter, Annette; Kikhney, Judith; Loddenkemper, Christoph; Kühl, Anja A; Erben, Ulrike; Fenollar, Florence; Raoult, Didier; Schneider, Thomas

    2013-03-01

    During antimicrobial treatment of classic Whipple's disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4(+) T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3(+), predominantly CD45RO(+)CD4(+) T cells. In the periphery, initial reduction of CD4(+) cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4(+) T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4(+) T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei-specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4(+) T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.

  9. Inflammatory bowel disease and irritable bowel syndrome: similarities and differences.

    PubMed

    Barbara, Giovanni; Cremon, Cesare; Stanghellini, Vincenzo

    2014-07-01

    Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are classically viewed as dichotomous conditions. The former is perceived as a typical organic disease, and the latter is regarded as a disorder of gut function driven by mood. Recent research identified some shared contributing factors, which will be discussed here. Mounting evidence shows the importance in both IBD and IBS of genetic, microbiological, epithelial, and immunological factors. In some instances, these factors overlap in the two conditions as shown by: involvement of brain-gut axis dysfunction in IBD, implication of TNFSF gene in Crohn's disease and IBS, evidence of abnormal microbiota and its impact on host functions, identification of low-grade inflammation in subsets of IBS patients, and development of IBS symptoms in patients with IBD in remission. IBD and IBS remain separate conditions although there are some overlapping mechanisms. Both research and clinical management would benefit from considering a functional approach for certain manifestations of IBD and accepting an organic view in subsets of IBS patients.

  10. Inflammatory and Antioxidant Pattern Unbalance in “Clopidogrel-Resistant” Patients during Acute Coronary Syndrome

    PubMed Central

    Gori, Anna Maria; Cecchettini, Antonella; Parodi, Guido; Marcucci, Rossella; Parolini, Marina; Romagnuolo, Ilaria; Citti, Lorenzo; Abbate, Rosanna

    2015-01-01

    Background. In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel. Material and Methods. Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined. Results. Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased. Conclusions. In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness. PMID:25873769

  11. The inflammatory response to miniaturised extracorporeal circulation: a review of the literature.

    PubMed

    Vohra, Hunaid A; Whistance, Robert; Modi, Amit; Ohri, Sunil K

    2009-01-01

    Conventional cardiopulmonary bypass can trigger a systemic inflammatory response syndrome similar to sepsis. Aetiological factors include surgical trauma, reperfusion injury, and, most importantly, contact of the blood with the synthetic surfaces of the heart-lung machine. Recently, a new cardiopulmonary bypass system, mini-extracorporeal circulation (MECC), has been developed and has shown promising early results in terms of reducing this inflammatory response. It has no venous reservoir, a reduced priming volume, and less blood-synthetic interface. This review focuses on the inflammatory and clinical outcomes of using MECC and compares these to conventional cardio-pulmonary bypass (CCPB). MECC has been shown to reduce postoperative cytokines levels and other markers of inflammation. In addition, MECC reduces organ damage, postoperative complications and the need for blood transfusion. MECC is a safe and viable perfusion option and in certain circumstances it is superior to CCPB.

  12. Fetal inflammatory response and brain injury in the preterm newborn.

    PubMed

    Malaeb, Shadi; Dammann, Olaf

    2009-09-01

    Preterm birth can be caused by intrauterine infection and maternal/fetal inflammatory responses. Maternal inflammation (chorioamnionitis) is often followed by a systemic fetal inflammatory response characterized by elevated levels of proinflammatory cytokines in the fetal circulation. The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response. Microglial activation has a central role in this process and triggers excitotoxic, inflammatory, and oxidative damage in the developing brain. Neuroinflammation can persist over a period of time and sensitize the brain to subinjurious insults in early and chronic phases but may offer relative tolerance in the intermediate period through activation of endogenous anti-inflammatory, protective, and repair mechanisms. Neuroinflammatory injury not only destroys what exists but also changes what develops.

  13. Inflammatory response to trauma: Implications for coagulation and resuscitation

    PubMed Central

    Pierce, Albert; Pittet, Jean-François

    2014-01-01

    Purpose of this review Recent studies have changed our understanding of the timing and interactions of the inflammatory processes and coagulation cascade following severe trauma. This review highlights this information and correlates its impact on the current clinical approach for fluid resuscitation and treatment of coagulopathy for trauma patients. Recent findings Severe trauma is associated with a failure of multiple biologic emergency response systems that includes imbalanced inflammatory response, acute coagulopathy of trauma (ACOT), and endovascular glycocalyx degradation with microcirculatory compromise. These abnormalities are all inter-linked and related. Recent observations show that after severe trauma: 1) pro-inflammatory and anti-inflammatory responses are concomitant, not sequential and 2) resolution of the inflammatory response is an active process, not a passive one. Understanding these interrelated processes is considered extremely important for the development of future therapies for severe trauma in humans. Summary Traumatic injuries continue to be a significant cause of mortality worldwide. Recent advances in understanding the mechanisms of end-organ failure, and modulation of the inflammatory response has important clinical implications regarding fluid resuscitation and treatment of coagulopathy. PMID:24419158

  14. [Effect of anti-inflammatory therapy on the treatment of dry eye syndrome].

    PubMed

    Mrukwa-Kominek, Ewa; Rogowska-Godela, Anna; Gierek-Ciaciura, Stanisława

    2007-01-01

    Dry eye syndrome is a common chronic disease; agents and strategies for its effective management are still lacking. The syndrome tends to be accompanied by ocular surface inflammation; therefore, the use of anti-inflammatory agents might prove beneficial. The authors present up-to-date guidelines, strategies, and efficacy of dry eye syndrome management, including anti-inflammatory treatment. As no diagnostic tests are now available to assess ocular surface inflammation severity, the right timing to launch an anti-inflammatory agent is difficult to determine. Patients with mild intermittent bouts of symptoms which can be alleviated with ophthalmic lubricants do not typically require anti-inflammatory therapy. The latter should be considered in those who do not respond to lubricating drops, obtain poor results on clinical tests, and show symptoms of ocular surface irritation (eg. conjunctivae redness). Anti-inflammatory treatment of dry eye syndrome may include short-term corticosteroids, cyclosporine A emulsion, oral tetracycline therapy, oral omega-3 fatty acid supplements, and autologous serum eye drops. Anti-inflammatory treatment should be safe and effective; potential benefits should be evaluated for each individual patient. The authors have reviewed the advantages of anti-inflammatory treatment in dry eye syndrome, presented in literature.

  15. Senescence-associated inflammatory responses: aging and cancer perspectives.

    PubMed

    Lasry, Audrey; Ben-Neriah, Yinon

    2015-04-01

    Senescent cells, albeit not proliferating, are metabolically and transcriptionally active, thereby capable of affecting their microenvironment, notably via the production of inflammatory mediators. These mediators maintain and propagate the senescence process to neighboring cells, and then recruit immune cells for clearing senescent cells. Among the inflammatory cues are molecules with pronounced tumor-controlling properties, both growth and invasion factors and inhibitory factors, working directly or via recruited immune cells. These senescence-inflammatory effects also prevail within tumors, mediated by the senescent tumor cells and the senescent tumor stroma. Here, we review the course and impact of senescence-associated inflammatory responses in aging and cancer. We propose that controlling senescence-associated inflammation by targeting specific inflammatory mediators may have a beneficial therapeutic effect in treatment of cancer and aging-related diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Immune Reconstitution Inflammatory Syndrome Occurring in a Kidney Transplant Patient with Extrapulmonary Tuberculosis

    PubMed Central

    Ledesma, Kandria Jumil; Liu, Jessie

    2017-01-01

    Tuberculosis (TB) occurring in solid organ transplantation (SOT) is associated with significant morbidity and mortality usually due to delays in diagnosis, drug toxicity encountered with antimycobacterial therapy, and drug-drug interactions. TB in SOT patients may mimic other infectious and noninfectious posttransplant complications such as posttransplant lymphoproliferative disorder (PTLD) and systemic cytomegalovirus infection. Immune reconstitution inflammatory syndrome (IRIS) is a host response resulting in paradoxical worsening of an infectious disease which occurs after the employment of effective therapy and reversal of an immunosuppressed state. We describe the development of immune reconstitution inflammatory syndrome (IRIS), a unique complication occurring during the treatment of extrapulmonary tuberculosis occurring after transplant which resulted from decreasing immunosuppression in a patient who received Alemtuzumab induction therapy. Although (IRIS) has been originally described in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART), solid organ transplant recipients with diagnosed or occult TB whose immune system may undergo immune reconstitution during their posttransplant course represent a new high risk group. PMID:28367350

  17. Immune Reconstitution Inflammatory Syndrome Occurring in a Kidney Transplant Patient with Extrapulmonary Tuberculosis.

    PubMed

    Iglesias, Jose; Ledesma, Kandria Jumil; Couto, Paul J; Liu, Jessie

    2017-01-01

    Tuberculosis (TB) occurring in solid organ transplantation (SOT) is associated with significant morbidity and mortality usually due to delays in diagnosis, drug toxicity encountered with antimycobacterial therapy, and drug-drug interactions. TB in SOT patients may mimic other infectious and noninfectious posttransplant complications such as posttransplant lymphoproliferative disorder (PTLD) and systemic cytomegalovirus infection. Immune reconstitution inflammatory syndrome (IRIS) is a host response resulting in paradoxical worsening of an infectious disease which occurs after the employment of effective therapy and reversal of an immunosuppressed state. We describe the development of immune reconstitution inflammatory syndrome (IRIS), a unique complication occurring during the treatment of extrapulmonary tuberculosis occurring after transplant which resulted from decreasing immunosuppression in a patient who received Alemtuzumab induction therapy. Although (IRIS) has been originally described in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART), solid organ transplant recipients with diagnosed or occult TB whose immune system may undergo immune reconstitution during their posttransplant course represent a new high risk group.

  18. Common links between metabolic syndrome and inflammatory bowel disease: Current overview and future perspectives.

    PubMed

    Michalak, Arkadiusz; Mosińska, Paula; Fichna, Jakub

    2016-08-01

    Metabolic syndrome (MS) features a constellation of central obesity, dyslipidemia, impaired glucose metabolism and often hypertension joined by insulin resistance and chronic inflammation. All these elements greatly raise patient's risk of cardiovascular disease and type 2 diabetes, resulting in an increased mortality. Metabolic syndrome affects approximately 20-25% of the world's adult population and thus it is essential to study its pathophysiology and seek new pharmacological targets. There is a thoroughly studied link between MS and inflammatory diseases of the gastrointestinal (GI) system, i.e. steatohepatitis. However, recent findings also indicate similarities in pathophysiological features between MS and inflammatory bowel disease (IBD), including adipose tissue dysregulation, inadequate immune response, and inflammation. In this review we aim to outline the pathophysiology of MS and emphasize the aspects revealed recently, such as mineralocorticoid activity, involvement of sex hormones and an accompanying increase in prolactin secretion. More importantly, we focus on the common links between MS and IBD. Finally, we describe new strategies and drug targets that may be utilized in MS therapy, namely adiponectin mimetics, GLP-1-based multi agonists, ABCA1 agonists and possible role of miRNA. We also discuss the possible utility of selected agents as adjuvants in IBD therapy.

  19. Increased levels of inflammatory plasma markers and obesity risk in a mouse model of Down syndrome.

    PubMed

    Fructuoso, M; Rachdi, L; Philippe, E; Denis, R G; Magnan, C; Le Stunff, H; Janel, N; Dierssen, M

    2017-09-25

    Down syndrome (DS) is caused by the trisomy of human chromosome 21 and is the most common genetic cause of intellectual disability. In addition to the intellectual deficiencies and physical anomalies, DS individuals present a higher prevalence of obesity and subsequent metabolic disorders than healthy adults. There is increasing evidence from both clinical and experimental studies indicating the association of visceral obesity with a pro-inflammatory status and recent studies have reported that obese people with DS suffer from low-grade systemic inflammation. However, the link between adiposity and inflammation has not been explored in DS. Here we used Ts65Dn mice, a validated DS mouse model, for the study of obesity-related inflammatory markers. Ts65Dn mice presented increased energy intake, and a positive energy balance leading to increased adiposity (fat mass per body weight), but did not show overweight, which only was apparent upon high fat diet induced obesity. Trisomic mice also had fasting hyperglycemia and hypoinsulinemia, and normal incretin levels. Those trisomy-associated changes were accompanied by reduced ghrelin plasma levels and slightly but not significantly increased leptin levels. Upon a glucose load, Ts65Dn mice showed normal increase of incretins accompanied by over-responses of leptin and resistin, while maintaining the hyperglycemic and hypoinsulinemic phenotype. These changes in the adipoinsular axis were accompanied by increased plasma levels of inflammatory biomarkers previously correlated with obesity galectin-3 and HSP72, and reduced IL-6. Taken together, these results suggest that increased adiposity, and pro-inflammatory adipokines leading to low-grade inflammation are important players in the propensity to obesity in DS. We conclude that DS would be a case of impaired metabolic-inflammatory axis. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Carvacrol attenuates mechanical hypernociception and inflammatory response.

    PubMed

    Guimarães, Adriana G; Xavier, Maria A; de Santana, Marília T; Camargo, Enilton A; Santos, Cliomar A; Brito, Fabíola A; Barreto, Emiliano O; Cavalcanti, Sócrates C H; Antoniolli, Angelo R; Oliveira, Rita C M; Quintans-Júnior, Lucindo J

    2012-03-01

    Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 μg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

  1. Managing Sjögren’s Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy

    PubMed Central

    Coursey, Terry G; de Paiva, Cintia S

    2014-01-01

    Dry eye from Sjögren’s syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti–inflammatory therapies used to control this disease. PMID:25120351

  2. Translation Control: A Multifaceted Regulator of Inflammatory Response

    PubMed Central

    Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen

    2010-01-01

    A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxicshock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation. PMID:20304832

  3. Potential inflammatory markers in obstructive sleep apnea-hypopnea syndrome

    PubMed Central

    Lu, Dongmei; Li, Nanfang; Yao, Xiaoguang; Zhou, Ling

    2017-01-01

    Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a complex chronic inflammatory respiratory disease with multiple pathogenic factors and high morbidity and mortality. Serum levels of nuclear factor-κB (NF-κB), hypoxia-inducible factor-1 alpha (HIF-1α), and surfactant protein D (SPD) were investigated in OSAHS patients, to determine their clinical significance and correlation with the pathogenesis. Patients were classified into a mild and moderate OSAHS group (n = 25) and severe OSAHS group (n = 33). Twenty healthy patients served as a control group. Peripheral blood levels of NF-κB, HIF-1α, and SPD were determined by Western blot, and a correlation analysis was performed. Severe OSAHS patients received nasal continuous positive airway pressure (nCPAP) therapy and were followed up after 2 months. NF-κB p65, HIF-1α, and SPD expression levels were determined after valid nCPAP therapy. NF-κB p65 and HIF-1α expression was significantly higher in severe OSAHS group than in the other two groups (p < 0.01), and was positively correlated with the apnea-hypopnea index (AHI) (r = 0.696, p < 0.001; r = 0.634, p < 0.001). SPD expression was significantly lower in severe OSAHS group than in the control group (p < 0.01) and mild and moderate OSAHS group (p < 0.01), and was negatively correlated with AHI (r = −0.569, p < 0.001). OSAHS pathogenesis was associated with changes in NF-κB, HIF-1α, and SPD protein expression levels. nCPAP therapy could improve the clinical characteristics of the patients, lower serum NF-κB and HIF-1α levels, and increase serum SPD levels. We conclude that OSAHS is related to the expression of NF-κB, HIF-1, and SPD. PMID:27754829

  4. Infectious Complications and Immune/Inflammatory Response in Cardiogenic Shock Patients: A Prospective Observational Study

    PubMed Central

    Parenica, Jiri; Jarkovsky, Jiri; Malaska, Jan; Mebazaa, Alexandre; Gottwaldova, Jana; Helanova, Katerina; Litzman, Jiri; Dastych, Milan; Tomandl, Josef; Spinar, Jindrich; Dostalova, Ludmila; Lokaj, Petr; Tomandlova, Marie; Pavkova, Monika Goldergova; Sevcik, Pavel; Legrand, Matthieu

    2017-01-01

    ABSTRACT Introduction: Patients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers. Methods: Eighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock. Results: Infection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875. Conclusion: The prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most

  5. miR-146a-mediated suppression of the inflammatory response in human adipocytes

    PubMed Central

    Roos, Julian; Enlund, Eveliina; Funcke, Jan-Bernd; Tews, Daniel; Holzmann, Karlheinz; Debatin, Klaus-Michael; Wabitsch, Martin; Fischer-Posovszky, Pamela

    2016-01-01

    The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis. Recently, microRNAs (miRNAs) were identified as important regulators of WAT functions. Herein, we cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes with macrophage-conditioned medium (MacCM) and performed an Affimetrix miRNA array to identify miRNAs differentially expressed under inflammatory conditions. We identified 24 miRNAs differentially expressed upon inflammation in human adipocytes and miR-146a was the most up-regulated miRNA species. In subcutaneous WAT, miR-146a was elevated in both human and murine obesity. Transfection of miR-146a mimics prevented the MacCM-induced inflammatory response in SGBS adipocytes as seen by reduced levels of IL-8 and MCP-1 mRNA and protein. We identified IRAK1 and TRAF6 as targets of miR-146a in human adipocytes and detected a reduced inflammation-induced activation of JNK and p38 upon miR-146a transfection. Taken together, we could show that miR-146a reduces the inflammatory response in human adipocytes. In a negative feedback loop miR-146a might contribute to the regulation of inflammatory processes in WAT and possibly prevent an overwhelming inflammatory response. PMID:27922090

  6. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

    NASA Astrophysics Data System (ADS)

    Borovikova, Lyudmila V.; Ivanova, Svetlana; Zhang, Minghuang; Yang, Huan; Botchkina, Galina I.; Watkins, Linda R.; Wang, Haichao; Abumrad, Naji; Eaton, John W.; Tracey, Kevin J.

    2000-05-01

    Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1β, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.

  7. Anti-Inflammatory Dietary Combo in Overweight and Obese Women with Polycystic Ovary Syndrome

    PubMed Central

    Salama, Amany Alsayed; Amine, Ezzat Khamis; Salem, Hesham Abd Elfattah; Abd El Fattah, Nesrin Kamal

    2015-01-01

    Background: Polycystic ovary syndrome (PCOS) is of clinical and public health importance, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive, metabolic, and psychological features. Aim: The study was to investigate the effect of anti-inflammatory dietary combo on metabolic, endocrine, inflammatory, and reproductive profiles in overweight and obese women with PCOS. Materials and Methods: A total of 100 nonpregnant, overweight, and obese adult females with PCOS according to the Rotterdam criteria, were screened during the year 2012, and 75 completed the trial. At baseline and study end, fasting blood samples were drawn to measure biological markers, body fat percent (BFP), and visceral fat area (VFA) were assessed by the InBody720 device and anthropometric measurements were done for all participants who were subjected to an anti-inflammatory hypocaloric diet and physical activity for 12 weeks. Results: At study completion, we achieved moderate weight loss of (± 7%) and significant improvements in body composition, hormones and menstrual cyclicity, blood pressure, glucose homeostasis, dyslipidemia, C-reactive protein (CRP), and serum amyloid A (SAA) (surrogate measures of cardiovascular risk (CVR)). This was a clinically relevant weight loss that is associated with a reduced prevalence of type 2 diabetes mellitus (DM2) and metabolic syndrome (MS) in the general population and improved fertility outcomes in PCOS. We achieved 63% regain of menstrual cyclicity and 12% spontaneous pregnancy rate within 12 week. Conclusions: We have explored an additional dietary treatment option with good prognostic metabolic and reproductive responses to weight loss that occur in overweight and obese PCOS. PMID:26258078

  8. Impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, and quality of life.

    PubMed

    Schindlbeck, Katharina A; Becker, Janek; Berger, Felix; Mehl, Arne; Rewitzer, Charlotte; Geffe, Sarah; Koch, Peter M; Preiß, Jan C; Siegmund, Britta; Maul, Jochen; Marzinzik, Frank

    2017-01-01

    Inflammatory bowel disease has been associated with neurological symptoms including restless legs syndrome. Here, we investigated the impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, mood, cognition, and quality of life. Two groups of inflammatory bowel disease patients, with and without restless legs syndrome, were prospectively evaluated for sleep disorders, fatigue, daytime sleepiness, depression, anxiety, and health-related quality of life. Furthermore, global cognitive function, executive function, attention, and concentration were assessed in both groups. Disease activity and duration of inflammatory bowel disease as well as current medication were assessed by interview. Inflammatory bowel disease patients with and without restless legs syndrome were matched for age, education, severity, and duration of their inflammatory bowel disease. Patients with inflammatory bowel disease and clinically relevant restless leg syndrome suffered significantly more frequent from sleep disturbances including sleep latency and duration, more fatigue, and worse health-related quality of life as compared to inflammatory bowel disease patients without restless legs syndrome. Affect and cognitive function including cognitive flexibility, attention, and concentration showed no significant differences among groups, indicating to be not related to restless legs syndrome. Sleep disorders including longer sleep latency, shorter sleep duration, and fatigue are characteristic symptoms of restless legs syndrome in inflammatory bowel disease patients, resulting in worse health-related quality of life. Therefore, clinicians treating patients with inflammatory bowel disease should be alert for restless legs syndrome.

  9. Lung dendritic cells and the inflammatory response.

    PubMed

    Grayson, Mitchell H

    2006-05-01

    To discuss the role of conventional and plasmacytoid dendritic cells in inducing and modulating immune responses in the lung. The primary literature and selected review articles studying the role of dendritic cells in both rodent and human lungs as identified via a PubMed/MEDLINE search using the keywords dendritic cell, antigen-presenting cell, viral airway disease, asthma, allergy, and atopy. The author's knowledge of the field was used to identify studies that were relevant to the stated objective. Dendritic cells are well positioned in the respiratory tract and other mucosal surfaces to respond to any foreign protein. These cells are crucial to the initiation of the adaptive immune response through induction of antigen specific T-cell responses. These cells also play an important role in the regulation of developing and ongoing immune responses, an area that is currently under intense investigation. This review discusses the various subsets of human and rodent dendritic cells and the pathways involved in antigen processing and subsequent immune regulation by dendritic cells in the lung using both viral and nonviral allergenic protein exposure as examples. Conventional and plasmacytoid dendritic cells are uniquely situated in the immune cascade to not only initiate but also modulate immune responses. Therapeutic interventions in allergic and asthmatic diseases will likely be developed to take advantage of this exclusive position of the dendritic cell.

  10. Inflammatory responses to influenza vaccination at the extremes of age.

    PubMed

    McDonald, Jacqueline U; Zhong, Ziyun; Groves, Helen T; Tregoning, John S

    2017-08-01

    Age affects the immune response to vaccination, with individuals at the extremes of age responding poorly. The initial inflammatory response to antigenic materials shapes the subsequent adaptive response and so understanding is required about the effect of age on the profile of acute inflammatory mediators. In this study we measured the local and systemic inflammatory response after influenza vaccination or infection in neonatal, young adult and aged mice. Mice were immunized intramuscularly with inactivated influenza vaccine with and without the adjuvant MF59 and then challenged with H1N1 influenza. Age was the major factor affecting the inflammatory profile after vaccination: neonatal mice had more interleukin-1α (IL-1α), C-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GMCSF), young adults more tumour necrosis factor-α (TNF), and elderly mice more interleukin-1 receptor antagonist (IL-1RA), IL-2RA and interferon-γ-induced protein 10 (IP10). Notably the addition of MF59 induced IL-5, granulocyte colony-stimulating factor (G-CSF), Keratinocyte Chemotractant (KC) and monocyte chemoattractant protein 1 (MCP1) in all ages of animals and levels of these cytokines correlated with antibody responses. Age also had an impact on the efficacy of vaccination: neonatal and young adult mice were protected against challenge, but aged mice were not. There were striking differences in the localization of the cytokine response depending on the route of exposure: vaccination led to a high serum response whereas intranasal infection led to a low serum response but a high lung response. In conclusion, we demonstrate that age affects the inflammatory response to both influenza vaccination and infection. These age-induced differences need to be considered when developing vaccination strategies for different age groups. © 2017 John Wiley & Sons Ltd.

  11. Delayed Stress Response Syndrome: Family Therapy Indications

    ERIC Educational Resources Information Center

    Figley, Charles R.; Sprenkle, Douglas H.

    1978-01-01

    The delayed stress response syndrome is a form of chronic catastrophic stress disorder. The theoretical nature of the syndrome and its most characteristic symptoms are delineated within the context of treating Vietnam combat veterans. The paper outlines treatment implications within a family therapy program. (Author)

  12. Hydrodynamic Regulation of Monocyte Inflammatory Response to an Intracellular Pathogen

    PubMed Central

    Evani, Shankar J.; Murthy, Ashlesh K.; Mareedu, Naresh; Montgomery, Robbie K.; Arulanandam, Bernard P.; Ramasubramanian, Anand K.

    2011-01-01

    Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation. PMID:21249123

  13. Fibrin(ogen) mediates acute inflammatory responses to biomaterials

    PubMed Central

    1993-01-01

    Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma- coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation. PMID:8245787

  14. Saturated fatty acids trigger TLR4-mediated inflammatory response.

    PubMed

    Rocha, D M; Caldas, A P; Oliveira, L L; Bressan, J; Hermsdorff, H H

    2016-01-01

    Toll-like receptors (TLR) mediate infection-induced inflammation and sterile inflammation by endogenous molecules. Among the TLR family, TLR4 is the best understood. However, while its downstream signaling pathways have been well defined, not all ligands of TLR4 are currently known. Current evidence suggests that saturated fatty acids (SFA) act as non-microbial TLR4 agonists, and trigger its inflammatory response. Thus, our present review provides a new perspective on the potential mechanism by which SFAs could modulate TLR4-induced inflammatory responses: (1) SFAs can be recognized by CD14-TLR4-MD2 complex and trigger inflammatory pathways, similar to lipopolysaccharide (LPS). (2) SFAs lead to modification of gut microbiota with an overproduction of LPS after a high-fat intake, enhancing this natural TLR4 ligand. (3) In addition, this metabolic endotoxemia leads to an oxidative stress thereby producing atherogenic lipids - oxLDL and oxidized phospholipids - which trigger CD36-TLR4-TLR6 inflammatory response. (4) Also, the high SFA consumption increases the lipemia and the mmLDL and oxLDL formation through oxidative modifications of LDL. The mmLDL, unlike oxLDL, is involved in activation of the CD14-TLR4-MD2 inflammatory pathway. Those molecules can induce TLR4 inflammatory response by MyD88-dependent and/or MyD88-independent pathways that, in turn, promotes the expression of proinflammatory transcript factors such as factor nuclear kappa B (NF-κB), which plays a crucial role in the induction of inflammatory mediators (cytokines, chemokines, or costimulatory molecules) implicated in the development and progression of many chronic diseases.

  15. Suppression of inflammatory responses by labdane-type diterpenoids.

    PubMed

    Girón, Natalia; Través, Paqui G; Rodríguez, Benjamín; López-Fontal, Raquel; Boscá, Lisardo; Hortelano, Sonsoles; de las Heras, Beatriz

    2008-04-15

    A series of 11 labdane-type diterpenoids (1-11) with various patterns of substitution were tested for potential anti-inflammatory activity. Of these compounds, 4 and 11 were selected to evaluate their influence on targets relevant to the regulation of the inflammatory response. These diterpenoids reduced the production of nitric oxide (NO), prostaglandin E2, and tumor necrosis factor-alpha in LPS-activated RAW 264.7 macrophages, with IC50 in the range 1-10 microM. Inhibition of these inflammatory mediators was related to inhibition of the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) at the transcriptional level, as determined by western-blot and RT-PCR. Examination of the effects of these diterpenoids on nuclear factor kappaB signaling showed that both compounds inhibit the phosphorylation of IkappaBalpha and IkappaBbeta, preventing their degradation and the nuclear translocation of the NF-kappaB p65 subunit. Inhibition of IKK activity was also observed. These derivatives displayed significant anti-inflammatory activity in vivo, suppressing mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibiting myeloperoxidase activity, an index of neutrophil infiltration. The anti-inflammatory effects of these labdane diterpenoids, together with their low cell toxicity, suggest potential therapeutic applications in the regulation of the inflammatory response.

  16. Supression of inflammatory responses by labdane-type diterpenoids

    SciTech Connect

    Giron, Natalia; Rodriguez, Benjamin; Lopez-Fontal, Raquel; Bosca, Lisardo; Hortelano, Sonsoles Heras, Beatriz de las

    2008-04-15

    A series of 11 labdane-type diterpenoids (1-11) with various patterns of substitution were tested for potential anti-inflammatory activity. Of these compounds, 4 and 11 were selected to evaluate their influence on targets relevant to the regulation of the inflammatory response. These diterpenoids reduced the production of nitric oxide (NO), prostaglandin E2, and tumor necrosis factor-{alpha} in LPS-activated RAW 264.7 macrophages, with IC50 in the range 1-10 {mu}M. Inhibition of these inflammatory mediators was related to inhibition of the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) at the transcriptional level, as determined by western-blot and RT-PCR. Examination of the effects of these diterpenoids on nuclear factor {kappa}B signaling showed that both compounds inhibit the phosphorylation of I{kappa}B{alpha} and I{kappa}B{beta}, preventing their degradation and the nuclear translocation of the NF-{kappa}B p65 subunit. Inhibition of IKK activity was also observed. These derivatives displayed significant anti-inflammatory activity in vivo, suppressing mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibiting myeloperoxidase activity, an index of neutrophil infiltration. The anti-inflammatory effects of these labdane diterpenoids, together with their low cell toxicity, suggest potential therapeutic applications in the regulation of the inflammatory response.

  17. Exploring the Risk Factors for Sudden Infant Deaths and Their Role in Inflammatory Responses to Infection

    PubMed Central

    Blackwell, Caroline; Moscovis, Sophia; Hall, Sharron; Burns, Christine; Scott, Rodney J.

    2015-01-01

    The risk factors for sudden infant death syndrome (SIDS) parallel those associated with susceptibility to or severity of infectious diseases. There is no evidence that a single infectious agent is associated with SIDS; the common thread appears to be induction of inflammatory responses to infections. In this review, interactions between genetic and environmental risk factors for SIDS are assessed in relation to the hypothesis that many infant deaths result from dysregulation of inflammatory responses to “minor” infections. Risk factors are assessed in relation to three important stages of infection: (1) bacterial colonization (frequency or density); (2) induction of temperature-dependent toxins; (3) induction or control of inflammatory responses. In this article, we review the interactions among risk factors for SIDS for their effects on induction or control of inflammatory responses. The risk factors studied are genetic factors (sex, cytokine gene polymorphisms among ethnic groups at high or low risk of SIDS); developmental stage (changes in cortisol and testosterone levels associated with 2- to 4-month age range); environmental factors (virus infection, exposure to cigarette smoke). These interactions help to explain differences in the incidences of SIDS observed between ethnic groups prior to public health campaigns to reduce these infant deaths. PMID:25798137

  18. The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology.

    PubMed

    Millar, Jonathan E; Fanning, Jonathon P; McDonald, Charles I; McAuley, Daniel F; Fraser, John F

    2016-11-28

    Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient's blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.

  19. 20 Years On: Is It Time to Redefine the Systemic Inflammatory Response to Cardiothoracic Surgery?

    PubMed

    Landis, R Clive

    2015-03-01

    The "systemic inflammatory response" has never been defined from a cardiothoracic surgery perspective, but borrowed its definition from the critical care field at a landmark 1992 definition conference on sepsis. It is unclear why the diagnostic criteria for the Systemic Inflammatory Response Syndrome (SIRS) were adopted in isolation, ignoring other potentially more useful definitions for Severe Septic Shock or Secondary Multiple Organ Dysfunction Syndrome. The 1992 SIRS definition for sepsis has since been updated at a conference in 2001 advocating PIRO (Predisposition, Infection, host Response, Organ dysfunction) as a hypothetical model to better link sepsis with clinical outcome. PIRO is readily adaptable to cardiothoracic surgery and provides the precedent and road map for how to update a definition. The need is obvious since the current definition of SIRS is widely disregarded in heart surgery: a dwindling proportion (14%) of articles on the systemic inflammatory response even mention SIRS and 0% monitored SIRS criteria in the past decade in an evidence-based review of anti-inflammatory interventions. The name "inflammatory response" is also problematic; it is too narrow and might be replaced with host response (the R in PIRO) to better convey the wide spectrum of host defensive pathways activated during heart surgery (i.e., complement, coagulation, fibrinolysis, kinins, cytokines, proteases, hemolysis, oxidative stiess). A variant on PIRO could allow these elements of the host Response (R) to be anchored within the context of Premorbid conditions (P) and the inevitable Insult (I) from surgery, to better link risk exposures to Organ dysfunction (O) in heart surgery. The precedent of PIRO suggests the following steps will be required to redefine the systemic inflammatory response: 1) buy-in from the leading societies for cardiothoracic surgery, anesthesia, and perfusion on the need for a re-definition conference, 2) assigning relative risk scores to different

  20. Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions.

    PubMed

    Haddow, Lewis J; Colebunders, Robert; Meintjes, Graeme; Lawn, Stephen D; Elliott, Julian H; Manabe, Yukari C; Bohjanen, Paul R; Sungkanuparph, Somnuek; Easterbrook, Philippa J; French, Martyn A; Boulware, David R

    2010-11-01

    Cryptococcal immune reconstitution inflammatory syndrome (IRIS) may present as a clinical worsening or new presentation of cryptococcal disease after initiation of antiretroviral therapy (ART), and is thought to be caused by recovery of cryptococcus-specific immune responses. We have reviewed reports of cryptococcal IRIS and have developed a consensus case definition specifically for paradoxical crytopcoccal IRIS in patients with HIV-1 and known cryptococcal disease before ART, and a separate definition for incident cryptococcosis developed during ART (termed ART-associated cryptococcosis), for which a proportion of cases are likely to be unmasking cryptococcal IRIS. These structured case definitions are intended to aid design of future clinical, epidemiological, and immunopathological studies of cryptococcal IRIS, to standardise diagnostic criteria, and to facilitate comparisons between studies. As for definitions of tuberculosis-associated IRIS, definitions for cryptococcal IRIS should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement.

  1. Immune reconstitution inflammatory syndrome: incidence and implications for mortality.

    PubMed

    Novak, Richard M; Richardson, James T; Buchacz, Kate; Chmiel, Joan S; Durham, Marcus D; Palella, Frank J; Wendrow, Andrea; Wood, Kathy; Young, Benjamin; Brooks, John T

    2012-03-27

    To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition. We studied 2,610 patients seen during 1996-2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log(10) copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period. We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models. We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/μl, respectively; median viral load was 2.7 log(10) copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi's sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/μl vs. at least 200 cells/μl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log(10) copies vs. less than 4.0 log(10) copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality. In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality.

  2. Immune reconstitution inflammatory syndrome: incidence and implications for mortality

    PubMed Central

    Novak, Richard M.; Richardson, James T.; Buchacz, Kate; Chmiel, Joan S.; Durham, Marcus D.; Palella, Frank J.; Wendrow, Andrea; Wood, Kathy; Young, Benjamin; Brooks, John T.

    2015-01-01

    Objective To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition. Design We studied 2 610 patients seen during 1996–2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log10 copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period. Methods We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models. Results We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/μl, respectively; median viral load was 2.7 log10 copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi’s sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/μl vs. at least 200 cells/μl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log10 copies vs. less than 4.0 log10 copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality. Conclusion In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality. PMID:22233655

  3. Erythema elevatum diutinum in acquired immune deficiency syndrome: Can it be an immune reconstitution inflammatory syndrome?

    PubMed Central

    Jose, Sheethal K; Marfatia, Yogesh S.

    2016-01-01

    A 47-year-old male with acquired immune deficiency syndrome (AIDS) presented with multiple hyperpigmented papules and nodules on both ankles, dorsum of bilateral feet and soles. It was associated with mild itching and pain. The patient was diagnosed with human immunodeficiency virus (HIV) in 2007. First-line antiretroviral therapy (ART) was started in 2009 to which he responded initially. He was shifted to second-line ART 11 months ago in March 2015 due to treatment failure as suggested by CD4 count of 50 cells/mm3. The present skin lesions started 2 months after the initiation of second-line ART. Differential diagnoses considered were Kaposi's sarcoma and immune reconstitution inflammatory syndrome (IRIS) related infections, but biopsy was suggestive of erythema elevatum diutinum (EED). Patient was started on oral dapsone 100 mg/day and increased to 200 mg/day to which he is responding gradually. In the present case, appearance of the lesions after initiation of second-line ART coupled with increase in CD4 count and decrease of viral load below undetectable level suggest that EED could be an IRIS. PMID:27190420

  4. Pathophysiological changes of inflammatory syndrome in multiple sclerosis after instituting therapeutic plasmapheresis

    PubMed Central

    Vlaic, S; Poalelungi, V; Bălăeţ, M; Purcărea, VL; Bălăeţ, C; Coculescu, BI

    2017-01-01

    In autoimmune conditions affecting the central and peripheral CNS as well as in multiple sclerosis (MS), the inflammatory syndrome is present with the onset of this disease. The present paper aimed to highlight the inflammatory syndrome based on the leukergia test, the total blood viscosity test, blood filterability test as well as on other tests. The early instituting of the therapeutic plasmapheresis beneficially modified the clinical status, the biological and pathophysiological behavior of the patient’s illness. Objective of the paper: The aim was to highlight the importance, advantages, and pathophysiological changes after therapeutic plasmapheresis in five cases, in patients hospitalized with the diagnosis of multiple sclerosis. Material and method: In order to emphasize the inflammatory syndrome, the determination of leukergia assay, the total blood viscosity test and the blood filterability test were added to regular examinations, conducted on the batch of patients included in the study. Results and discussions: As a result of using therapeutic plasmapheresis, the inflammatory parameters in patients with multiple sclerosis improved beneficially as it was proven by the values of inflammatory tests before and after plasmapheresis. Conclusions: In the treatment of multiple sclerosis, plasmapheresis proved to be a medical method that significantly reduced autoimmune inflammatory “installed” syndrome. PMID:28255377

  5. Pathophysiological changes of inflammatory syndrome in multiple sclerosis after instituting therapeutic plasmapheresis.

    PubMed

    Vlaic, S; Poalelungi, V; Bălăeţ, M; Purcărea, V L; Bălăeţ, C; Coculescu, B I

    2017-01-01

    In autoimmune conditions affecting the central and peripheral CNS as well as in multiple sclerosis (MS), the inflammatory syndrome is present with the onset of this disease. The present paper aimed to highlight the inflammatory syndrome based on the leukergia test, the total blood viscosity test, blood filterability test as well as on other tests. The early instituting of the therapeutic plasmapheresis beneficially modified the clinical status, the biological and pathophysiological behavior of the patient's illness. Objective of the paper: The aim was to highlight the importance, advantages, and pathophysiological changes after therapeutic plasmapheresis in five cases, in patients hospitalized with the diagnosis of multiple sclerosis. Material and method: In order to emphasize the inflammatory syndrome, the determination of leukergia assay, the total blood viscosity test and the blood filterability test were added to regular examinations, conducted on the batch of patients included in the study. Results and discussions: As a result of using therapeutic plasmapheresis, the inflammatory parameters in patients with multiple sclerosis improved beneficially as it was proven by the values of inflammatory tests before and after plasmapheresis. Conclusions: In the treatment of multiple sclerosis, plasmapheresis proved to be a medical method that significantly reduced autoimmune inflammatory "installed" syndrome.

  6. Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.

    PubMed

    Poelkens, Fleur; Lammers, Gerwen; Pardoel, Elisabeth M; Tack, Cees J; Hopman, Maria T E

    2013-10-01

    The metabolic syndrome, a combination of interrelated metabolic risk factors, is associated with insulin resistance and promotes the development of cardiovascular diseases and type 2 diabetes mellitus. There is a close link between inflammation and metabolic disease, but the responsible mechanisms remain elusive. The aim of this study was to identify differentially expressed genes in insulin-resistant skeletal muscle tissue of women with the metabolic syndrome compared with healthy control women. Women with the metabolic syndrome (n = 19) and healthy control women (n = 20) were extensively phenotyped, insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp, and a skeletal muscle biopsy was obtained. Gene expression levels were compared between the two groups by microarrays. The upregulated genes in skeletal muscle of the women with the metabolic syndrome were primarily enriched for inflammatory response-associated genes. The three most significantly upregulated of this group, interleukin 6 receptor (IL6R), histone deacetylase 9 (HDAC9) and CD97 molecule (CD97), were significantly correlated with insulin resistance. Taken together, these findings suggest an important role for a number of inflammatory-related genes in the development of skeletal muscle insulin resistance.

  7. Topiramate responsive exploding head syndrome.

    PubMed

    Palikh, Gaurang M; Vaughn, Bradley V

    2010-08-15

    Exploding head syndrome is a rare phenomenon but can be a significant disruption to quality of life. We describe a 39-year-old female with symptoms of a loud bang and buzz at sleep onset for 3 years. EEG monitoring confirmed these events occurred in transition from stage 1 sleep. This patient reported improvement in intensity of events with topiramate medication. Based on these results, topiramate may be an alternative method to reduce the intensity of events in exploding head syndrome.

  8. The immune and inflammatory response to orf virus.

    PubMed

    Haig, D M; McInnes, C; Deane, D; Reid, H; Mercer, A

    1997-06-01

    Orf virus is a zoonotic, epitheliotropic DNA parapox virus that principally infects sheep and goats. The fact that the virus can repeatedly reinfect sheep has provoked an interest in the underlying cellular, virological and molecular mechanisms for its apparent escape from the host protective immune response. The local immune and inflammatory response in skin and the cell phenotype and cytokine response in lymph analysed around a single lymph node are characteristic of an anti-viral response. An unusual feature is the dense accumulation of MHC Class II+ dendritic cells in the skin lesion. The function of these cells is not known. Orf virus virulence genes and activities have been identified that may interfere with the development of the host protective immune and inflammatory response.

  9. Irritable bowel syndrome and active inflammatory bowel disease diagnosed by faecal gas analysis.

    PubMed

    Aggio, R B M; White, P; Jayasena, H; de Lacy Costello, B; Ratcliffe, N M; Probert, C S J

    2017-01-01

    Inflammatory bowel disease and irritable bowel syndrome may present in a similar manner. Measuring faecal calprotectin concentration is often recommended to rule out inflammatory bowel disease, however, there are no tests to positively diagnose irritable bowel syndrome and invasive tests are still used to rule out other pathologies. To investigate a platform technology for diagnosing inflammatory bowel disease and irritable bowel syndrome based on faecal gas. The platform technology is composed of a gas chromatography column coupled to a metal oxide gas sensor (OdoReader) and a computer algorithm. The OdoReader separates the volatile compounds from faecal gas and the computer algorithm identifies resistance patterns associated with specific medical conditions and builds classification models. This platform was applied to faecal samples from 152 patients: 33 patients with active inflammatory bowel disease; 50 patients with inactive inflammatory bowel disease; 28 patients with irritable bowel syndrome and 41 healthy donors (Control). The platform classified samples with accuracies from 75% to 100% using rigorous validation schemes: namely leave-one-out cross-validation, 10-fold cross-validation, double cross-validation and their Monte Carlo variations. The most clinically important findings, after double cross-validation, were the accuracy of active Crohn's disease vs. irritable bowel syndrome (87%; CI 84-89%) and irritable bowel syndrome vs. controls (78%; CI 76-80%). These schemes provide an estimate of out-of-sample predictive accuracy for similar populations. This is the first description of an investigation for the positive diagnosis of irritable bowel syndrome, and for diagnosing inflammatory bowel disease. © 2016 John Wiley & Sons Ltd.

  10. Genomic responses in mouse models poorly mimic human inflammatory diseases.

    PubMed

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

  11. Genomic responses in mouse models poorly mimic human inflammatory diseases

    PubMed Central

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  12. Synergistic effects of anethole and ibuprofen in acute inflammatory response.

    PubMed

    Wisniewski-Rebecca, Edirlene S; Rocha, Bruno A; Wiirzler, Luiz A M; Cuman, Roberto K N; Velazquez-Martinez, Carlos A; Bersani-Amado, Ciomar A

    2015-12-05

    This study assessed the effect of the combination of anethole and ibuprofen in comparison with monotherapy by either drug alone, using two in vivo inflammatory models, namely the pleurisy and paw edema in rats. We also measured the levels of the TNF protein in plasma, and the ability of anethole to inhibit, in vitro, the activity of the cyclooxygenase 1 and cyclooxygenase 2 enzymes. The test drugs (anethole; ibuprofen; anethole + ibuprofen), at different doses, were administered once (p.o.) 60 min before the induction of the inflammatory response. The association of anethole + ibuprofen inhibited the development of the inflammatory response in both models used. This effect can be partially explained by the inhibitory action on the production of TNF and of COX isoforms. The isobologram analysis evidenced a synergistic effect between ibuprofen and anethole, because the combination of drugs showed a higher inhibitory potential than either drug alone.

  13. Syk-Mediated Suppression of Inflammatory Responses by Cordyceps bassiana.

    PubMed

    Yang, Woo Seok; Nam, Gyeong Sug; Kim, Mi-Yeon; Cho, Jae Youl

    2017-01-01

    The fruit body of artificially cultivated Cordyceps bassiana has been reported to exhibit anti-inflammatory and anticancer activities. Although it has been suggested that the fruit body has neutraceutic and pharmaceutic biomaterial potential, the exact anti-inflammatory molecular mechanism has not been fully elucidated. In this study, we demonstrated the immunopharmacologic activity of Cordyceps bassiana under in vitro conditions and investigated its anti-inflammatory mechanism. Water extract (Cm-WE) of the fruit body of artificially cultivated Cordyceps bassiana without polysaccharide fractions reduced the expression of the proinflammatory genes cyclooxygenase (COX)-2, interleukin (IL)-12, and inducible nitric oxide synthase (iNOS) and promoted the expression of the anti-inflammatory gene IL-10 in lipopolysaccharide (LPS)-treated RAW264.7 cells. In addition, this fraction suppressed proliferation and interferon (IFN)-[Formula: see text] production in splenic T lymphocytes. Cm-WE blocked the activation of nuclear factor (NF)-[Formula: see text]B and activator protein (AP)-1 and their upstream inflammatory signaling cascades, including Syk, MEK, and JNK. Using kinase assays, Syk was identified as the target enzyme most strongly inhibited by Cm-WE. These results strongly suggest that Cm-WE suppresses inflammatory responses by inhibiting Syk kinase activity, with potential implications for novel neutraceutic and pharmaceutic biomaterials.

  14. The systemic inflammatory response following femoral canal reaming using the reamer-irrigator-aspirator (RIA) device.

    PubMed

    Giannoudis, P V; Tan, H B; Perry, S; Tzioupis, C; Kanakaris, N K

    2010-11-01

    We evaluated the peripheral release of inflammatory mediators after femoral fracture and subsequent intramedullary reaming using the RIA reamers. IL-6 was elevated after trauma, and reaming with RIA induced a measurable second hit response. However, despite a higher ISS, the levels of IL-6 in the RIA group were similar to the levels measured in a group of patients where reaming of the femoral canal was performed using conventional reamers. There was one death related to fat embolism syndrome in the conventional reamers group. However, the overall incidence of complications was low and similar between the 2 groups of studied patients. In polytrauma patients, large scale studies are desirable to evaluate further the immuno-inflammatory response using the RIA reamers prior to the instrumentation of the femoral canal.

  15. Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome.

    PubMed

    Goodman, R B; Strieter, R M; Martin, D P; Steinberg, K P; Milberg, J A; Maunder, R J; Kunkel, S L; Walz, A; Hudson, L D; Martin, T R

    1996-09-01

    To determine the relationship between airspace cytokines and cellular inflammatory responses in patients with the acute respiratory distress syndrome (ARDS), we performed bronchoalveolar lavage (BAL) in 82 prospectively identified, mechanically ventilated patients on Days 3, 7, 14, and/or 21 after the onset of ARDS. We studied the relationships between bronchoalveolar lavage fluid (BALF) cell populations and the concentrations of two potent neutrophil (PMN) chemoattractants, interleukin-8 (IL-8) and epithelial cell-derived neutrophil activator-78 (ENA-78); two potent monocyte chemoattractants, monocyte chemotactic peptide-1 (MCP-1) and macrophage inflammatory peptide-1 alpha (MIP-1 alpha); and the early response cytokine interleukin-1 beta (IL-1 beta) and its naturally occurring antagonist, IL-1 receptor antagonist protein (IRAP). We found that all of these cytokines were significantly increased regardless of the duration of ARDS. IL-8 and ENA-78 were the cytokines most strongly and consistently correlated with PMN concentrations in the lung fluids of patients with ARDS, and the correlations were independent of the other cytokines or coexisting lung infection. None of the cytokines tested correlated with macrophage concentrations. MCP-1 was directly correlated with lung injury score on Days 7, 14, and 21. Although neither IL-8 nor ENA-78 was associated with outcome, levels of IL-1 beta measured on Day 7 were associated with an increased risk of death (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.1 to 7.4). These data demonstrate potential molecular mechanisms of the persistent inflammatory process in the lungs of patients with ARDS.

  16. The sick building syndrome as a part of the autoimmune (auto-inflammatory) syndrome induced by adjuvants.

    PubMed

    Israeli, Eitan; Pardo, Asher

    2011-06-01

    Sick building syndrome (SBS) is a term coined for a set of clinically recognizable symptoms and ailments without a clear cause reported by occupants of a building. In the 1990s the term "functional somatic syndromes" was applied to several syndromes, including SBS, multiple chemical sensitivity, repetition stress injury, the side effects of silicone breast implants, the Gulf War syndrome (GWS), chronic fatigue syndrome, the irritable bowel syndrome, and fibromyalgia. Recently, Shoenfeld and Agmon-Levin suggested that four conditions--siliconosis, macrophagic myofascitis, the GWS, and post-vaccination phenomena--which share clinical and pathogenic resemblances, may be included under a common syndrome entitled the "autoimmune (auto-inflammatory) syndrome induced by adjuvants". Comparison of the clinical manifestations, symptoms, and signs of the four conditions described by Shoenfeld and Agmon-Levin with those described for SBS shows that nine out of ten main symptoms are present in all 5 conditions. Shoenfeld and Agmon-Levin further propose several major and minor criteria, which, although requiring further validation, may aid in the diagnosis of this newly defined syndrome. We propose here that SBS may also be included as a part of "Shoenfeld's syndrome".

  17. Paraoxonase 1 (PON1) reduces macrophage inflammatory responses.

    PubMed

    Aharoni, Saar; Aviram, Michael; Fuhrman, Bianca

    2013-06-01

    Paraoxonase 1 (PON1) was suggested to play an anti-inflammatory role. In the present study we questioned whether PON1 has a direct impact on macrophage inflammatory responses, and the possible functional implications of such effects. Ex-vivo studies were performed with bone marrow-derived macrophages (BMDM) harvested from C57BL/6 and human-PON1 transgenic (PON1-Tg) mice, and for the in vitro studies the J774.A1 macrophage-like cell line was used. Pro-inflammatory (M1) activation was induced by LPS and INFγ. The spontaneous and M1-induced TNFα and IL-6 secretion were significantly reduced in BMDM derived from PON1-Tg vs. C57BL/6 mice. In vitro, PON1 dose-dependently attenuated both the spontaneous and M1-induced TNFα and IL-6 secretion, and contributed to the anti-inflammatory activity of HDL. Functionally, PON1 attenuated M1-induced production of reactive oxygen species (ROS), phagocytosis, and necrotic macrophage death. PON1 anti-inflammatory activity was mediated, at least in part, via binding to SR-BI, but was independent of the enzyme catalytic activity or of cholesterol efflux stimulation, and did not involve binding to ABCA1. The present study demonstrates, for the first time, that PON1 directly suppresses macrophage pro-inflammatory responses. These findings suggest that PON1 decreases sustained pro-inflammatory reactions, which subsequently can attenuate plaque progression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. COMPARTMENTALIZATION OF THE INFLAMMATORY RESPONSE TO INHALED GRAIN DUST

    EPA Science Inventory


    Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower...

  19. COMPARTMENTALIZATION OF THE INFLAMMATORY RESPONSE TO INHALED GRAIN DUST

    EPA Science Inventory


    Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower...

  20. The consequences for human reproduction of a robust inflammatory response.

    PubMed

    Ness, Roberta B

    2004-12-01

    Innate and adaptive immune responsiveness is variable within the population. Since robust immune reactions are critical to the survival of humans, the existence of immune variability in the population suggests the existence of competing, alternative phenotypes. Although women with powerful immune responsiveness may be more likely to survive to reproduce, their reproductive experiences may be less successful than women who are not as responsive. Normal pregnancy elicits a maternal inflammatory reaction. This can be understood on the basis of maternal-fetal conflict theory: inflammation is a component of the maternal attempt to limit excessive fetal demands. However, an overly aggressive inflammatory reaction has been shown to relate to a variety of adverse reproductive outcomes. Reviewed here are several examples, including the fallopian tube damage that results from pelvic inflammatory disease, the upregulated inflammatory response among women who develop preeclampsia, an association between immune hyperresponsiveness and premature delivery, and the relationship between autoimmune diseases and multiple adverse pregnancy outcomes. The hypothesis that immune hyperresponsiveness limits reproductive capacity suggests many avenues for research.

  1. Extracellular Cyclophilins Contribute to the Regulation of Inflammatory Responses1

    PubMed Central

    Arora, Kamalpreet; Gwinn, William M.; Bower, Molly A.; Watson, Alan; Okwumabua, Ifeanyi; MacDonald, H. Robson; Bukrinsky, Michael I.; Constant, Stephanie L.

    2010-01-01

    The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases. PMID:15972687

  2. Immune Responses to Intestinal Microbes in Inflammatory Bowel Diseases.

    PubMed

    Hansen, Jonathan J

    2015-10-01

    Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are characterized by chronic, T-cell-mediated inflammation of the gastrointestinal tract that can cause significant, lifelong morbidity. Data from both human and animal studies indicate that IBDs are likely caused by dysregulated immune responses to resident intestinal microbes. Certain products from mycobacteria, fungi, and Clostridia stimulate increased effector T cell responses during intestinal inflammation, whereas other bacterial products from Clostridia and Bacteroides promote anti-inflammatory regulatory T cell responses. Antibody responses to bacterial and fungal components may help predict the severity of IBDs. While most currently approved treatments for IBDs generally suppress the patient's immune system, our growing understanding of microbial influences in IBDs will likely lead to the development of new diagnostic tools and therapies that target the intestinal microbiota.

  3. Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

    PubMed

    Arnett, S V; Clark, I A

    2012-12-10

    Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management.

  4. Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure.

    PubMed

    Gomez, Christian R; Hirano, Stefanie; Cutro, Brent T; Birjandi, Shirin; Baila, Horea; Nomellini, Vanessa; Kovacs, Elizabeth J

    2007-01-01

    The aged population is at a higher risk of mortality as a result of complications of injury or infection, such as acute lung injury. The objective of this study was to analyze pulmonary inflammatory responses in young and aged mice after administration of lipopolysaccharide. Prospective, controlled laboratory study. Animal resource facilities and research laboratory. Young (2-3 months old) and aged (18-20 months old) female BALB/c mice. Animals received intraperitoneal injection of lipopolysaccharide derived from Pseudomonas aeruginosa. Control mice received saline alone. After 24 hrs, mice were killed. Pulmonary neutrophil infiltration was assessed histologically and by myeloperoxidase activity. Pulmonary levels of the CXC chemokines, monocyte inflammatory protein-2 and KC, and cytokines, tumor necrosis factor-alpha and interleukin-1beta, were assessed by enzyme-linked immunosorbent assay. Lungs of aged mice given lipopolysaccharide showed a six-fold higher neutrophil infiltration and three-fold higher level of myeloperoxidase activity than lungs of young mice given lipopolysaccharide. Pulmonary levels of monocyte inflammatory protein-2 and KC were significantly higher in the lungs of aged mice given lipopolysaccharide, compared with younger mice. Levels of tumor necrosis factor-alpha and interleukin-1beta in the lung were analyzed as well. After lipopolysaccharide treatment, there was no difference in the level of tumor necrosis factor-alpha in lungs of young and aged animals, but interleukin-1beta was two-fold higher in the lungs of the aged group. These data suggest that at this time point, interleukin-1beta may contribute to the higher production of CXC chemokines observed in lungs of aged mice vs. young mice receiving lipopolysaccharide. The hyperreactive systemic inflammatory response seen in aged individuals after lipopolysaccharide administration is accompanied by an exacerbated pulmonary inflammatory response, which may contribute to the higher mortality

  5. Mechanical ventilation increases the inflammatory response induced by lung contusion.

    PubMed

    van Wessem, Karlijn J P; Hennus, Marije P; van Wagenberg, Linda; Koenderman, Leo; Leenen, Luke P H

    2013-07-01

    Posttraumatic lung contusion is common after blunt chest trauma, and patients often need ventilatory support. Lung contusion induces an inflammatory response signified by primed polymorph neutrophil granulocytes (PMNs) in blood and tissue. Mechanical ventilation (MV) can also cause an inflammatory response. The aim of this study was to develop an animal model to investigate the effect of high-volume ventilation on the inflammatory response in blunt chest trauma. We assigned 23 male Sprague-Dawley rats to either MV or bilateral lung contusion followed by MV. We used three extra rats as controls. Lung contusion was induced by a blast generator, a device releasing a single pressure blast wave centered on the chest. We determined tissue and systemic inflammation by absolute PMN numbers in blood and bronchoalveolar lavage fluid (BALF), myeloperoxidase, interleukin (IL)-6, IL 1β, growth-related oncogene-KC, and IL-10 in both plasma and BALF. Survival after blunt chest trauma was correlated to the distance to the blast generator. Compared with controls, both MV and blast plus MV rats showed increased systemic and pulmonary inflammation, expressed by higher PMNs, myeloperoxidase levels, and cytokine levels in both blood and BALF. Blast plus MV rats showed a higher systemic and pulmonary inflammatory response than MV rats. The blast generator generated reproducible blunt chest trauma in rats. Mechanical ventilation after lung contusion induced a larger overall inflammatory response than MV alone, which indicates that local damage contributes not only to local inflammation, but also to systemic inflammation. This emphasizes the importance of lung protective ventilation strategies after pulmonary contusion. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Colchicine-responsive protracted gouty arthritis with systemic inflammatory reactions.

    PubMed

    Nonaka, Fumiaki; Migita, Kiyoshi; Haramura, Tomoko; Sumiyoshi, Remi; Kawakami, Atsushi; Eguchi, Katsumi

    2014-05-01

    Acute gouty arthritis is a severe but self-limiting arthritis caused by inflammatory responses to urate crystals. Oral colchicines are effective for initial stages or prophylaxis, but generally, colchicines are ineffective for established gouty arthritis. We describe an unusual case of gouty arthritis with systemic inflammatory reactions, including high fever and polymyalgia. Refractory polyarthritis and high fever were eradicated by colchicine treatment. Genetic analysis revealed a heterozygous mutation in exon 2 of the MEFV gene (E148Q). This case underscores the possibility that MEFV gene mutations may modify the phenotype of gouty arthritis.

  7. Platelets protect lung from injury induced by systemic inflammatory response

    PubMed Central

    Luo, Shuhua; Wang, Yabo; An, Qi; Chen, Hao; Zhao, Junfei; Zhang, Jie; Meng, Wentong; Du, Lei

    2017-01-01

    Systemic inflammatory responses can severely injure lungs, prompting efforts to explore how to attenuate such injury. Here we explored whether platelets can help attenuate lung injury in mice resulting from extracorporeal circulation (ECC)-induced systemic inflammatory responses. Mice were subjected to ECC for 30 min, then treated with phosphate-buffered saline, platelets, the GPIIb/IIIa inhibitor Tirofiban, or the combination of platelets and Tirofiban. Blood and lung tissues were harvested 60 min later, and lung injury and inflammatory status were assessed. As expected, ECC caused systemic inflammation and pulmonary dysfunction, and platelet transfusion resulted in significantly milder lung injury and higher lung function. It also led to greater numbers of circulating platelet-leukocyte aggregates and greater platelet accumulation in the lung. Platelet transfusion was associated with higher production of transforming growth factor-β and as well as lower levels of tumour necrosis factor-α and neutrophil elastase in plasma and lung. None of these platelet effects was observed in the presence of Tirofiban. Our results suggest that, at least under certain conditions, platelets can protect lung from injury induced by systemic inflammatory responses. PMID:28155889

  8. Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses.

    PubMed

    Jacob, Fenila; Pérez Novo, Claudina; Bachert, Claus; Van Crombruggen, Koen

    2013-09-01

    Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions.

  9. Early development of immune reconstitution inflammatory syndrome related to Pneumocystis pneumonia after antiretroviral therapy.

    PubMed

    Mok, Hoi Ping; Hart, Elizabeth; Venkatesan, Pradhib

    2014-04-01

    Immune reconstitution inflammatory syndrome is a recognized complication after the initiation of combination antiretroviral therapy (cART). We report a patient who developed life-threatening pulmonary immune reconstitution inflammatory syndrome (IRIS) three days after initiation of cART. We reviewed published cases of IRIS after Pneumocystis pneumonia (PCP), in particular the time from initiation of cART to IRIS event. The median duration from the initiation of cART to the onset of IRIS was 15 days in the 33 patients reviewed. This report alerts clinicians to the rapidity of the development of pulmonary IRIS following PCP after the initiation of cART.

  10. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses

    PubMed Central

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Dolores Ledesma, Maria; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria

    2016-01-01

    Summary The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases. PMID:26299452

  11. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome.

    PubMed

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-08-24

    Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  12. Arterial stiffness and inflammatory response to psychophysiological stress.

    PubMed

    Ellins, Elizabeth; Halcox, Julian; Donald, Ann; Field, Bryony; Brydon, Lena; Deanfield, John; Steptoe, Andrew

    2008-08-01

    The processes through which psychological stress influences cardiovascular disease are poorly understood, but may involve activation of hemodynamic, neuroendocrine and inflammatory responses. We assessed the relationship between carotid arterial stiffness and inflammatory responses to acute psychophysiologic stress. Participants were 155 healthy men and women aged 55.3, SD 2.7 years. Blood samples for the assessment of plasma fibrinogen, tumor necrosis factor (TNF) alpha and interleukin (IL) 6 were drawn at baseline, immediately following standardized behavioral tasks, and 45 min later. Carotid artery stiffness was measured ultrasonically three years later, and blood pressure and heart rate responses were recorded. The tasks induced substantial increases in blood pressure and heart rate, together with increased fibrinogen, TNFalpha and IL-6 concentration. Carotid stiffness was positively associated with body mass, waist/hip ratio, blood pressure, low density lipoprotein cholesterol, and C-reactive protein, and inversely with high density lipoprotein and grade of employment. Baseline levels of inflammatory variables were not related to carotid artery stiffness. But carotid stiffness was greater in participants with larger fibrinogen (p=0.037) and TNFalpha (p=0.036) responses to psychophysiological stress. These effects were independent of age, gender, grade of employment, smoking, body mass, waist/hip ratio, systolic and diastolic pressure, high and low density lipoprotein cholesterol, and C-reactive protein. There were no associations between carotid stiffness and stress responses in IL-6, blood pressure, or heart rate. We conclude that individual differences in inflammatory responses to psychophysiological stress are independently related to structural changes in artery walls that reflect increased cardiovascular disease risk.

  13. Pathogenesis of the immune reconstitution inflammatory syndrome affecting the central nervous system in patients infected with HIV.

    PubMed

    Martin-Blondel, Guillaume; Delobel, Pierre; Blancher, Antoine; Massip, Patrice; Marchou, Bruno; Liblau, Roland S; Mars, Lennart T

    2011-04-01

    Anti-retroviral therapy partially restores the immune function of patients infected with human immunodeficiency virus, thereby drastically reducing morbidity and mortality. However, the clinical condition of a subset of patients on anti-retroviral therapy secondarily deteriorates due to an inflammatory process termed immune reconstitution inflammatory syndrome. This condition results from the restoration of the immune system that upon activation can be detrimental to the host. Among the various clinical manifestations, central nervous system involvement is associated with greater morbidity and mortality. This review covers the pathogenesis of this novel neuroinflammatory disease, including the nature of the provoking pathogens and the composition and specificity of the evoked immune responses. Our current perception of this neuroinflammatory disease supports therapeutic strategies aimed at modulating immune aggression without dampening the life-saving restoration of the immune response.

  14. Anti-inflammatory treatment of meconium aspiration syndrome: benefits and risks.

    PubMed

    Mokra, Daniela; Mokry, Juraj; Tonhajzerova, Ingrid

    2013-06-01

    Meconium aspiration syndrome (MAS) is a major cause of respiratory insufficiency in the term and post-term newborns. There are several pathomechanisms participating in this disorder, particularly the airway obstruction, surfactant dysfunction, inflammation, lung edema, pulmonary vasoconstriction and bronchoconstriction. Inflammatory changes resulting from meconium aspiration cause severe impairment of lung parenchyma and surfactant, and influence the reactivity of both vascular and airway smooth muscle. Therefore, anti-inflammatory drugs may be of benefit in the management of MAS. This article reviews the pharmacological actions and side effects of various anti-inflammatory drugs used up to now in the experimental models of MAS and in the treatment of newborns with meconium aspiration.

  15. Inflammatory and immune responses in the arterial media.

    PubMed

    Tellides, George; Pober, Jordan S

    2015-01-16

    Inflammatory arterial diseases differentially affect the compartments of the vessel wall. The intima and adventitia are commonly involved by the disease process, with luminal and microvascular endothelial cells playing a critical role in the recruitment and activation of leukocytes. In contrast, the avascular media is often spared by immune-mediated disorders. Surprisingly, vascular smooth muscle cells (VSMCs), the predominant and often exclusive cell type of the media, are capable of robust proinflammatory responses to diverse stressors. The multiple cytokines and chemokines produced within the media can profoundly affect macrophage and T cell function, thus amplifying and shaping innate and adaptive immune responses. On the other hand, VSMCs and the extracellular matrix that they produce also display significant anti-inflammatory properties. The balance between the pro- and anti-inflammatory effects of VSMCs and their extracellular matrix versus the strength of the inciting immunologic events determines the pattern of medial pathology. Limitations on the extent of medial infiltration and injury, defined as medial immunoprivilege, are typically seen in arteriosclerotic diseases, such as atherosclerosis and transplant vasculopathy. Conversely, breakdown of medial immunoprivilege that manifests as more intense leukocytic infiltrates, loss of VSMCs, and destruction of the extracellular matrix architecture is a general feature of certain aneurysmal diseases and vasculitides. In this review, we consider the inflammatory and immune functions of VSMCs and how they may lead to medial immunoprivilege or medial inflammation in arterial diseases. © 2015 American Heart Association, Inc.

  16. Oncostatin M in the anti-inflammatory response

    PubMed Central

    Wahl, A; Wallace, P

    2001-01-01

    Oncostatin M (OM) is a pleiotropic cytokine of the interleukin 6 family, whose in vivo properties and physiological function remain in dispute and poorly defined. These in vivo studies strongly suggest that OM is anabolic, promoting wound healing and bone formation, and anti-inflammatory. In models of inflammation OM is produced late in the cytokine response and protects from lipopolysaccharide (LPS)-induced toxicities, promoting the re-establishment of homoeostasis by cooperating with proinflammatory cytokines and acute phase molecules to alter and attenuate the inflammatory response. Administration of OM inhibited bacterial LPS-induced production of tumour necrosis factor α and septic lethality in a dose dependent manner. Consistent with these findings, in animal models of chronic inflammatory disease OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and antibody production were not impaired by OM treatment. Taken together, these data indicate that the activities of this cytokine in vivo are anti-inflammatory without concordant immunosuppression.

 PMID:11890661

  17. Blau syndrome, the prototypic auto-inflammatory granulomatous disease.

    PubMed

    Wouters, Carine H; Maes, Anne; Foley, Kevin P; Bertin, John; Rose, Carlos D

    2014-01-01

    Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau granuloma. Finally, emerging insights into pathogenic mechanisms including activation of NOD2 signal transduction, and potential biomarkers of disease activity are discussed.

  18. Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2 Microglia

    PubMed Central

    Bozic, Iva; Savic, Danijela; Laketa, Danijela; Bjelobaba, Ivana; Milenkovic, Ivan; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may

  19. Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study.

    PubMed

    Fernández-Bergés, Daniel; Consuegra-Sánchez, Luciano; Peñafiel, Judith; Cabrera de León, Antonio; Vila, Joan; Félix-Redondo, Francisco Javier; Segura-Fragoso, Antonio; Lapetra, José; Guembe, María Jesús; Vega, Tomás; Fitó, Montse; Elosua, Roberto; Díaz, Oscar; Marrugat, Jaume

    2014-08-01

    There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. Th2 and eosinophil responses suppress inflammatory arthritis

    PubMed Central

    Chen, Zhu; Andreev, Darja; Oeser, Katharina; Krljanac, Branislav; Hueber, Axel; Kleyer, Arnd; Voehringer, David; Schett, Georg; Bozec, Aline

    2016-01-01

    Th2–eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2–eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis. PMID:27273006

  1. Associations between periodontitis and systemic inflammatory diseases: response to treatment.

    PubMed

    El-Shinnawi, Una; Soory, Mena

    2013-09-01

    There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship

  2. Post-mating inflammatory responses of the uterus.

    PubMed

    Katila, T

    2012-08-01

    This review attempts to summarize the current knowledge on uterine inflammatory response after mating in horses, pigs and cattle. Post-mating endometritis has been extensively studied in horses as it has been considered to cause infertility. The inflammation is known to occur also in cattle, but it has not been investigated to a similar extent. There are a number of publications about mechanisms of post-mating uterine inflammation in pigs, which seem to resemble those in horses. The major focus of this review is the horse, but relevant literature is presented also on swine and cattle. Spermatozoa, seminal plasma and semen extenders play roles in the induction of inflammation. In addition, sperm numbers, concentration and viability, as well as the site of semen deposition may modulate the inflammatory response. Cytokines, polymorphonuclear leucocytes (PMN) and mononuclear cells represent the uterine inflammatory response to mating. Inflammation is the first line of defence against invasion and eliminates excess spermatozoa and bacteria. Semen deposition elicits a massive PMN invasion, followed by phagocytosis of sperm aided by the formation of neutrophil extracellular traps. Exposure of the female genital tract to semen is important also for endometrial receptivity and pre-implantation embryo development. Seminal plasma (SP) and inflammation elicit transient immune tolerance to antigens present in semen. SP contains immune-regulatory molecules that activate and control immune responses to antigens by stimulating expression of cytokines and growth factors and by initiating tissue remodelling. SP also regulates ovarian function. Effective elimination of excess sperm and inflammatory by-products and subsequent rapid return of the endometrium to the normal state is a prerequisite for pregnancy. Uterine backflow, driven by myometrial contractions and requiring a patent cervix, is an important physical tool in uterine drainage.

  3. The role of Peroxiredoxin 4 in inflammatory response and aging

    PubMed Central

    Klichko, Vladimir I.; Orr, William C.; Radyuk, Svetlana N.

    2015-01-01

    In prior studies, we determined that moderate overexpression of the Drosophila endoplasmic reticulum (ER)-localized peroxiredoxin (Prx), dPrx4, reduced oxidative damage and conferred beneficial effects on lifespan, while high level expression increased the incidence of tissue-specific apoptosis and dramatically shortened longevity. The detrimental pro-apoptotic and life-shortening effects were attributed to aberrant localization of dPrx4 and the apparent ER stress elicited by dPrx4 overexpression. In addition, activation of both the NF-κB- and JAK/STAT- mediated stress responses was detected, although it wasn’t clear whether these served as functional alarm signals. Here we extend these findings to show that activation of the NF-κB -dependent immunity-related/inflammatory genes, associated with lifespan shortening effects, is dependent on the activity of a Drosophila NF-κB ortholog, Relish. In the absence of Relish, the pro-inflammatory effects typically elicited by dPrx4 overexpression were not detected. The absence of Relish not only prevented hyperactivation of the immunity-related genes but also significantly rescued the severe shortening of lifespan normally observed in dPrx4 over-expressors. Overactivation of the immune/inflammatory responses was also lessened by JAK/STAT signaling. In addition we found that cellular immune/pro-inflammatory responses provoked by the oxidant paraquat but not bacteria are mediated via dPrx4 activity in the ER, as up-regulation of the immune-related genes was eliminated in flies underexpressing dPrx4 whereas immune responses triggered by bacteria were unaffected. Finally, efforts to reveal critical tissues where dPrx4 modulates longevity showed that broad targeting of dPrx4 to neuronal tissue had strong beneficial effects, while targeting expression to the fat body had deleterious effects. PMID:26689888

  4. Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses

    PubMed Central

    Ashbrook, M J; McDonough, K L; Pituch, J J; Christopherson, P L; Cornell, T T; Selewski, D T; Shanley, T P; Blatt, N B

    2015-01-01

    Citrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but the ability of exogenous citrate to impact inflammatory signalling cascades remains largely unknown. We hypothesized that citrate would modulate inflammatory responses as both a cellular metabolite and calcium chelator, and tested this hypothesis by determining how clinically relevant levels of citrate modulate monocyte proinflammatory responses to lipopolysaccharide (LPS) in a human acute monocytic leukaemia cell line (THP-1). In normal medium (0·4 mM calcium), citrate inhibited LPS-induced tumour necrosis factor (TNF)-α and interleukin (IL)-8 transcripts, whereas in medium supplemented with calcium (1·4 mM), TNF-α and IL-8 levels increased and appeared independent of calcium chelation. Using an IL-8–luciferase plasmid construct, the same increased response was observed in the activation of the IL-8 promoter region, suggesting transcriptional regulation. Tricarballylic acid, an inhibitor of ATP-citrate lyase, blocked the ability of citrate to augment TNF-α, linking citrate's augmentation effect with its metabolism by ATP-citrate lyase. In the presence of citrate, increased histone acetylation was observed in the TNF-α and IL-8 promoter regions of THP-1 cells. We observed that citrate can both augment and inhibit proinflammatory cytokine production via modulation of inflammatory gene transactivation. These findings suggest that citrate anti-coagulation may alter immune function through complex interactions with the inflammatory response. PMID:25619261

  5. Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells

    PubMed Central

    Palmieri, Erika M.; Menga, Alessio; Lebrun, Aurore; Hooper, Douglas C.; Butterfield, D. Allan

    2017-01-01

    Abstract Aims: Microglial cells are brain-resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to lipopolysaccharide (LPS) activation in other cell types, which is expressed by microglia. Results: GS inhibition enhances release of inflammatory mediators of LPS-activated microglia in vitro, leading to perturbation of the redox balance and decreased viability of cocultured neurons. GS inhibition also decreases insulin-mediated glucose uptake in microglia. In vivo, microglia-specific GS ablation enhances expression of inflammatory markers upon LPS treatment. In the spinal cords from experimental autoimmune encephalomyelitis (EAE), GS expression levels and glutamine/glutamate ratios are reduced. Innovation: Recently, metabolism has been highlighted as mediator of immune cell function through the discovery of mechanisms that (behind these metabolic changes) modulate the inflammatory response. The present study shows for the first time a metabolic mechanism mediating microglial response to a proinflammatory stimulus, pointing to GS activity as a master modulator of immune cell function and thus unraveling a potential therapeutic target. Conclusions: Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention. Antioxid. Redox Signal. 26, 351–363. PMID:27758118

  6. Immune reconstitution inflammatory syndrome presenting as secondary syphilis with polymorphous erythema and knee arthritis.

    PubMed

    Brochard, J; Khatchatourian, L; Woaye-Hune, P; Biron, C; Lefebvre, M; Denis-Musquer, M; Grange, P; Dupin, N; Raffi, F

    2017-03-08

    Syphilis and HIV are strongly linked to one another and immune reconstitution inflammatory syndrome (IRIS) after antiretroviral therapy (ART) initiation can complicate matters. A 24-years-old homosexual man was hospitalized for fever, cough and headache. HIV infection had been diagnosed 5 years earlier but he discontinued ART for the last 2 years. This article is protected by copyright. All rights reserved.

  7. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing.

  8. The cellular inflammatory response in human spinal cords after injury.

    PubMed

    Fleming, Jennifer C; Norenberg, Michael D; Ramsay, David A; Dekaban, Gregory A; Marcillo, Alexander E; Saenz, Alvaro D; Pasquale-Styles, Melissa; Dietrich, W Dalton; Weaver, Lynne C

    2006-12-01

    Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were 'dead at the scene' or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1-3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil alpha-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1-3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1-3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8(+) lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative

  9. Irritable bowel syndrome and inflammatory bowel disease overlap syndrome: pieces of the puzzle are falling into place

    PubMed Central

    Abdul Rani, Rafiz; Raja Ali, Raja Affendi

    2016-01-01

    Irritable bowel syndrome (IBS), a common gastrointestinal disorder involving the gut-brain axis, and inflammatory bowel disease (IBD), a chronic relapsing inflammatory disorder, are both increasing in incidence and prevalence in Asia. Both have significant overlap in terms of symptoms, pathophysiology, and treatment, suggesting the possibility of IBS and IBD being a single disease entity albeit at opposite ends of the spectrum. We examined the similarities and differences in IBS and IBD, and offer new thoughts and approaches to the disease paradigm. PMID:27799880

  10. Nerve abscess in Hansen's disease as part of immune reconstitution inflammatory syndrome: a case report.

    PubMed

    Ali, Neema M; Nayak, Kashinath; Kumar, Pramod

    2017-02-01

    Immune reconstitution inflammatory syndrome is an inflammatory reaction in HIV-infected patients after initiation of antiretroviral therapy resulting from restored immunity to specific infectious or non-infectious antigens. A 36-year-old male patient on highly active antiretroviral therapy of six months duration, presented with reddish, tender lesions over medial aspect of arm and a single, anaesthetic patch. Tender fluctuant swellings were seen on the medial aspect of left forearm. A few of them had ruptured spontaneously discharging pus. A skin biopsy from the anaesthetic patch showed caseating epitheloid granulomas. A diagnosis of Hansen's disease borderline tuberculoid in type 1 reversal reaction, with formation of nerve abscess due to Immune Reconstitution Inflammatory Syndrome was made. The patient was started on multibacillary multidrug therapy as per WHO guidelines and highly active antiretroviral therapy was continued.

  11. Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

    PubMed Central

    Morris, Gerwyn; Maes, Michael

    2014-01-01

    Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease. PMID:24669210

  12. Palmitate promotes inflammatory responses and cellular senescence in cardiac fibroblasts.

    PubMed

    Sokolova, Marina; Vinge, Leif Erik; Alfsnes, Katrine; Olsen, Maria Belland; Eide, Lars; Kaasbøll, Ole Jørgen; Attramadal, Håvard; Torp, May-Kristin; Fosshaug, Linn E; Rashidi, Azita; Lien, Egil; Finsen, Alexandra Vanessa; Sandanger, Øystein; Aukrust, Pål; Ranheim, Trine; Yndestad, Arne

    2017-02-01

    Palmitate triggers inflammatory responses in several cell types, but its effects on cardiac fibroblasts are at present unknown. The aims of the study were to (1) assess the potential of palmitate to promote inflammatory signaling in cardiac fibroblasts through TLR4 and the NLRP3 inflammasome and (2) characterize the cellular phenotype of cardiac fibroblasts exposed to palmitate. We examined whether palmitate induces inflammatory responses in cardiac fibroblasts from WT, NLRP3(-/-) and ASC(-/-)mice (C57BL/6 background). Exposure to palmitate caused production of TNF, IL-6 and CXCL2 via TLR4 activation. NLRP3 inflammasomes are activated in a two-step manner. Whereas palmitate did not prime the NLRP3 inflammasome, it induced activation in LPS-primed cardiac fibroblasts as indicated by IL-1β, IL-18 production and NLRP3-ASC co-localization. Palmitate-induced NLRP3 inflammasome activation in LPS-primed cardiac fibroblasts was associated with reduced AMPK activity, mitochondrial reactive oxygen species production and mitochondrial dysfunction. The cardiac fibroblast phenotype caused by palmitate, in an LPS and NLRP3 independent manner, was characterized by decreased cellular proliferation, contractility, collagen and MMP-2 expression, as well as increased senescence-associated β-galactosidase activity, and consistent with a state of cellular senescence. This study establishes that in vitro palmitate exposure of cardiac fibroblasts provides inflammatory responses via TLR4 and NLRP3 inflammasome activation. Palmitate also modulates cardiac fibroblast functionality, in a NLRP3 independent manner, resulting in a phenotype related to cellular senescence. These effects of palmitate could be of importance for myocardial dysfunction in obese and diabetic patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Inflammatory Biomarkers as Differential Predictors of Antidepressant Response

    PubMed Central

    Hashimoto, Kenji

    2015-01-01

    Although antidepressants are generally effective in the treatment of major depressive disorder (MDD), it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. PMID:25856677

  14. Inflammatory biomarkers as differential predictors of antidepressant response.

    PubMed

    Hashimoto, Kenji

    2015-04-08

    Although antidepressants are generally effective in the treatment of major depressive disorder (MDD), it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine.

  15. The Inflammatory Response in Psoriasis: a Comprehensive Review.

    PubMed

    Deng, Yaxiong; Chang, Christopher; Lu, Qianjin

    2016-06-01

    Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis. The interplay of immune cells and cytokines is another critical factor in the pathogenesis of psoriasis. These factors or pathways include Th1/Th2 homeostasis, the Th17/Treg balance and the IL-23/Th17 axis. Th17 is believed particularly important in psoriasis due to its pro-inflammatory effects and its involvement in an integrated inflammatory loop with dendritic cells and keratinocytes, contributing to an overproduction of antimicrobial peptides, inflammatory cytokines, and chemokines that leads to amplification of the immune response. In addition, other pathways and signaling molecules have been found to be involved, including Th9, Th22, regulatory T cells, γδ T cells, CD8(+) T cells, and their related cytokines. Understanding the pathogenesis of psoriasis will allow us to develop increasingly efficient targeted treatment by blocking relevant inflammatory signaling pathways and molecules. There is no cure for psoriasis at the present time, and much of the treatment involves managing the symptoms. The biologics, while lacking the adverse effects associated with some of the traditional medications such as corticosteroids and methotrexate, have their own set of side effects, which may include reactivation of latent infections. Significant challenges remain in developing safe and efficacious novel targeted therapies that depend on a better understanding of the immunological dysfunction in psoriasis.

  16. Neither classical nor alternative macrophage activation is required for Pneumocystis clearance during immune reconstitution inflammatory syndrome.

    PubMed

    Zhang, Zhuo-Qian; Wang, Jing; Hoy, Zachary; Keegan, Achsah; Bhagwat, Samir; Gigliotti, Francis; Wright, Terry W

    2015-12-01

    Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4(+) T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2(-/-) mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2(-/-) mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-γR(-/-) nor RAG/IL-4Rα(-/-) mice displayed impaired Pneumocystis clearance. However, RAG/IFN-γR(-/-) mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα(-/-) mice. RAG/IFN-γR(-/-) mice had elevated numbers of lung CD4(+) T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8(+) T suppressor cells. Impaired lung CD8(+) T cell responses in RAG/IFN-γR(-/-) mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8(+) T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS.

  17. Hypercortisolemia in acute stroke is related to the inflammatory response.

    PubMed

    Slowik, Agnieszka; Turaj, Wojciech; Pankiewicz, Joanna; Dziedzic, Tomasz; Szermer, Paweł; Szczudlik, Andrzej

    2002-04-15

    Hypercortisolemia is thought to be a marker of the stress response following stroke. The aim of this study was to investigate the prevalence and prognostic significance of hypercortisolemia. The circadian variation of cortisol level and the relationship between serum cortisol levels and other stress, inflammatory, and haemostatic markers were also investigated. Seventy consecutive patients with their first ischemic stroke and 24 age- and sex-matched controls were included in the study. Serum cortisol levels (at 6:00 AM, 10:00 AM, 6:00 PM, and 10:00 PM), 24-h urine catecholamine excretion, beta-thromboglobulin levels, and other standard biochemical and haematological parameters were measured on the first day of hospitalisation and in control subjects. Outcome measures used the Barthel Index at Day 30, as well as 30- and 90-day mortality rates. Hypercortisolemia, defined as at least two of the four measurements above the normal range of serum cortisol levels (i.e. >618 nmol/l from the morning samples and >460 nmol/l from the evening samples) was found in 25 (35.7%) of the acute stroke patients and in 3 (12.5%) of the controls (p<0.05). Hypercortisolemia was associated with older age, greater severity of neurological deficit, larger ischemic lesions on CT, and worse prognoses (p<0.05). The study did not find a correlation between serum cortisol levels and other markers of the stress response such as catecholamines excretion and glucose levels. A significant correlation between serum cortisol levels and some markers of the inflammatory response, such as fever, fibrinogen level, white blood cell (WBC) count, and beta-thromboglobulin level, was established in stroke patients. Prognostic significance of hypercortisolemia in acute stroke patients seems to be related to the inflammatory response rather than to the stress response.

  18. Role of moesin in HMGB1-stimulated severe inflammatory responses.

    PubMed

    Lee, W; Kwon, O K; Han, M-S; Lee, Y-M; Kim, S-W; Kim, K-M; Lee, T; Lee, S; Bae, J-S

    2015-08-01

    Sepsis is a life-threatening condition that arises when the body's response to infection causes systemic inflammation. High-mobility group box 1 (HMGB1), as a late mediator of sepsis, enhances hyperpermeability, and it is therefore a therapeutic target. Despite extensive research into the underlying mechanisms of sepsis, the target molecules controlling vascular leakage remain largely unknown. Moesin is a cytoskeletal protein involved in cytoskeletal changes and paracellular gap formation. The objectives of this study were to determine the roles of moesin in HMGB1-mediated vascular hyperpermeability and inflammatory responses and to investigate the mechanisms of action underlying these responses. Using siRNA knockdown of moesin expression in primary human umbilical vein endothelial cells (HUVECs), moesin was found to be required in HMGB1-induced F-actin rearrangement, hyperpermeability, and inflammatory responses. The mechanisms involved in moesin phosphorylation were analysed by blocking the binding of the HMGB1 receptor (RAGE) and inhibiting the Rho and MAPK pathways. HMGB1-treated HUVECs exhibited an increase in Thr558 phosphorylation of moesin. Circulating levels of moesin were measured in patients admitted to the intensive care unit with sepsis, severe sepsis, and septic shock; these patients showed significantly higher levels of moesin than healthy controls, which was strongly correlated with disease severity. High blood moesin levels were also observed in cecal ligation and puncture (CLP)-induced sepsis in mice. Administration of blocking moesin antibodies attenuated CLP-induced septic death. Collectively, our findings demonstrate that the HMGB1-RAGE-moesin axis can elicit severe inflammatory responses, suggesting it to be a potential target for the development of diagnostics and therapeutics for sepsis.

  19. HETEROGENEITY OF SYSTEMIC INFLAMMATORY RESPONSES TO PERIODONTAL THERAPY

    PubMed Central

    Behle, Jan H.; Sedaghatfar, Michael H.; Demmer, Ryan T.; Wolf, Dana L.; Celenti, Romanita; Kebschull, Moritz; Belusko, Paul B.; Herrera-Abreu, Miriam; Lalla, Evanthia; Papapanou, Panos N.

    2009-01-01

    Aims We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers. Methods Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6-week period. Blood samples were obtained at: one week pre- therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analyzed using checkerboard hybridizations. Results At T3, PAI-1, sE-selectin, sVCAM-1, MMP-9, myeloperoxidase, and a composite Summary Inflammatory Score (SIS) were significantly reduced. However, only sE-selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced marked reduction and pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis. Conclusions Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further. PMID:19426174

  20. Heterogeneity of systemic inflammatory responses to periodontal therapy.

    PubMed

    Behle, Jan H; Sedaghatfar, Michael H; Demmer, Ryan T; Wolf, Dana L; Celenti, Romanita; Kebschull, Moritz; Belusko, Paul B; Herrera-Abreu, Miriam; Lalla, Evanthia; Papapanou, Panos N

    2009-04-01

    We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers. Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6-week period. Blood samples were obtained at: 1-week pre-therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed the plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analysed using checkerboard hybridizations. At T3, PAI-1, sE-selectin, sVCAM-1, MMP-9, myeloperoxidase, and a composite summary inflammatory score (SIS) were significantly reduced. However, only sE-selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced a marked reduction and a pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis. Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further.

  1. Inflammatory responses in the rat superior colliculus after eye enucleation.

    PubMed

    Hernandes, Marina S; Britto, Luiz R G

    2014-02-01

    Ocular enucleation induces profound morphological alterations in central visual areas. However, little is known about the response of glial cells and possible inflammatory processes in visual brain areas resulting from eye enucleation. In this study, immunoblotting and immunostaining assays revealed increased expression of astrocyte and microglia markers in the rat superior colliculus (SC) between 1 and 15 days after contralateral enucleation. A transient increase of neuronal COX-2 protein expression was also found in the SC. To evaluate the role of an anti-inflammatory drug in attenuating both COX-2 and glial cell activation, the synthetic glucocorticoid dexamethasone (DEX) was administered (1 mg/kg i.p., for 3 days) to enucleated rats. Immunoblotting data revealed that DEX treatment significantly inhibited COX-2 protein expression. Postlesion immunostaining for astrocyte and microglia markers was also significantly reduced by DEX treatment. These findings suggest that the removal of retinal ganglion cell input generates inflammatory responses in central retinorecipient structures. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Mast cells and nerves tickle in the tummy: implications for inflammatory bowel disease and irritable bowel syndrome.

    PubMed

    Rijnierse, Anneke; Nijkamp, Frans P; Kraneveld, Aletta D

    2007-11-01

    Mast cells are well known as versatile cells capable of releasing and producing a variety of inflammatory mediators upon activation and are often found in close proximity of neurons. In addition, inflammation leads to local activation of neurons resulting in the release neuropeptides, which also play an important immune modulatory role by stimulation of immune cells. In intestinal disorders like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), the number of mast cells is known to be much higher than in the normal intestine. Moreover, both these disorders are also reported to be associated with alterations in neuropeptide content and in neural innervation. Mutual association between mast cells and enteric nerves has been demonstrated to be increased in pathophysiological conditions and contribute to spreading and amplification of the response in IBD and IBS. In this review the focus lies on studies appointed to the direct interaction between mast cells and nerves in IBD, IBS, and animal models for these disorders so far.

  3. Mitochondrial Respiration Controls Lysosomal Function during Inflammatory T Cell Responses.

    PubMed

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Ledesma, Maria Dolores; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria

    2015-09-01

    The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4(+) T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation, and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward proinflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD(+) levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify strategies for intervention in mitochondrial-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

    PubMed

    Tanaka, Ryota; Maruyama, Hiroshi; Tomidokoro, Yasushi; Yanagiha, Kumi; Hirabayashi, Takumi; Ishii, Akiko; Okune, Mari; Inoue, Sae; Sekine, Ikuo; Tamaoka, Akira; Fujimoto, Manabu

    2016-09-01

    Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants.

    PubMed

    Camargos, Ana Cristina Resende; Mendonça, Vanessa Amaral; Andrade, Camila Alves de; Oliveira, Katherine Simone Caires; Tossige-Gomes, Rosalina; Rocha-Vieira, Etel; Neves, Camila Danielle Cunha; Vieira, Érica Leandro Marciano; Leite, Hércules Ribeiro; Oliveira, Murilo Xavier; Júnior, Antônio Lúcio Teixeira; Coimbra, Cândido Celso; Lacerda, Ana Cristina Rodrigues

    2016-01-01

    Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF) and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group) between 6 and 24 months. Plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor (TNF) receptors, chemokines, BDNF, serum cortisol and redox status were measured. Unpaired Student's t-test was used to analyze the results and a probability of p<0.05 was acceptable for rejection of the null hypothesis. The Pearson correlation was used to verify the association between the biomarkers analyzed in each group. Plasma levels of leptin (p = 0.0001), adiponectin (p = 0.0007) and BDNF (p = 0.003), and serum cortisol (p = 0.048) were significantly higher in overweight/obese infants than normal-weight infants. In contrast, the concentration of thiobarbituric acid reactive substances (TBARS) (p = 0.004), and catalase (p = 0.045) and superoxide dismutase activity (p = 0.02) were lower in overweight/obese infants than normal-weight peers. All the results together indicate neuroendocrine inflammatory response changes in overweight/obese infants between 6 and 24 months. Although there is already an environment that predisposes for a subsequent pro-inflammatory response, neuroendocrine secretion changes that permit the control of the inflammatory process in this age interval can be observed.

  6. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants

    PubMed Central

    de Andrade, Camila Alves; Oliveira, Katherine Simone Caires; Tossige-Gomes, Rosalina; Rocha-Vieira, Etel; Neves, Camila Danielle Cunha; Vieira, Érica Leandro Marciano; Leite, Hércules Ribeiro; Oliveira, Murilo Xavier; Júnior, Antônio Lúcio Teixeira; Coimbra, Cândido Celso

    2016-01-01

    Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF) and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group) between 6 and 24 months. Plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor (TNF) receptors, chemokines, BDNF, serum cortisol and redox status were measured. Unpaired Student's t-test was used to analyze the results and a probability of p<0.05 was acceptable for rejection of the null hypothesis. The Pearson correlation was used to verify the association between the biomarkers analyzed in each group. Plasma levels of leptin (p = 0.0001), adiponectin (p = 0.0007) and BDNF (p = 0.003), and serum cortisol (p = 0.048) were significantly higher in overweight/obese infants than normal-weight infants. In contrast, the concentration of thiobarbituric acid reactive substances (TBARS) (p = 0.004), and catalase (p = 0.045) and superoxide dismutase activity (p = 0.02) were lower in overweight/obese infants than normal-weight peers. All the results together indicate neuroendocrine inflammatory response changes in overweight/obese infants between 6 and 24 months. Although there is already an environment that predisposes for a subsequent pro-inflammatory response, neuroendocrine secretion changes that permit the control of the inflammatory process in this age interval can be observed. PMID:27907172

  7. Obesity and inflammatory biomarkers in women with polycystic ovary syndrome.

    PubMed

    Shen, Szu-Hung; Shen, Szu-Yu; Liou, Tsan-Hon; Hsu, Ming-I; Chang, Yuan-chin Ivan; Cheng, Chih-Yu; Hsu, Chun-Sen; Tzeng, Chii-Ruey

    2015-09-01

    To evaluate the roles of obesity and inflammatory biomarkers associated with medical complications in women with PCOS. Retrospective, BMI-matched study. A total of 330 patients, including 165 women with PCOS and 165 women without PCOS, were evaluated. The insulin resistance (homeostasis model assessment insulin resistance index - HOMA) and lipid profiles were assessed. The adiponectin, leptin, ghrelin, resistin, anti-müllerian hormone (AMH), sex hormone-binding globulin (SHBG), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) levels were also measured. Women with PCOS had significantly higher AMH, fasting insulin, total cholesterol, and low-density lipoprotein levels and lower SHBG levels compared with the controls. There was no difference in the serum obesity and inflammatory biomarkers between the PCOS cases and the controls. After adjusting for BMI and age, IL-6 was positively correlated with HOMA, and SHBG was negatively correlated with HOMA, triglyceride, and LDL. The serum adipokines levels are not good markers for PCOS. PCOS patients were characterized by their high AMH and low SHBG levels. A low level of SHBG should play an important role in the pathogenesis of the medical complications observed in women with PCOS. Clinical trial registration number NCT01989039. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Pro-inflammatory exoprotein characterization of toxic shock syndrome Staphylococcus aureus†

    PubMed Central

    Lin, Ying-Chi; Anderson, Michele J.; Kohler, Petra L.; Strandberg, Kristi L.; Olson, Michael E.; Horswill, Alexander R.; Schlievert, Patrick M.; Peterson, Marnie L.

    2011-01-01

    Pulsed-field gel electrophoresis (PFGE) clonal type USA200 is the most widely disseminated Staphylococcus aureus colonizer of the nose and is a major cause of toxic shock syndrome (TSS). Exoproteins derived from these organisms have been suggested to contribute to their colonization and causation of human diseases, but have not been well-characterized. Two representative S. aureus USA200 isolates, MNPE (α-toxin positive) and CDC587 (α-toxin mutant), isolated from pulmonary post-influenza TSS and menstrual vaginal TSS, respectively, were evaluated. Biochemical, immunobiological and cell-based assays, including mass spectrometry, were used to identify key exoproteins derived from the strains that are responsible for pro-inflammatory and cytotoxic activity on human vaginal epithelial cells. Exoproteins associated with virulence were produced by both strains, and cytolysins (α-toxin and γ-toxin), superantigens, and proteases were identified as the major exoproteins, which caused epithelial cell inflammation and cytotoxicity. Exoprotein fractions from MNPE were more pro-inflammatory and cytotoxic than those from CDC587 due to high concentrations of α-toxin. CDC587 produced a small amount of α-toxin, despite the presence of a stop codon (TAG) at codon 113. Additional exotoxin identification studies of USA200 strain [S. aureus MN8 (α-toxin mutant)] confirmed that MN8 also produced low levels of α-toxin despite the same stop codon. The differences observed in virulence factor profiles of two USA200 strains provide insight into environmental factors that select for specific virulence factors. Cytolysins, superantigens, and proteases were identified as potential targets, where toxin neutralization may prevent or diminish epithelial damage associated with S. aureus. PMID:21749039

  9. Investigation of the inflammatory biomarkers of metabolic syndrome in adolescents.

    PubMed

    Can, Ummugulsum; Buyukinan, Muammer; Guzelant, Asuman; Ugur, Ayse; Karaibrahimoglu, Adnan; Yabancıun, Sukrıye

    2016-11-01

    Metabolic syndrome (MetS) is a chronic and multifactorial syndrome characterized by a low-grade chronic inflammation, and a major risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In our study, we aimed to investigate the serum levels of high sensitive C-reactive protein (hs-CRP), haptoglobin (Hp), α2-macroglobulin (α2-MG), platelet factor-4 (PF-4), fetuin-A, serum amyloid P (SAP) and α1-acid glycoprotein (AGP) in an adolescent population with MetS. This study was performed in 43 (18 males, 25 females) MetS adolescents between the ages of 13 and 17 years (14.70±1.15) and 43 lean controls were matched for age and sex. The serum levels of Hp, α2-MG, PF-4, fetuin-A, SAP and AGP were measured by using a multi-ELISA technique. Serum Hp, fetuin-A (p<0.01) and PF-4, hs-CRP, SAP, AGP (p<0.001) values of the MetS subjects were significantly higher than those of the controls. No difference was found in serum α2-MG levels between the MetS and control groups (p=0.184). This finding suggests the possibility of using these markers in diagnosis of MetS in adolescents to prevent future complications.

  10. POEMS Syndrome in a Juvenile Initially Diagnosed as Treatment Resistant Chronic Inflammatory Demyelinating Polyneuropathy.

    PubMed

    Krish, Sonia N; Nguyen, Thy; Biliciler, Suur; Kumaravel, Manickam; Wahed, Amer; Risin, Semyon; Sheikh, Kazim A

    2015-12-01

    POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a disorder that mainly affects adults. We report a pediatric patient, initially considered to have Guillain-Barré syndrome, who continued to have progression of neuropathic disease leading to the diagnosis of chronic inflammatory demyelinating polyneuropathy. Diagnosis of POEMS was established by an abnormal bone marrow biopsy, prompted by laboratory and imaging findings, which became abnormal later in the course of the disease. POEMS syndrome is extremely rare in children, and neuropathic features in this age group have not been previously described. This case illustrates that "Guillain-Barré syndrome-like" initial presentation for POEMS, which has not been previously reported. It also emphasizes that in children with progressive acquired neuropathies that are treatment unresponsive, POEMS syndrome should be considered.

  11. [The sick building syndrome as a part of 'ASIA' (autoimmune/auto-inflammatory syndrome induced by adjuvants)].

    PubMed

    Maoz-Segal, Ramit; Agmon-Levin, Nancy; Israeli, Eitan; Shoenfeld, Yehuda

    2015-02-01

    The entity 'sick building syndrome' is poorly defined and comprises of a set of symptoms resulting from environmental exposure to a work or a living environment. The symptoms are mainly "allergic"-like and include nasal, eye, and mucous membrane irritation, dry skin as well as respiratory symptoms and general symptoms such as fatigue, lethargy, headaches and fever. The Autoimmune [Auto-inflammatory] Syndrome Induced by Adjuvants (ASIA) is a wider term which describes the role of various environmental factors in the pathogenesis of immune mediated diseases. Factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were found in association with defined and non-defined immune mediated diseases. The sick building syndrome and ASIA share a similar complex of signs and symptoms and probably the same immunological mechanisms which further support a common denominator.

  12. Deep vein thrombosis and systemic inflammatory response: a pilot trial.

    PubMed

    Reiter, Markus; Bucek, Robert A; Koca, Nihat; Dirisamer, Albert; Minar, Erich

    2003-02-28

    Symptoms of deep vein thrombosis as swelling, erythema, pain and calor have been suspected of being caused by an inflammatory reaction of the affected leg. We therefore performed a prospective pilot trial to study a possible systemic inflammatory response induced by deep vein thrombosis. We determined white blood cell count and plasma C-reactive protein in 100 consecutive patients with suspected deep vein thrombosis. The final diagnosis was based on the results of duplex sonography or ascending venography. Deep vein thrombosis was diagnosed in 37 patients (37%). White blood cell count (P = 0.012) and plasma C-reactive protein values (P < 0.001) were significantly increased in patients suffering from deep vein thrombosis. There was no correlation of white blood cell count or C-reactive protein with the thrombotic burden or the duration of symptoms. In patients with deep vein thrombosis, thrombus formation and consequent vein wall damage induce a systemic inflammatory reaction which is reflected by significantly increased levels of white blood cells and plasma C-reactive protein.

  13. A Propensity Score-Matched Analysis of Inflammatory Response With Endovascular Aneurysm Sealing vs Endovascular Aneurysm Repair.

    PubMed

    Berg, Patrick; Stroetges, Roland A; Miller, Larry E; Schoefferle, Jochen

    2017-10-01

    To evaluate the risk of postimplantation syndrome associated with endovascular aneurysm sealing (EVAS) and endovascular aneurysm repair (EVAR) in patients treated for abdominal aortic aneurysm (AAA). From December 2013 to May 2015, 41 AAA patients treated with EVAS (mean age 72±9 years; 38 men) and 63 with EVAR (mean age 74±10 years; 55 men) at a single center were retrospectively reviewed. To control for treatment selection bias, propensity score matching was used to compare outcomes by treatment mode. Main outcomes were postimplantation syndrome (defined as temperature >38°C and leukocyte count >12,000/µL), inflammatory response markers [platelets and high-sensitivity C-reactive protein (hs-CRP)], and clinical complications through 30 days. In 39 matched patients per group, the incidences of postimplantation syndrome (p=0.07), mean body temperature (p=0.05), mean leukocyte count (p=0.003), and mean hs-CRP (p<0.001) were proportionally lower with EVAS vs EVAR. Serious adverse events (0% vs 12.8%, p=0.05) and endoleaks (0% vs 10.3%, p=0.13) through 30 days were less frequent with EVAS, but the group differences were not significantly different. The choice of endovascular graft material influenced postoperative and 30-day clinical outcomes, with greater overall risk observed with polyester stent-grafts. Endovascular aneurysm sealing is associated with a blunted systematic inflammatory response compared with EVAR. Polyester stent-grafts induce the greatest periprocedural inflammatory response.

  14. Experimental heatstroke in baboon: analysis of the systemic inflammatory response.

    PubMed

    Bouchama, Abderrezak; Ollivier, Véronique; Roberts, George; Al Mohanna, Falah; de Prost, Dominique; Eldali, Abdelmoneim; Saussereau, Elodie; El-Sayed, Raafat; Chollet-Martin, Sylvie

    2005-10-01

    The objective of this study was to analyze the pattern of the inflammatory response to heatstroke in an experimental baboon model with a view to identifying potential target for therapeutic interventions. Blinded analysis of plasma collected from 12 juvenile baboons (Papio hamadryas) in heatstroke was used. Eight anesthetized animals were heat-stressed in an incubator at 44 degrees C to 47 degrees C until rectal temperature was 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. We performed sequential measurement of cytokines. The rectal temperature on completion of heat stress was 42.5 degrees C +/- 0.0 degrees C and 43.3 degrees C +/- 0.1 degrees C in moderate and severe heatstroke, respectively. Heat stress elicited early, simultaneous release of anti-inflammatory cytokines and chemokines (IL-10, IL-1ra, sTNFr I and II, and IL-8). Circulating levels of IL-12p40 were significantly decreased, whereas TNFalpha, IL-1beta, and IL-4 were below the detection limit in all animals. No baboon survived severe heatstroke; there was neurological morbidity without mortality in moderate heatstroke. Nonsurvivors displayed significantly greater activity/alterations in inflammation markers than survivors. Sham-heated animals had no evidence of inflammation activation. These results show that heatstroke activates complex systemic inflammatory and regulatory responses associated with outcome. Further definition of this ambivalent response is needed before identification of target of successful modulation may become possible.

  15. Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Chan, Y-C; Allen, D C; Fialho, D; Mills, K R; Hughes, R A C

    2006-01-01

    To discover whether Inflammatory Neuropathy Cause and Treatment Group (INCAT) electrophysiological criteria for demyelinating neuropathy predict response to immunotherapy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This was a retrospective case note study of patients who had attended Guy's Hospital Peripheral Nerve Clinic between January 2001 and March 2004, been diagnosed as having CIDP, and given treatment with corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange (PE). Patients' nerve conduction studies (NCS) were reviewed for evidence of demyelination and whether the abnormalities fulfilled modified INCAT electrophysiological criteria. Patients whose NCS fulfilled the criteria were assigned to the neurophysiologically definite CIDP group, while those that did not were labelled as neurophysiologically probable CIDP. Responses to any of the three immunotherapy agents were compared between the two groups. Out of 50 patients, 27 (54%) were classified as neurophysiologically definite and 23 (46%) as neurophysiologically probable CIDP patients. Twenty (74%) neurophysiologically definite and 17 (73.9%) neurophysiologically probable CIDP patients responded to treatment. INCAT electrophysiological criteria did not predict a higher rate of response to immunotherapy. Neurophysiologically probable CIDP patients should be given a trial of immunotherapy.

  16. Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy

    PubMed Central

    Chan, Y‐C; Allen, D C; Fialho, D; Mills, K R; Hughes, R A C

    2006-01-01

    Objective To discover whether Inflammatory Neuropathy Cause and Treatment Group (INCAT) electrophysiological criteria for demyelinating neuropathy predict response to immunotherapy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods This was a retrospective case note study of patients who had attended Guy's Hospital Peripheral Nerve Clinic between January 2001 and March 2004, been diagnosed as having CIDP, and given treatment with corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange (PE). Patients' nerve conduction studies (NCS) were reviewed for evidence of demyelination and whether the abnormalities fulfilled modified INCAT electrophysiological criteria. Patients whose NCS fulfilled the criteria were assigned to the neurophysiologically definite CIDP group, while those that did not were labelled as neurophysiologically probable CIDP. Responses to any of the three immunotherapy agents were compared between the two groups. Results Out of 50 patients, 27 (54%) were classified as neurophysiologically definite and 23 (46%) as neurophysiologically probable CIDP patients. Twenty (74%) neurophysiologically definite and 17 (73.9%) neurophysiologically probable CIDP patients responded to treatment. Conclusions INCAT electrophysiological criteria did not predict a higher rate of response to immunotherapy. Neurophysiologically probable CIDP patients should be given a trial of immunotherapy. PMID:16361609

  17. Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

    PubMed Central

    Sung, Nak Yoon

    2015-01-01

    Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation. PMID:26330757

  18. Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis

    PubMed Central

    Lu, Ching-Hua; Allen, Kezia; Oei, Felicia; Leoni, Emanuela; Kuhle, Jens; Tree, Timothy; Fratta, Pietro; Sharma, Nikhil; Sidle, Katie; Howard, Robin; Orrell, Richard; Fish, Mark; Greensmith, Linda; Pearce, Neil; Gallo, Valentina

    2016-01-01

    Objective: To evaluate the combined blood expression of neuromuscular and inflammatory biomarkers as predictors of disease progression and prognosis in amyotrophic lateral sclerosis (ALS). Methods: Logistic regression adjusted for markers of the systemic inflammatory state and principal component analysis were carried out on plasma levels of creatine kinase (CK), ferritin, and 11 cytokines measured in 95 patients with ALS and 88 healthy controls. Levels of circulating biomarkers were used to study survival by Cox regression analysis and correlated with disease progression and neurofilament light chain (NfL) levels available from a previous study. Cytokines expression was also tested in blood samples longitudinally collected for up to 4 years from 59 patients with ALS. Results: Significantly higher levels of CK, ferritin, tumor necrosis factor (TNF)–α, and interleukin (IL)–1β, IL-2, IL-8, IL-12p70, IL-4, IL-5, IL-10, and IL-13 and lower levels of interferon (IFN)–γ were found in plasma samples from patients with ALS compared to controls. IL-6, TNF-α, and IFN-γ were the most highly regulated markers when all explanatory variables were jointly analyzed. High ferritin and IL-2 levels were predictors of poor survival. IL-5 levels were positively correlated with CK, as was TNF-α with NfL. IL-6 was strongly associated with CRP levels and was the only marker showing increasing expression towards end-stage disease in the longitudinal analysis. Conclusions: Neuromuscular pathology in ALS involves the systemic regulation of inflammatory markers mostly active on T-cell immune responses. Disease stratification based on the prognostic value of circulating inflammatory markers could improve clinical trials design in ALS. PMID:27308305

  19. Microparticles: Inflammatory and haemostatic biomarkers in Polycystic Ovary Syndrome.

    PubMed

    Carvalho, L M L; Ferreira, C N; Sóter, M O; Sales, M F; Rodrigues, K F; Martins, S R; Candido, A L; Reis, F M; Silva, I F O; Campos, F M F; Gomes, K B

    2017-03-05

    Polycystic Ovary Syndrome (PCOS) is associated with a chronic low-grade inflammation and predisposition to hemostatic and atherosclerotic complications. This case-control study evaluated the microparticles (MPs) profile in patients with the PCOS and related these MPs to clinical and biochemical parameters. MPs derived from platelets (PMPs), leuckocytes (LMPs) and endothelial cells (EMPs) were evaluated, as well as MPs expressing tissue factor (TFMPs), by flow cytometry, comparing women with PCOS (n = 50) and a healthy control group (n = 50). PCOS women presented increased total MPs, PMPs, LMPs and EMPs levels when compared to control group (all p < 0.05). TFMPs was similar between the groups (p = 0.379). In conclusion, these MPs populations could be useful biomarkers for association with thrombosis and cardiovascular disease in PCOS women.

  20. Short communication: Camel milk ameliorates inflammatory responses and oxidative stress and downregulates mitogen-activated protein kinase signaling pathways in lipopolysaccharide-induced acute respiratory distress syndrome in rats.

    PubMed

    Zhu, Wei-Wei; Kong, Gui-Qing; Ma, Ming-Ming; Li, Yan; Huang, Xiao; Wang, Li-Peng; Peng, Zhen-Yi; Zhang, Xiao-Hua; Liu, Xiang-Yong; Wang, Xiao-Zhi

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is a complex syndrome disorder with high mortality rate. Camel milk (CM) contains antiinflammatory and antioxidant properties and protects against numerous diseases. This study aimed to demonstrate the function of CM in lipopolysaccharide (LPS)-induced ARDS in rats. Camel milk reduced the lung wet:dry weight ratio and significantly reduced LPS-induced increases in neutrophil infiltration, interstitial and intra-alveolar edema, thickness of the alveolar wall, and lung injury scores of lung tissues. It also had antiinflammatory and antioxidant effects on LPS-induced ARDS. After LPS stimulation, the levels of proinflammatory cytokines (tumor necrosis factor-α, IL-10, and IL-1β) in serum and oxidative stress markers (malondialdehyde, myeloperoxidase, and total antioxidant capacity) in lung tissue were notably attenuated by CM. Camel milk also downregulated mitogen-activated protein kinase signaling pathways. Given these results, CM is a potential complementary food for ARDS treatment.

  1. Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

    PubMed

    Zhong, Franklin L; Mamaï, Ons; Sborgi, Lorenzo; Boussofara, Lobna; Hopkins, Richard; Robinson, Kim; Szeverényi, Ildikó; Takeichi, Takuya; Balaji, Reshmaa; Lau, Aristotle; Tye, Hazel; Roy, Keya; Bonnard, Carine; Ahl, Patricia J; Jones, Leigh Ann; Baker, Paul; Lacina, Lukas; Otsuka, Atsushi; Fournie, Pierre R; Malecaze, François; Lane, E Birgitte; Akiyama, Masashi; Kabashima, Kenji; Connolly, John E; Masters, Seth L; Soler, Vincent J; Omar, Salma Samir; McGrath, John A; Nedelcu, Roxana; Gribaa, Moez; Denguezli, Mohamed; Saad, Ali; Hiller, Sebastian; Reversade, Bruno

    2016-09-22

    Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

  2. Expression of pro-inflammatory TACE-TNF-α-amphiregulin axis in Sjögren's syndrome salivary glands.

    PubMed

    Sisto, Margherita; Lisi, Sabrina; Lofrumento, Dario Domenico; Ingravallo, Giuseppe; Mitolo, Vincenzo; D'Amore, Massimo

    2010-10-01

    The tumor-necrosis-factor-converting-enzyme (TACE)-TNF-α-Amphiregulin (AREG) axis plays an important pathogenic role in inflammatory and autoimmune disorders. However, the pathological roles of these proteins in the chronic autoimmune disease Sjögren's syndrome (SS) remain to be elucidated. It is known that the TACE-AREG axis is clearly part of a larger cascade of signals that starts with the activation of Furin, responsible for maturation of TACE that, in turn, determines the production of active TNF-α, directly involved in the up-regulation of AREG expression. This study showed that Furin, TACE, TNF-α, and AREG proteins, detected in acinar and ductal cells of human salivary glands from SS patients, increased remarkably in comparison with biopsies of labial salivary glands from healthy controls. The changes in Furin, TACE, TNF- α, and AREG proteins' level detected in salivary glands biopsies of SS patients could be responsible for pro-inflammatory cytokines overexpression characterizing Sjögren's syndrome.

  3. Metabolic syndrome and inflammatory biomarkers: a community-based cross-sectional study at the Framingham Heart Study

    PubMed Central

    2012-01-01

    Background Prior studies reported conflicting findings on the association between metabolic syndrome and inflammatory biomarkers. We tested the cross-sectional associations between metabolic syndrome and nine inflammatory markers. Methods We measured C-reactive protein, CD40 ligand, interleukin-6, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, tumor necrosis factor-alpha, and tumor necrosis factor receptor-2 in 2570 Framingham Offspring Study participants free of diabetes and cardiovascular disease at examination 7. Metabolic syndrome was defined by National Cholesterol Education Program criteria. We performed multivariable linear regressions for each biomarker with metabolic syndrome as the exposure adjusting for age, sex, smoking, aspirin use, and hormone replacement. We subsequently added to the models components of the metabolic syndrome as continuous traits plus lipid lowering and hypertension treatments. We considered P < 0.05 as statistically significant. Results Metabolic syndrome was present in 984 (38%) participants and was statistically significantly associated with each biomarker (all P < 0.02) except osteoprotegerin. After adjusting for its component variables, the metabolic syndrome was associated only with P-selectin (1.06 fold higher in metabolic syndrome, 95% CI 1.02, 1.10, p = 0.005). Conclusions Metabolic syndrome was associated with multiple inflammatory biomarkers. However, adjusting for each of its components eliminated the association with most inflammatory markers, except P-selectin. Our results suggest that the relation between metabolic syndrome and inflammation is largely accounted for by its components. PMID:22716219

  4. Antibodies against a Surface Protein of Streptococcus pyogenes Promote a Pathological Inflammatory Response

    PubMed Central

    Kahn, Fredrik; Mörgelin, Matthias; Shannon, Oonagh; Norrby-Teglund, Anna; Herwald, Heiko; Olin, Anders I.; Björck, Lars

    2008-01-01

    Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein–induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein–fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response. PMID:18787689

  5. Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage.

    PubMed

    Naredi, Silvana; Lambert, Gavin; Friberg, Peter; Zäll, Stefan; Edén, Elisabeth; Rydenhag, Bertil; Tylman, Maria; Bengtsson, Anders

    2006-12-01

    The aim of this study was to evaluate the correlation between sympathetic nervous activation and the immune response in patients following subarachnoid haemorrhage (SAH). Clinical study in a neurosurgical intensive care unit. Fourteen patients with acute non-traumatic SAH were included. Fifteen healthy, age-matched volunteers served as controls for measurement of catecholamine spillover. Blood sampling for C3a, C5b-9, IL-6, IL-8 and norepinephrine kinetic determination was made within 48 h, at 72 h and on the 7th-10th day after the SAH. SAH patients exhibited a profound increase in the rate of norepinephrine spillover to plasma at 48 h, 72 h and 7-10 days after the insult, 3-4 times that in healthy individuals. The plasma levels of C3a, IL-6 and C5b-9 were significantly elevated at 48 h, at 72 h and 7-10 days after the SAH, but the plasma level of IL-6 decreased significantly 7-10 days after the SAH. There was no relationship between the magnitude of sympathetic activation and the levels of inflammatory markers. Following SAH a pronounced activation of the sympathetic nervous system and the inflammatory system occurs. The lack of significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and the immune response, following SAH are not quantitatively linked. In spite of a persistent high level of sympathetic activation the plasma level of IL-6 decreased significantly one week after SAH.

  6. Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis

    PubMed Central

    Segura-Cervantes, Enrique; Mancilla-Ramírez, Javier; González-Canudas, Jorge; Alba, Erika; Santillán-Ballesteros, René; Morales-Barquet, Deneb; Sandoval-Plata, Gabriela

    2016-01-01

    The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation. PMID:27293317

  7. Renal inflammatory response to urinary tract infection in rat neonates.

    PubMed

    Zarepour, M; Moradpoor, H; Emamghorashi, F; Owji, S M; Roodaki, M; Khamoushi, M

    2015-09-01

    Urinary tract infection (UTI) is one of the most common bacterial infections. Maternal UTI is a risk factor for neonatal UTI. The aim of the present study was to determine the severity of renal inflammation in neonate rats born from mothers with induced UTI. Twelve pregnant rats (Sprague-Dawley) were included in study. The rats were divided into two groups (six rats in each group). In the first group, pyelonephritis was induced in the third trimester of pregnancy and the second group was used as a control group. After delivery, the neonates were divided into three groups based on days after birth (the 1 st, 3 rd and 7 th days after birth). In each group, two neonates of each mother were killed and a midline abdominal incision was made and both kidneys were aseptically removed. On the 7 th day, rat mothers were killed and their kidneys were removed. The preparations were evaluated with a bright field microscope for inflammatory response. Renal pathology showed inflammation in all UTI-induced mothers, but only two cases of neonates (2.1%) showed inflammation in the renal parenchyma. There was no relation between the positive renal culture and the pathological changes. We conclude that neonates with UTI born to UTI-induced mothers showed a lesser inflammatory response.

  8. Ovalbumin Sensitization Changes the Inflammatory Response to Subsequent Parainfluenza Infection

    PubMed Central

    Adamko, Darryl J.; Yost, Bethany L.; Gleich, Gerald J.; Fryer, Allison D.; Jacoby, David B.

    1999-01-01

    Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia. This may reflect altered inflammatory response to viruses in atopic individuals. Inhibitory M2 muscarinic receptors (M2Rs) on the airway parasympathetic nerves limit acetylcholine release. Both viral infection and inhalational antigen challenge cause M2R dysfunction, leading to airway hyperresponsiveness. In antigen-challenged, but not virus-infected guinea pigs, M2R dysfunction is due to blockade of the receptors by the endogenous antagonist eosinophil major basic protein (MBP). We hypothesized that sensitization to a nonviral antigen before viral infection alters the inflammatory response to viral infection, so that M2R dysfunction and hyperreactivity are eosinophil mediated. Guinea pigs were sensitized to ovalbumin intraperitoneally, and 3 wk later were infected with parainfluenza. In sensitized, but not in nonsensitized animals, virus-induced hyperresponsiveness and M2R dysfunction were blocked by depletion of eosinophils with antibody to interleukin (IL)-5 or treatment with antibody to MBP. An additional and unexpected finding was that sensitization to ovalbumin caused a marked (80%) reduction in the viral content of the lungs. This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity. PMID:10562321

  9. A MATHEMATICAL SIMULATION OF THE INFLAMMATORY RESPONSE TO ANTHRAX INFECTION

    PubMed Central

    Kumar, Rukmini; Chow, Carson C.; Bartels, John D.; Clermont, Gilles; Vodovotz, Yoram

    2013-01-01

    Bacillus anthracis (anthrax) can trigger an acute inflammatory response that results in multisystem organ failure and death. Previously, we developed a mathematical model of acute inflammation after gram-negative infection that had been matched qualitatively to literature data. We modified the properties of the invading bacteria in that model to those specific to B. anthracis and simulated the host response to anthrax infection. We simulated treatment strategies against anthrax in a genetically diverse population including the following: (1) antibiotic treatment initiated at various time points, (2) antiprotective antigen vaccine, and (3) a combination of antibiotics and vaccine. In agreement with studies in mice, our simulations showed that antibiotics only improve survival if administered early in the course of anthrax infection. Vaccination that leads to the formation of antibodies to protective antigen is anti-inflammatory and beneficial in averting shock and improving survival. However, antibodies to protective antigen alone are predicted not to be universally protective against anthrax infection. Rather, our simulations suggest that an optimal strategy would require both vaccination and antibiotic administration. PMID:18157069

  10. Characterisation of the local inflammatory response in appendicitis.

    PubMed

    Tsuji, M; Puri, P; Reen, D J

    1993-01-01

    In this study we have characterised the local inflammatory response in acute suppurative appendicitis (S), focal appendicitis (F), and normal appendices (C). Enumeration of lymphocyte subpopulations, cells expressing IL-2 receptor, natural killer (NK) cells, monocytes and plasma cell isotypes and subclasses infiltrating the lamina propria was carried out on all specimens using immunoperoxidase staining procedures. Total T cells were significantly increased in both acute suppurative appendicitis and focal appendicitis compared with controls (p < 0.001). Cells infiltrating the lamina propria expressed IL-2 receptor in all appendiceal specimens but were significantly increased in both acute and focal appendicitis (p < 0.01). IgG and IgA plasma cell isotypes were significantly increased in all S and F appendiceal specimens (p < 0.001). Monocyte and NK cell numbers, however, were only increased in acute suppurative appendiceal specimens. The increased lymphocyte and plasma cell isotypes seen in focal appendicitis occurred throughout the entire organ even through the inflammatory focus was confined to only three to seven serial sections. These results clearly show a differential pattern of cellular infiltration in focal appendicitis from that seen in acute suppurative appendicitis. The selective lymphocyte and plasma cell nature of the cellular infiltrate in the lamina propria of focal appendicitis may reflect the presence of a specific immune response to an as yet unidentified luminal antigen as a possible cause of appendicitis.

  11. SIGIRR modulates the inflammatory response in the brain.

    PubMed

    Watson, Melanie B; Costello, Derek A; Carney, Dónal G; McQuillan, Keith; Lynch, Marina A

    2010-08-01

    One of the more recently described members of the interleukin-1 (IL-1) receptor family, single-Ig-interleukin-1 related receptor (SIGIRR), has been identified as a negative regulator of inflammation in several tissues. It modulates the responses triggered by stimulation of Toll-like receptor (TLR) 4 and IL-1 in several peripheral cell types, possibly in an NFkappaB-dependent manner. Consistently, responses to lipopolysaccharide (LPS) are exaggerated in SIGIRR-deficient mice and the symptoms of experimental inflammatory conditions are more profound in these animals. Here, we set out to establish whether the absence of SIGIRR was associated with inflammatory changes in the brain and report that, LPS-induced a greater effect on CD40 and ICAM mRNA in mixed glia prepared from SIGIRR(-/-), compared with wildtype mice. This was associated with parallel changes in TNFalpha and IL-6 at mRNA and protein levels, an effect which was observed in purified microglia but not astrocytes. Similarly, LPS exerted a more profound effect on microglial activation and cytokine production in hippocampal tissue prepared from SIGIRR(-/-), compared with wildtype mice. The effect of LPS on exploratory behaviour was also accentuated in SIGIRR(-/-) mice. The evidence suggests that these changes are a likely consequence of increased hippocampal expression of CD14 and TLR4, and NFkappaB activation in SIGIRR(-/-) mice. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Inflammatory and bone remodeling responses to the cytolethal distending toxins.

    PubMed

    Belibasakis, Georgios N; Bostanci, Nagihan

    2014-04-04

    The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  13. Associations among Metabolic Syndrome, Ischemia, Inflammatory, Oxidatives, and Lipids Biomarkers

    PubMed Central

    Valle Gottlieb, Maria Gabriela; da Cruz, Ivana Beatrice Mânica; Duarte, Marta M. F.; Moresco, Rafael Noal; Wiehe, Mário; Schwanke, Carla Helena Augustin; Bodanese, Luiz Carlos

    2010-01-01

    Context: Metabolic syndrome (MS) is described as a cluster of cardiometabolic risk factors. Studies suggest that ischemia-modified albumin (IMA) is a biomarker of cardiovascular diseases. IMA levels could be associated with cardiometabolic risks and represent a possible indication of microvascular dysfunction in MS patients. Objective: To confirm this possible association, we evaluated the association between IMA levels and MS. Design: We performed a case-control study (32 healthy individuals and 74 subjects with MS) to evaluate the association between MS, IMA, and other biomarkers [high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (OxLDL), oxidized low-density lipoprotein autoantibodies (anti-OxLDL), IL-6, lipid profile, and glucose]. Results: The MS group showed higher levels of IMA (0.618 ± 0.1355) as well as higher levels of hs-CRP, OxLDL, anti-OxLDL, and IL-6 than did control subjects (IMA = 0.338 ± 0.0486) (P < 0.01). Multivariate analysis showed that IMA and MS association was independent of sex, age, diabetes mellitus 2, and hypercholesterolemia. Conclusion: We found an association between IMA and MS. Additional studies including prospective genetic variation approaches need to be performed to help elucidate this association between IMA and MS and its potential clinical role. PMID:20016051

  14. Response to infliximab in SAPHO syndrome

    PubMed Central

    Fruehauf, Julia; Cierny-Modrè, Brigitte; Caelen, Laila El-Shabrawi; Schwarz, Thomas; Weinke, Roland; Aberer, Elisabeth

    2009-01-01

    Infliximab has become increasingly important in the treatment of SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. There is, however, little experience with this biological agent, and treatment protocols usually follow the regimens for spondylarthropathies. We report a patient with a highly unusual and severe clinical presentation of SAPHO syndrome including widespread bone and skin disease, and collagenous colitis. Infliximab treatment (5 mg/kg) given at weeks 0, 2 and 6 and every 8 weeks thereafter, induced rapid remission of the osteoarticular symptoms, although the skin lesions improved only partially, and after 10 months continuous therapy with infliximab a bone scan even uncovered new active bone lesions. Collagenous colitis is unresponsive to tumour necrosis factor α (TNFα) blocking agents. This moderate response to infliximab may indicate that a more aggressive treatment protocol is mandatory. We further believe that remission of osteoarticular complaints should be routinely confirmed by scintigraphic findings to verify treatment response. PMID:21686446

  15. [Target Molecule for a Demyelinating Type of Guillain-Barré Syndrome, Acute Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Mori, Masahiro

    2015-11-01

    Guillain-Barré syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP.

  16. Immune reconstitution inflammatory syndrome, human herpesvirus 8 viremia, and HIV-associated multicentric Castleman disease.

    PubMed

    Siegel, Marc O; Ghafouri, Sanaz; Ajmera, Ravi; Simon, Gary L

    2016-07-01

    Kaposi's sarcoma and multicentric Castleman Disease are HIV-related disease processes that are associated with human herpesvirus 8 (HHV-8) infection. The development of multicentric Castleman disease can often be a manifestation of the immune reconstitution inflammatory syndrome phenomenon and is associated with markedly elevated levels of HHV-8 viremia, as illustrated by this case. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Quantitative Risk-Benefit Analysis of Probiotic Use for Irritable Bowel Syndrome and Inflammatory Bowel Disease.

    PubMed

    Bennett, William E

    2016-04-01

    Probiotics have seen widespread use for a variety of gastrointestinal problems, especially in two common disorders: irritable bowel syndrome and inflammatory bowel disease. Since a wide variety of probiotic preparations has been used, and despite a large number of studies performed, a great deal of heterogeneity exists among them. Straightforward evidence-based recommendations for the use of probiotics in irritable bowel syndrome and inflammatory bowel disease have thus been difficult to formulate. In an effort to improve understanding of the risk-benefit balance of probiotics in these conditions, this study (1) queried the US FDA Adverse Event Reporting System (FAERS) database for all reported adverse drug events related to probiotics in 2013, and (2) constructed risk-benefit planes for both irritable bowel syndrome and inflammatory bowel disease using a geometric approximation of the confidence region between risk and benefit. The results show that adverse events from probiotics vary widely by disease, and when they occur, they are mild and may be difficult to distinguish from the natural history of the underlying disorders they are used to treat. The risk-benefit plane for irritable bowel syndrome straddles the risk-benefit threshold, so patients can expect a balance between a low chance of risk and also a low chance of benefit. The risk-benefit plane for inflammatory bowel disease largely lies above the risk-benefit threshold, so patients may expect more benefit than risk in most cases. More standardized and high-quality research is needed to improve our understanding of risk and benefit for these complex biopharmaceuticals.

  18. Innate immune response to pulmonary contusion: Identification of cell-type specific inflammatory responses

    PubMed Central

    Hoth, J. Jason; Wells, Jonathan D.; Yoza, Barbara K.; McCall, Charles E.

    2012-01-01

    Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow (BM) transfer between TLR2−/− or TLR4−/− and wild-type (WT) mice. We found that in the lung, both BM-derived and non-myeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type specific manner. We also show a novel TLR2 dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion. PMID:22293596

  19. Innate immune response to pulmonary contusion: identification of cell type-specific inflammatory responses.

    PubMed

    Hoth, J Jason; Wells, Jonathan D; Yoza, Barbara K; McCall, Charles E

    2012-04-01

    Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow transfer between TLR2 or TLR4 and wild-type mice. We found that, in the lung, both bone marrow-derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type-specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type-specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion.

  20. Topical Modulation of the Burn Wound Inflammatory Response to Improve Short and Long Term Outcomes

    DTIC Science & Technology

    2015-10-15

    between p38MAPK signaling, wound inflammatory response, wound healing and long-term scar formation using a burn model in the female red Duroc pig...inflammatory phase of wound healing , and decrease the granulation layer thickness. We propose this modification in the early inflammatory response will also...brief list of keywords (limit to 20 words). Wounds , Burn, topical, wound healing , inflammatory signaling, Mitogen activated protein kinase

  1. Topical Modulation of the Burn Wound Inflammatory Response to Improve Short and Long Term Outcomes

    DTIC Science & Technology

    2015-10-01

    between p38MAPK signaling, wound inflammatory response, wound healing and long-term scar formation using a burn model in the female red Duroc pig...inflammatory phase of wound healing , and decrease the granulation layer thickness. We propose this modification in the early inflammatory response will also...brief list of keywords (limit to 20 words). Wounds , Burn, topical, wound healing , inflammatory signaling, Mitogen activated protein kinase

  2. Criminal and legal responsibilities in Tourette's syndrome.

    PubMed

    Gullucayir, Sibel; Asirdizer, Mahmut; Yavuz, M Sunay; Zeyfeoglu, Yildiray; Ulucay, Tarik

    2009-01-01

    Tourette's Syndrome (TS) is a neuropsychological disorder characterized by the presence of multiple involuntary motor tics accompanied by one or more vocal tics. Articles about TS and criminal responsibility and the restriction of civil rights are limited. A person with TS was evaluated to consider his criminal responsibility after swearing at a referee during a football game. He was also evaluated as to whether or not he was capable of professionally driving a service bus. Additionally, medico-legal situations regarding military service, obtaining a shotgun license and marriages of patients with TS were considered.

  3. Cardiovascular and inflammatory response to cholecystokinin during endotoxemic shock.

    PubMed

    Saia, Rafael Simone; Bertozi, Giuliana; Mestriner, Fabíola Leslie; Antunes-Rodrigues, José; Queiróz Cunha, Fernando; Cárnio, Evelin Capellari

    2013-01-01

    Cholecystokinin (CCK) was first described as a gastrointestinal hormone, but its receptors have been located in cardiac and vascular tissues, as well as in immune cells. Our aims were to investigate the role of CCK on lipopolysaccharide (LPS)-induced hypotension and its ability to modulate previously reported inflammatory mediators, therefore affecting cardiovascular function. To conduct these experiments, rats had their jugular vein cannulated for drug administration, and also, the femoral artery cannulated for mean arterial pressure (MAP) and heart rate records. Endotoxemia induced by LPS from Escherichia coli (1.5 mg/kg; i.v.) stimulated the release of CCK, a progressive drop in MAP, and increase in heart rate. Plasma tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), nitrate, vasopressin, and lactate levels were elevated in the endotoxemic rats. The pretreatment with proglumide (nonselective CCK antagonist; 30 mg/kg; i.p.) aggravated the hypotension and also increased plasma TNF-α and lactate levels. On the other hand, CCK (0.4 μg/kg; i.v.) administered before LPS significantly restored MAP, reduced aortic and hepatic inducible nitric oxide synthase (iNOS) production, and elevated plasma vasopressin and IL-10 concentrations; it did not affect TNF-α. Physiological CCK concentration reduced nitrite and iNOS synthesis by peritoneal macrophages, possibly through a self-regulatory IL-10-dependent mechanism. Together, these data suggest a new role for the peptide CCK in modulating MAP, possibly controlling the inflammatory response, stimulating the anti-inflammatory cytokine, IL-10, and reducing vascular and macrophage iNOS-derived nitric oxide production. Based on these findings, CCK could be used as an adjuvant therapeutic agent to improve cardiovascular function.

  4. Acute inflammatory bowel disease complicating chronic alcoholism and mimicking carcinoid syndrome.

    PubMed

    Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo

    2012-05-01

    We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

  5. Acute Inflammatory Bowel Disease Complicating Chronic Alcoholism and Mimicking Carcinoid Syndrome

    PubMed Central

    Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo

    2012-01-01

    We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome. PMID:22949895

  6. Plasma levels of inflammatory cytokines in adult Nigerians with the metabolic syndrome

    PubMed Central

    Christiana, Udenze Ifeoma; Casimir, Amadi E.; Nicholas, Awolola Awodele; Christian, Makwe C.; Obiefuna, Ajie I.

    2016-01-01

    Background: The aim of this study is to determine the plasma levels of interleukin 6 (IL-6), tumor necrotic factor alpha (TNF-α, and C-reactive protein (CRP) in adult Nigerians with the metabolic syndrome and to determine the relationship between components of the metabolic syndrome and CRP in adult Nigerians. Subjects and Methods: This was a case–control study of fifty adult men and women with the metabolic syndrome, and fifty age- and sex-matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Written informed consent was obtained from the participants. Blood pressure and anthropometry measurements were taken and venous blood was collected after an overnight fast. The Ethics Committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparisons of continuous variables and categorical variables were done using the Student's t-test and Chi-square test, respectively. Regression analysis was used to determine the associations between variables. Statistical significance was set at P< 0.05. Results: The age- and sex-matched males and females with and without the metabolic syndrome did not differ in their sociodemographic characteristics. They however differed in some clinical and laboratory parameters such as diastolic blood pressure (P = 0.048), waist circumference (P = 0.002), body mass index (P = 0.012), waist/hip ratio (P = 0.023), high density lipoprotein (HDL) (P = 0.012), and insulin resistance (IR) (P = 0.042). There was a statistically significant increase in the inflammatory marker, CRP (P = 0.019), the cytokines, IL6 (P = 0.040), and TNF-α (P = 0.031) between the subjects with and without metabolic syndrome. There was also a significant association between CRP, waist circumference, IR, and HDL in the metabolic syndrome (P < 0.05). Conclusion: Plasma levels of inflammatory cytokines are raised in

  7. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    PubMed

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  8. Biotin deficiency enhances the inflammatory response of human dendritic cells

    PubMed Central

    Agrawal, Sudhanshu; Said, Hamid M.

    2016-01-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency. PMID:27413170

  9. Biomechanical changes in endothelial cells result from an inflammatory response

    NASA Astrophysics Data System (ADS)

    Vaitkus, Janina; Stroka, Kimberly; Aranda-Espinoza, Helim

    2012-02-01

    During periods of infection and disease, the immune system induces the release of TNF-α, an inflammatory cytokine, from a variety of cell types, such as macrophages. TNF-α, while circulating in the vasculature, binds to the apical surface of endothelial cells and causes a wide range of biological and mechanical changes to the endothelium. While the biological changes have been widely studied, the biomechanical aspects have been largely unexplored. Here, we investigated the biomechanical changes of the endothelium as a function of TNF-α treatment. First, we studied the traction forces applied by the endothelium, an effect that is much less studied than others. Through the use of traction force microscopy, we found that TNF-α causes an increase in traction forces applied by the endothelial cells as compared to non-treated cells. Then, we investigated cell morphology, cell mechanics, migration, and cytoskeletal dynamics. We found that in addition to increasing applied traction forces, TNF-α causes an increase in cell area and aspect ratio on average, as well as a shift in the organization of F-actin filaments within the cell. Combining these findings together, our results show that an inflammatory response heavily impacts the morphology, cell mechanics, migration, cytoskeletal dynamics, and applied traction forces of endothelial cells.

  10. Extrinsic and intrinsic control of macrophage inflammatory responses.

    PubMed

    Cohen, Heather B; Mosser, David M

    2013-11-01

    Macrophages make major contributions to inflammatory immunopathology. In this work, we examine three disease scenarios, in which M1s play a major role early in the disease but eventually transitions into a population of cells with immunoregulatory activity. We propose that the transition from an inflammatory to a regulatory phenotype is a natural progression that regularly occurs in stimulated macrophages and that the timing of this transition is critical to maintaining homeostasis. In the first section of this review, we discuss the exogenous microenvironmental cues that may induce macrophages to enter a regulatory state. In the second half of this review, we discuss a novel mechanism, whereby TLR-stimulated macrophages can intrinsically induce their own regulatory activation state. They do so by secreting and synthesizing endogenous "reprogramming" signals that work in an autocrine fashion to promote a regulatory phenotype. We propose that these endogenous regulatory mechanisms exist to prevent macrophage-mediated immunopathology. Thus, macrophages can respond to endogenous and exogenous cues to regulate their activation state, and without these controlled regulatory responses, M1 would persist to the detriment of the host.

  11. Ozone promotes regeneration by regulating the inflammatory response in zebrafish.

    PubMed

    Hao, Kenan; Li, Yanhao; Feng, Jianyu; Zhang, Wenqing; Zhang, Yiyue; Ma, Ning; Zeng, Qingle; Pang, Huajin; Wang, Chunyan; Xiao, Lijun; He, Xiaofeng

    2015-09-01

    Ozone is thought to advance wound healing by inhibiting inflammation, but the mechanism of this phenomenon has not been determined. Although the zebrafish is often used in regeneration experiments, there has been no report of zebrafish treated with ozonated water. We successfully established a zebrafish model of ozonated water treatment and demonstrate that ozonated water stimulates the regeneration of the zebrafish caudal fin, its mechanism, and time dependence. The growth rate of the caudal fin and the number of neutrophils migrating to the caudal fin wound after resection were higher in the experimental (ozonated) group than in the control group, preliminarily confirming that ozone-promoted regeneration is related to the stimulation of an early inflammatory response by ozone. Ozone modulated the expression of tumor necrosis factor-α (TNF-α) in two ways by regulating interleukin 10 (IL-10) expression. Therefore, ozone promotes tissue regeneration by regulating the inflammatory pathways. This effect of ozone in an experimental zebrafish model is demonstrated for the first time, confirming its promotion of wound healing and the mechanism of its effect in tissue regeneration. These results will open up new directions for ozone and regeneration research.

  12. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    PubMed Central

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

  13. Local and systemic inflammatory responses to experimentally induced gingivitis.

    PubMed

    Leishman, Shaneen J; Seymour, Gregory J; Ford, Pauline J

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual.

  14. Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets

    PubMed Central

    Kim, Jong Youl; Kawabori, Masahito; Yenari, Midori A.

    2014-01-01

    Stroke is a frequent cause of long-term disability and death worldwide. Ischemic stroke is more commonly encountered compared to hemorrhagic stroke, and leads to tissue death by ischemia due to occlusion of a cerebral artery. Inflammation is known to result as a result of ischemic injury, long thought to be involved in initiating the recovery and repair process. However, work over the past few decades indicates that aspects of this inflammatory response may in fact be detrimental to stroke outcome. Acutely, inflammation appears to have a detrimental effect, and anti-inflammatory treatments have been been studied as a potential therapeutic target. Chronically, reports suggest that post-ischemic inflammation is also essential for the tissue repairing and remodeling. The majority of the work in this area has centered around innate immune mechanisms, which will be the focus of this review. This review describes the different key players in neuroinflammation and their possible detrimental and protective effects in stroke. A better understanding of the roles of the different immune cells and their temporal profile of damage versus repair will help to clarify more effective modulation of inflammation post stroke. Introduction Stroke refers to conditions caused by occlusion and/or rupture of blood vessels in the brain, and is a leading cause of death and disability in the industrialized world. PMID:24372209

  15. Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing

    PubMed Central

    Fronza, Marcio; Caetano, Guilherme F.; Leite, Marcel N.; Bitencourt, Claudia S.; Paula-Silva, Francisco W. G.; Andrade, Thiago A. M.; Frade, Marco A. C.; Merfort, Irmgard; Faccioli, Lúcia H.

    2014-01-01

    Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders. PMID:25393024

  16. High Frequency of Chronic Bacterial and Non-Inflammatory Prostatitis in Infertile Patients with Prostatitis Syndrome Plus Irritable Bowel Syndrome

    PubMed Central

    Vicari, Enzo; La Vignera, Sandro; Arcoria, Domenico; Condorelli, Rosita; Vicari, Lucia O.; Castiglione, Roberto; Mangiameli, Andrea; Calogero, Aldo E.

    2011-01-01

    Background Although prostatitis syndrome (PS) and irritable bowel syndrome (IBS) are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis. Methodology/Principal Findings This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) in an andrological setting, and 204 patients with IBS, diagnosed according to the Rome III diagnostic criteria in a gastroenterological setting. The patients with PS were asked to fulfill the Rome III questionnaire for IBS, whereas patients with IBS were asked to complete the NIH-CPSI. The simultaneous presence of PS and IBS was observed in 30.2% and 31.8% of the patients screened by andrologists and gastroenterologists, respectively. Altogether, 111 patients had PS plus IBS (31.2%). They had a total NIH-CPSI and pain subscale scores significantly higher than patients with PS alone. Gastrointestinal symptoms in patients with PS plus IBS were similar to those reported by patients with IBS alone and significantly greater in patients with PS alone. Patients with PS plus IBS had a significantly higher frequency of chronic bacterial prostatitis (category II) and lower of non-inflammatory prostatitis (category IIIB), compared to patients with PS alone. The frequency of inflammatory prostatitis (category IIIA) resulted similar. Conclusions/Significance Prostatitis syndromes and IBS are frequently associated in patients with PS- or IBS-related symptoms. These patients have an increased prevalence of chronic bacterial and non-inflammatory prostatitis. PMID:21494624

  17. Regulation of inflammatory responses by IL-17F.

    PubMed

    Yang, Xuexian O; Chang, Seon Hee; Park, Heon; Nurieva, Roza; Shah, Bhavin; Acero, Luis; Wang, Yi-Hong; Schluns, Kimberly S; Broaddus, Russell R; Zhu, Zhou; Dong, Chen

    2008-05-12

    Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor-associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F-deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

  18. Regulation of inflammatory responses by IL-17F

    PubMed Central

    Yang, Xuexian O.; Chang, Seon Hee; Park, Heon; Nurieva, Roza; Shah, Bhavin; Acero, Luis; Wang, Yi-Hong; Schluns, Kimberly S.; Broaddus, Russell R.; Zhu, Zhou; Dong, Chen

    2008-01-01

    Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases. PMID:18411338

  19. Comparison of the inflammatory response between miniaturized and standard CPB circuits in aortic valve surgery.

    PubMed

    Bical, Olivier M; Fromes, Yves; Gaillard, Didier; Fischer, Marc; Ponzio, Olivier; Deleuze, Philippe; Gerhardt, Marie-Françoise; Trivin, François

    2006-05-01

    One of the complications of CPB is the systemic inflammatory response syndrome (SIRS). Recent developments tend to minimize the biological impact of CPB in using miniaturized closed circuit with reduced priming volume and less blood-air interface. The benefit of these miniaturized closed circuits in terms of inflammatory response has been proved in coronary surgery. However, in open heart surgery, the CPB circuit is no more closed and the benefit of the miniaturized set-up could disappear. The aim of the study is to compare the SIRS between standard and miniaturized circuits in aortic surgery. Forty patients who underwent singular aortic valve replacement were randomly assigned either to a standard CPB (group A, n=20) or to a miniaturized CPB (group B, n=20). Pertinent clinical and surgical data were collected. Hematological parameters (leukocyte and neutrophil counts) and biochemical parameters (C-reactive protein, cytokine tests) were determined pre-, on and post-CPB. There were an increase in leukocyte and neutrophil counts and a decline in hematocrit in both groups. In both groups, there was a raise after CPB, in C-reactive protein, IL-6, TNF-alpha, neutrophil elastase, and IL-10. However, the raises of elastase and TNF-alpha were significantly lower after the weaning of miniaturized CPB (116+/-46 ng/ml and 10+/-4 pg/ml, respectively) compared to standard CPB (265+/-120 ng/ml, P=0.01 and 18+/-7 pg/ml, P=0.03). The raise of IL-10 is also lower with miniaturized circuit (15+/-6 pg/ml) compared to standard circuit (51+/-26, P=0.004). This study demonstrates in aortic surgery, the lesser inflammatory response of a miniaturized CPB compared to a standard CPB. However, there is always some inflammation after CPB and a small bio-reactive free perfusion circuit is still to be found in open heart surgery.

  20. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis.

    PubMed

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

    2016-11-15

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Particulate oil shale inhalation and pulmonary inflammatory response in rats

    SciTech Connect

    Wilson, J.S.; Holland, L.M.; Halleck, M.S.; Martinez, E.; Saunders, G.

    1983-01-01

    This experiment detrimetal that long-term inhalation of shale dusts by rats elicits a limited inflammatory response in the lung less profound than that observed in animals exposed to equivalent levels of quartz alone. This observation suggests that organic and inorganic constituents of shale may provide a protective effect. The implications for fibrogenic disease are two-fold: (1) inhalation of oil shale dusts appeared to be less detriemtal than the inhalation of quartz along, and (2) there was no apparent synergistic action of quartz and the complex of organic materials present in shale. Animals exposed to shale dusts failed to develop any significant lung lesions, while all of the animals exposed to quartz developed granulomas and some frank fibrosis.

  2. Inflammatory response in the pig uterus induced by seminal plasma.

    PubMed

    Bischof, R J; Lee, C S; Brandon, M R; Meeusen, E

    1994-03-01

    The immunological and physiological influence of seminal plasma on the local uterine environment was investigated by immunohistochemical and flow cytometrical studies on uterine tissues and lymph nodes taken from gilts after mating with a vasectomised boar and from control, unmated gilts. These studies revealed that mating with a vasectomised boar induces an acute transient inflammatory response in the endometrium resulting in marked changes in the presence and distribution of leukocytes and extensive proliferation of the endometrial glands. At the same time there was an increase in CD8L and sIg+ cells and an up-regulation of MHC class II and IL-2 receptor expression in the uterine lymph nodes of mated pigs. This would suggest that seminal plasma deposited in the uterus can activate cells in the local draining lymph nodes. Together, these results demonstrate in utero that pronounced immunological and physiological changes are induced in vivo by seminal plasma.

  3. Inflammatory Response to Burn Trauma: Nicotine Attenuates Proinflammatory Cytokine Levels

    PubMed Central

    Papst, S.; Reimers, K.; Stukenborg-Colsman, C.; Steinstraesser, L.; Vogt, P. M.; Kraft, T.; Niederbichler, A. D.

    2014-01-01

    Objective: The immune response to an inflammatory stimulus is balanced and orchestrated by stimulatory and inhibitory factors. After a thermal trauma, this balance is disturbed and an excessive immune reaction with increased production and release of proinflammatory cytokines results. The nicotine-stimulated anti-inflammatory reflex offsets this. The goal of this study was to verify that transdermal administration of nicotine downregulates proinflammatory cytokine release after burn trauma. Methods: A 30% total body surface area full-thickness rat burn model was used in Sprague Dawley rats (n = 35, male). The experimental animals were divided into a control group, a burn trauma group, a burn trauma group with additional nicotine treatment, and a sham + nicotine group with 5 experimental animals per group. The last 2 groups received a transdermal nicotine administration of 1.75 mg. The concentrations of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 were determined in homogenates of hearts, livers, and spleens 12 or 24 hours after burn trauma. Results: Experimental burn trauma resulted in a significant increase in cytokine levels in hearts, livers, and spleens. Nicotine treatment led to a decrease of the effect of the burn trauma with significantly lower concentrations of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 compared to the trauma group. Conclusions: This study confirms in a standardized burn model that stimulation of the nicotinic acetylcholine receptor is involved in the regulation of effectory molecules of the immune response. Looking at the results of our study, further experiments designed to explore and evaluate the potency and mechanisms of the immunomodulating effects of this receptor system are warranted. PMID:25671045

  4. Coronavirus Infection in Ferrets: Antigen Distribution and Inflammatory Response.

    PubMed

    Doria-Torra, G; Vidaña, B; Ramis, A; Amarilla, S P; Martínez, J

    2016-11-01

    Multisystemic granulomatous lesions are the most common finding in ferrets infected by ferret systemic coronavirus (FRSCV). To characterize the inflammatory response developed against this virus, lesions from 4 naturally infected ferrets were examined. Lesions were classified into the 4 known types of granulomas (granulomas without necrosis [G], granulomas with necrosis [G-N], granulomas with neutrophils [G-NL], and diffuse granulomatous inflammation [DG]). The cellular composition of the lesions was characterized on the basis of cellular morphology and immunohistochemistry using markers for T and B-lymphocytes, plasma cells, macrophages, and neutrophils. The extent and distribution of viral antigen expression was also assessed. In G lesions, macrophages were mainly located in the center of the granuloma, with a moderate number of T-lymphocytes scattered among the macrophages, plasma cells, and B-lymphocytes. G-N lesions exhibited a necrotic center surrounded by abundant macrophages, some T-lymphocytes, plasma cells, and a few B-lymphocytes. In G-NL lesions, there was a central area dominated by neutrophils with low numbers of macrophages, plasma cells, and lymphocytes. DG presented similar cell proportions, but distributed evenly throughout the lesions. FRSCV was expressed in G, G-NL, G-N, and DG, with decreasing numbers of immunoreactive cells. This study reveals the important role of macrophages in the inflammatory response of ferrets against the virus and the variable proportions of leukocytes among different types of lesions, indicating their variable age. The results also confirm the similarities of the disease in ferrets to feline infectious peritonitis.

  5. Characterization of the inflammatory response during Ehrlich ascitic tumor development.

    PubMed

    Fernandes, Patrícia Dias; Guerra, Fabiana S; Sales, Natália M; Sardella, Thais B; Jancar, Sonia; Neves, Josiane S

    2015-01-01

    Ehrlich tumor is a mammary adenocarcinoma with aggressive behavior. Inoculated in mice peritoneal cavity, the Ehrlich tumor grows in ascitic form (EAT). Since inflammation modulates tumor progression we further investigated the inflammatory response during EAT growth. Balb/C mice were intraperitoneal inoculated with 5×10(5) Ehrlich cells and after every 2days, blood samples were collected for hemoglobin, hematocrit, platelets and leukocytes counts. The ascitic fluid was collected for protein concentration and cell count. Phenotype analysis of the peritoneal cells was made by FACS, prostaglandin E2 (PGE2) and cytokines by ELISA, nitric oxide (NO) by nitrate conversion protocol, and cyclooxygenase-1 (COX1), COX2 and inducible nitric oxide synthase (iNOS) by immunoblotting. Following EAT inoculation into the peritoneal cavity there was a rapid increase in ascitis volume and protein concentration. The cell number in ascitis remained stable until day 8 (lag phase) followed by a sharp increase. As tumor progressed, blood leukocytes increased and erythrocyte decreased. Phenotypic analysis showed that during the lag phase the percentage of F4/80(+) cells remained similar to control levels and around 7% of this population was also positive for the GR1 marker. These double-positive cells (probably inflammatory monocytes) markedly increased at day 6. The percentage of F4/80-GR1(+)cells (probably neutrophils) was low and did not significantly vary during tumor progression. CD4(+) and CD8(+) cells were not detected in the time points analyzed. iNOS and COX1 expression increased after day 2 reaching peak levels on day 10. COX2 enzyme expression did not change significantly over time. Sustained increase in PGE2 and NO levels was observed. IL-10 and MCP-1 peaked at day 14 and IL-1β increased progressively till day 10. IFN-γ levels were low till day 10, increasing progressively after that. These data extended the characterization of the inflammatory response during Ehrlich

  6. Sleep Disturbance and Older Adults' Inflammatory Responses to Acute Stress

    PubMed Central

    Heffner, Kathi L.; Ng, H. Mei; Suhr, Julie A.; France, Christopher R.; Marshall, Gailen D.; Pigeon, Wilfred R.; Moynihan, Jan A.

    2013-01-01

    Objectives Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Design Observational study of community-dwelling, healthy older adults. Setting Participants completed the study in a clinical research laboratory of a mid-sized university. Participants Generally healthy, community-dwelling men and women 50 years of age and older. Measurements IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Results Participants categorized as poor sleepers based on Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors compared to good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Conclusions Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation. PMID:22327621

  7. Sleep disturbance and older adults' inflammatory responses to acute stress.

    PubMed

    Heffner, Kathi L; Ng, H Mei; Suhr, Julie A; France, Christopher R; Marshall, Gailen D; Pigeon, Wilfred R; Moynihan, Jan A

    2012-09-01

    Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Observational study of community-dwelling, healthy older adults. Participants completed the study in a clinical research laboratory of a mid-sized university. Generally healthy, community-dwelling men and women age 50 and older. IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Participants categorized as poor sleepers on the basis of Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors than good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation.

  8. Human adjuvant-related syndrome or autoimmune/inflammatory syndrome induced by adjuvants. Where have we come from? Where are we going? A proposal for new diagnostic criteria.

    PubMed

    Alijotas-Reig, J

    2015-09-01

    In 1964, Miyoshi reported a series of patients with diverse symptoms after receiving treatment with silicone or paraffin fillers. Miyoshi named this condition 'human adjuvant disease'. Since then, the literature has been flooded with case reports and case series of granulomatous and systemic autoimmune disorders related to vaccines, infection or other adjuvants such as silicone and other biomaterials. A new term -autoimmune/inflammatory syndrome induced by adjuvants--has recently been coined for a process that includes several clinical features previously described by Miyoshi plus other clinical and laboratory parameters related to exposure to diverse external stimuli. Disorders such as siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, sick building syndrome and post-vaccination syndrome have been included in autoimmune/inflammatory syndrome induced by adjuvants. Disorders such as Spanish toxic oil syndrome and Ardystil syndrome could also be included. Furthermore, biomaterials other than silicone should also be considered as triggering factors for these adjuvant-related syndromes. New diagnostic criteria in this field have been proposed. Nevertheless, many of these criteria are too subjective, leading to some patients being diagnosed with chronic fatigue syndrome or other 'central sensitization syndromes'. Diagnostic criteria based only on objective clinical and laboratory data to be further discussed and validated are proposed herein.

  9. Criminal Responsibility of the Frontal Lobe Syndrome.

    PubMed

    Sener, Mustafa Talip; Ozcan, Halil; Sahingoz, Sadik; Ogul, Hayri

    2015-10-01

    Neurological and/or psychiatric symptoms might be detected due to damage of frontal lobes as detected in damages of many brain regions. Frontal lobe syndrome (FLS) occurs as a result of damage in prefrontal region due to various causes. Symptoms due to prefrontal region damage, varies according to the size and location of the lesion. In most of the cases; executive dysfunctions, attention deficits, inconsistencies in social life, impulse control problems, obsessive behaviors and violence behaviors are common clinical signs. Behavioral symptoms seen in FLS can be confused with personality disorders and negative symptoms of schizophrenia. FLS is a neuropsychiatric disorder rarely assessed in forensic psychiatry and in terms of detection of criminal responsibility. In this case report, criminal responsibility in FLS was assessed through a FLS case in which an offense of "threat" was committed and investigated in terms of criminal responsibility.

  10. Cytotoxic mediators in paradoxical HIV-tuberculosis immune reconstitution inflammatory syndrome.

    PubMed

    Wilkinson, Katalin A; Walker, Naomi F; Meintjes, Graeme; Deffur, Armin; Nicol, Mark P; Skolimowska, Keira H; Matthews, Kerryn; Tadokera, Rebecca; Seldon, Ronnett; Maartens, Gary; Rangaka, Molebogeng X; Besra, Gurdyal S; Wilkinson, Robert J

    2015-02-15

    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates combined antiretroviral therapy and antituberculosis therapy in HIV-1-coinfected tuberculosis patients. The immunopathological mechanisms underlying TB-IRIS are incompletely defined, and improved understanding is required to derive new treatments and to reduce associated morbidity and mortality. We performed longitudinal and cross-sectional analyses of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB-coinfected patients commencing antiretroviral therapy who did not develop TB-IRIS). Freshly isolated PBMC stimulated with heat-killed Mycobacterium tuberculosis H37Rv (hkH37Rv) were used for IFN-γ ELISPOT and RNA extraction. Stored RNA was used for microarray and RT-PCR, whereas corresponding stored culture supernatants were used for ELISA. Stored PBMC were used for perforin and granzyme B ELISPOT and flow cytometry. There were significantly increased IFN-γ responses to hkH37Rv in TB-IRIS, compared with non-IRIS PBMC (p = 0.035). Microarray analysis of hkH37Rv-stimulated PBMC indicated that perforin 1 was the most significantly upregulated gene, with granzyme B among the top five (log2 fold difference 3.587 and 2.828, respectively), in TB-IRIS. Downstream experiments using RT-PCR, ELISA, and ELISPOT confirmed the increased expression and secretion of perforin and granzyme B. Moreover, granzyme B secretion reduced in PBMC from TB-IRIS patients during corticosteroid treatment. Invariant NKT cell (CD3(+)Vα24(+)) proportions were higher in TB-IRIS patients (p = 0.004) and were a source of perforin. Our data implicate the granule exocytosis pathway in TB-IRIS pathophysiology. Further understanding of the immunopathogenesis of this condition will facilitate development of specific diagnostic and improved therapeutic options.

  11. Incidence of Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome and Impact on Patient Outcome

    PubMed Central

    Bonnet, Maryline; Baudin, Elisabeth; Jani, Ilesh V.; Nunes, Elizabete; Verhoustraten, François; Calmy, Alexandra; Bastos, Rui; Bhatt, Nilesh B.; Michon, Christophe

    2013-01-01

    Objectives and Design We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) occurring within 12 weeks of starting antiretroviral therapy, and to evaluate its association with patient outcome at 48 weeks. Methods HIV-tuberculosis co-infected and antiretroviral therapy-naïve adults with less than 250 CD4/mm3 were randomized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment, and were then followed for 48 weeks. Tuberculosis cases were diagnosed using WHO guidelines, and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS. Results The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm3 and HIV-1 RNA of 5.6 log10 copies/mL. Mortality at week 48 was 6.1% (35/573). Fifty-three (9.2%) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy. Being female and having a low CD4 count, high HIV-1 RNA load, low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS. After adjustment for baseline body mass index, CD4 count and hemoglobin, occurrence of tuberculosis-IRIS was independently associated with 48-week mortality (aOR 2.72 95%CI 1.14-6.54). Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS. Conclusion In this large prospective cohort, tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation. PMID:24367678

  12. Systemic inflammatory response due to chloroform intoxication--an uncommon complication.

    PubMed

    Dettling, A; Stadler, K; Eisenbach, C; Skopp, G; Haffner, H T

    2016-03-01

    Well-known adverse effects of chloroform are drowsiness, nausea, and liver damage. Two cases with an uncommon complication due to chloroform intoxication are presented. In the first case, a general physician, because of nausea and dyspnea, admitted a 34-year-old woman to hospital. She developed a toxic pulmonary edema requiring mechanical ventilation for a few days, and a systemic inflammatory response syndrome (SIRS) with elevated white blood cell counts, a moderate increase of C-reactive protein, and slightly elevated procalcitonin levels. There were inflammatory altered skin areas progressing to necrosis later on. However, bacteria could be detected neither in blood culture nor in urine. Traces of chloroform were determined from a blood sample, which was taken 8 h after admission. Later, the husband confessed to the police having injected her chloroform and put a kerchief soaked with chloroform over her nose and mouth. In the second case, a 50-year-old man ingested chloroform in a suicidal attempt. He was found unconscious in his house and referred to a hospital. In the following days, he developed SIRS without growth of bacteria in multiple blood cultures. He died several days after admission due to multi-organ failure. SIRS in response to chloroform is a rare but severe complication clinically mimicking bacterial-induced sepsis. The mechanisms leading to systemic inflammation after chloroform intoxication are currently unclear. Possibly, chloroform and/or its derivates may interact with pattern recognition receptors and activate the same pro-inflammatory mediators (cytokines, interleukins, prostaglandins, leukotrienes) that cause SIRS in bacterial sepsis.

  13. Thiamine-responsive megaloblastic anemia syndrome.

    PubMed

    Bay, Ali; Keskin, Mehmet; Hizli, Samil; Uygun, Hatice; Dai, Alper; Gumruk, Fatma

    2010-10-01

    Thiamine-responsive megaloblastic anemia (TRMA) syndrome usually associated with diabetes mellitus, anemia and deafness, due to mutations in SLC19A2, encoding a thiamine transporter protein. The onset of disease is usually seen during infancy or at early childhood and most of the TRMA patients are originated from consanguineous families. In this case, we report a 5-month-old boy who had diagnosis of TRMA during evaluations for his anemia and thrombocytopenia. The diagnosis of TRMA should be kept in mind in differential diagnosis of megaloblastic anemia especially in the populations where the consanguinity is frequent.

  14. Focal, steroid responsive myositis causing dropped head syndrome.

    PubMed

    Biran, I; Cohen, O; Diment, J; Peyser, A; Bahnof, R; Steiner, I

    1999-06-01

    The dropped head syndrome, which occurs in a variety of neuromuscular disorders, is usually not due to an inflammatory process and generally either self-limited or nonresponsive to therapy. We present an 80-year-old woman who developed progressive neck weakness over a few months due to a focal and restricted inflammatory process involving the neck extensor muscles. She responded dramatically to treatment with immunosuppressive therapy.

  15. Randomized study comparing inflammatory response after tonsillectomy versus tonsillotomy.

    PubMed

    Kordeluk, Sofia; Goldbart, Aviv; Novack, Lena; Kaplan, Daniel Michael; El-Saied, Sabri; Alwalidi, Musa; Shapira-Parra, Angelica; Segal, Nili; Slovik, Yuval; Max, Puterman; Joshua, Ben-Zion

    2016-11-01

    To determine if there was a difference in the inflammatory reaction after tonsil surgery with "traditional" techniques (tonsillectomy and adenoidectomy or TA) compared to partial intracapsular tonsillectomy and adenoidectomy (PITA). Randomized, double-blind study. tertiary care academic hospital. Children under the age of 16 years with a diagnosis of obstructive sleep disordered breathing were randomly allocated into three study groups: TA with electrocautery (n = 34), PITA with CO2 laser (n = 30) and PITA with debrider (n = 28). All of the children underwent adenoidectomy with a current at the same surgical procedure. c-reactive protein level (CRP) was the primary endpoint. In addition, the following were assessed: white blood cells (WBC), neutrophils (NEU), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Pre- and post-procedure measurements were compared between the groups. Parents filled out a questionnaire daily during the first postoperative week assessing pain, swallowing and snoring. CRP levels ascended higher in the PITA groups after surgery (p = 0.023), WBC and NEU showed the same pattern, IL-6 levels were higher in PITA group and there was no difference in TNF-alpha levels between the two types of procedures. Postoperative pain and postoperative hemorrhage were significantly lower in the PITA groups as compared to the TA group (p = 0.01 and 0.048). PITA in comparison to TA is associated with lower morbidity; however, the inflammatory response does not differ significantly in the first 24 h after surgery. Additional long-term studies assessing efficacy of PITA are warranted. Level 1, prospective randomized controlled trial.

  16. Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

    PubMed Central

    Zhao, Jing; Ha, Yonju; Liou, Gregory I.; Gonsalvez, Graydon B.; Smith, Sylvia B.; Bollinger, Kathryn E.

    2014-01-01

    Purpose. To evaluate the effects of the σ 1 receptor (σR1) agonist, (+)-pentazocine, on lipopolysaccharide (LPS)–induced inflammatory changes in retinal microglia cells. Methods. Retinal microglia cells were isolated from Sprague-Dawley rat pups. Cells were treated with LPS with or without (+)-pentazocine and with or without the σR1 antagonist BD1063. Morphologic changes were assayed. Cell viability was assessed by using MTT assay. Supernatant levels of tumor necrosis factor α (TNF-α), interleukin 10, (IL-10), monocyte chemoattractant protein-1 (MCP-1), and nitric oxide (NO) were determined. Reactive oxygen species (ROS) formation was assayed, and levels of mitogen-activated protein kinases (MAPKs) were analyzed by using Western blot. Results. The σR1 protein was expressed in retinal microglia. Incubation with LPS and/or (+)-pentazocine did not alter cell viability or σR1 protein levels. Incubation with LPS for 24 hours induced a marked change in microglial morphology and a significant increase in secreted levels of TNF-α, IL-10, MCP-1, and NO. Pretreatment with (+)-pentazocine inhibited the LPS-induced morphologic changes. Release of TNF-α, IL-10, MCP-1, and NO was reduced with (+)-pentazocine. Intracellular ROS formation was suppressed with (+)-pentazocine. Phosphorylation of extracellular signal–regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was reduced in the presence of (+)-pentazocine. The σR1 antagonist BD1063 blocked the (+)-pentazocine–mediated inhibition of LPS-induced morphologic changes. In addition, BD1063 treatment blocked (+)-pentazocine–mediated suppression of LPS-induced TNF-α, IL-10, MCP-1, NO, and intracellular ROS release. Conclusions. Treatment with (+)-pentazocine suppressed inflammatory responses of retinal microglia and inhibited LPS-induced activation of ERK/JNK MAPK. In neurodegenerative disease, (+)-pentazocine may exert neuroprotective effects through manipulation of microglia. PMID:24812552

  17. Early inflammatory response in polytraumatized patients: Cytokines and heat shock proteins. A pilot study.

    PubMed

    Guisasola, M C; Ortiz, A; Chana, F; Alonso, B; Vaquero, J

    2015-09-01

    In the initial phases after polytrauma there is an hyperinflammatory state that sometimes leads to multiple organ dysfunction syndrome (MODS) and death, and that appears to be responsible for posttraumatic immunosuppression; among the trigger endogenous stimuli, heat shock proteins (HSPs) have been proposed. The objectives of this study were to analyze if some inflammatory mediators can be considered prognostic biomarkers of outcome, and the possible role of HSPA1A in posttraumatic immunosuppression. Cytokines and HSPs could be early prognostic biomarkers of inflammatory and immune response in polytrauma patients. A prospective observational descriptive pilot study was carried out, evaluating the early inflammatory and stress response of 18 polytraumatized patients (ISS>16) on hospital admission, at 12hours, 24hours, and 48hours posttrauma. Variable means were compared using non-parametric tests; qualitative and quantitative variables were analyzed using a Spearman's correlation test. Seven patients met criteria for MODS. Statistically significant changes were recorded in leukocyte count, C-reactive-protein (CRP), IL-6, TNF-α, and IL-1ß concentrations. HSPA1A levels were significantly higher immediately after the accident followed by gradual lowering. Anti-Hsp70 antibodies showed a significant reduction in all the studied time-points. MODS did not influence either plasma levels of leukocytes, fibrinogen, RCP or anti-Hsp70, but patients with MODS had higher plasma levels of IL-6 and TNF-α and a slower decrease of HSPA1A concentrations. The higher serum concentrations of TNF-α and IL-6 found in patients with MODS, suggests a possible role as potential early predictive markers for systemic inflammatory response and clinical complications. The higher levels of HSPA1A in patients with MODS, allows proposing HSPA1A as a useful prognostic trauma biomarker early after severe injury and to consider a "damage control surgery". The significant reduction in the levels of

  18. Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

    PubMed

    Hodkinson, Duncan J; Khawaja, Nadine; OʼDaly, Owen; Thacker, Michael A; Zelaya, Fernando O; Wooldridge, Caroline L; Renton, Tara F; Williams, Steven C R; Howard, Matthew A

    2015-07-01

    Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction, and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow under pain-free conditions (presurgery). However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.

  19. IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines

    PubMed Central

    Li, Xinyuan; Mai, Jietang; Virtue, Anthony; Yin, Ying; Gong, Ren; Sha, Xiaojin; Gutchigian, Stefanie; Frisch, Andrew; Hodge, Imani; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies. PMID:22438968

  20. Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

    PubMed Central

    Park, Na-Young; Valacchi, Giuseppe; Lim, Yunsook

    2010-01-01

    Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA), a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage). We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses. PMID:20871865

  1. Impairment measures versus inflammatory RODS in GBS and CIDP: a responsiveness comparison.

    PubMed

    Vanhoutte, Els K; Draak, Thomas H P; Gorson, Kenneth C; van Nes, Sonja I; Hoeijmakers, Janneke G J; Van der Pol, W-Ludo; Notermans, Nicolette C; Lewis, Richard A; Nobile-Orazio, Eduardo; Léger, Jean-Marc; Van den Bergh, Peter Y K; Lauria, Giuseppe; Bril, Vera; Katzberg, Hans; Lunn, Michael P T; Pouget, Jean; van der Kooi, Anneke J; Hahn, Angelika F; van Doorn, Pieter A; Cornblath, David R; van den Berg, Leonard H; Faber, Catharina G; Merkies, Ingemar S J

    2015-09-01

    This study aimed to 'define responder' through the concept of minimum clinically important differences using the individually obtained standard errors (MCID-SE) and a heuristic 'external criterion' responsiveness method in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One hundred and fourteen newly diagnosed or relapsing patients (GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I-RODS), Rasch-transformed MRC sum score (RT-MRC), and Rasch-transformed modified-INCAT-sensory scale (RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off ≥1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status 'thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic 'U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I-RODS > RT-MRC > RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of 'being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I-RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP. © 2015 Peripheral Nerve Society.

  2. Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS

    PubMed Central

    Wolfson, Marla R.; Wu, Jichuan; Hubert, Terrence L.; Gregory, Timothy J.; Mazela, Jan; Shaffer, Thomas H.

    2013-01-01

    Background Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants. Methods Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination. Results SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant. Conclusion These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant. PMID:22821059

  3. Mitochondrial DNA-Induced Inflammatory Responses and Lung Injury in Thermal Injury Rat Model: Protective Effect of Epigallocatechin Gallate.

    PubMed

    Liu, Ruiqi; Xu, Fei; Si, Si; Zhao, Xueshan; Bi, Siwei; Cen, Ying

    Lungs are easily damaged by the inflammatory responses induced after extensive burns. The aim here was to investigate the protective role of epigallocatechin gallate (EGCG) in mitochondrial DNA (mtDNA)-mediated inflammatory responses and acute respiratory distress syndrome (ARDS) in a rat model of thermal injury. Male Sprague-Dawley rats were randomly assigned to five groups. In the first experiment, a full-thickness thermal injury or control procedure, covering 30% of the TBSA, was inflicted on three groups designated as the thermal injury, EGCG, and sham control groups. In the second experiment, another two groups were established by transfusion with either mtDNA (mtDNA group) or phosphate-buffered saline (phosphate-buffered saline group). Blood samples and lung tissue from all five groups were collected and the plasma concentrations of mtDNA and inflammatory mediators were measured. Bronchoalveolar lavage fluid was collected and histological analysis of the lung tissue was performed to evaluate the severity of ARDS. Significant increases in mtDNA and inflammatory mediator plasma concentrations were seen in the thermal injury and EGCG groups when compared with controls (P < .05). The plasma concentrations of mtDNA and inflammatory mediators were significantly decreased after the administration of EGCG (P < .05). EGCG also significantly reduced the severity of acute lung injury (P < .05). Intravenous administration of mtDNA significantly increased concentrations of inflammatory mediators and caused severe ARDS (P < .05). Our results suggest that mtDNA is important for thermal injury-induced inflammation and associated ARDS. EGCG possesses anti-inflammatory and lung-protective properties, and might act by limiting mtDNA release after thermal injury.

  4. Cryptococcal Immune Reconstitution Inflammatory Syndrome in HIV-1–infected individuals: Literature Review and Proposed Clinical Case Definitions

    PubMed Central

    Haddow, Lewis J; Colebunders, Robert; Meintjes, Graeme; Lawn, Stephen D; Elliott, Julian H; Manabe, Yukari C; Bohjanen, Paul R; Sungkanuparph, Somnuek; Easterbrook, Philippa J; French, Martyn A; Boulware, David R

    2011-01-01

    Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) may present as a clinical deterioration or new presentation of cryptococcal disease following initiation of antiretroviral therapy (ART) and is believed to be caused by recovery of cryptococcus-specific immune responses. We have reviewed the existing literature on C-IRIS to inform the development of a consensus case definition specific for paradoxical cryptococcal IRIS in patients with known cryptococcal disease prior to ART, and a second definition for incident cases of cryptococcosis developing during ART (here termed ART-associated cryptococcosis), a proportion of which are likely to be “unmasking” C-IRIS. These structured case definitions are intended for use in future clinical, epidemiologic and immunopathologic studies of C-IRIS, harmonizing diagnostic criteria, and facilitating comparisons between studies. As with tuberculosis-associated IRIS, these proposed definitions should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement. PMID:21029993

  5. Effects of azithromycin on shiga toxin production by Escherichia coli and subsequent host inflammatory response.

    PubMed

    Ohara, Tatsuki; Kojio, Seiichi; Taneike, Ikue; Nakagawa, Saori; Gondaira, Fumio; Tamura, Yukiko; Gejyo, Fumitake; Zhang, Hui-Min; Yamamoto, Tatsuo

    2002-11-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the human intestinal mucosa, produces Stx from phage, and causes the development of hemolytic-uremic syndrome via Stx-induced inflammatory cytokine production. Azithromycin exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin. Azithromycin decreased the tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin significantly suppressed Stx-induced TNF-alpha, IL-1beta, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immature-mouse model), all mice died within 7 days postinfection. Azithromycin administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice. Azithromycin may have a beneficial effect on STEC-associated disease.

  6. Radiation Promotes Colorectal Cancer Initiation and Progression by Inducing Senescence-Associated Inflammatory Responses

    PubMed Central

    Kim, Sang Bum; Bozeman, Ronald; Kaisani, Aadil; Kim, Wanil; Zhang, Lu; Richardson, James A.; Wright, Woodring E.; Shay, Jerry W.

    2015-01-01

    Proton radiotherapy is becoming more common since protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared to conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIR) which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence associated gene (P19Arf) are markedly increased. Following these changes loss of Casein kinase Iα (CKIα) and induction of chronic DNA damage and TP53 mutations are increased compared to x-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, CDDO-EA, reduces proton irradiation associated SIR and tumorigenesis. Thus, exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA. PMID:26477319

  7. Successful Treatment of immune Reconstitution Inflammatory syndrome-related Hemophagocytic Syndrome in an HIV Patient with Primary Effusion Lymphoma

    PubMed Central

    Zorzou, Markela-P.; Chini, Maria; Lioni, Athina; Tsekes, Georgios; Nitsotolis, Thomas; Tierris, Ioannis; Panagiotou, Nicolaos; Rontogianni, Dimitra; Harhalakis, Nicolaos; Lazanas, Marios

    2016-01-01

    Although the connection of [secondary hemophagocytic syndrome (sHS)] with HIV has been well documented, optimal treatment regimen is not well established. This is due not only to the rarity of the syndrome, but also to the heterogeneity of the involved population. Most cases are related to opportunistic infections or malignancies in advanced stage, but many cases are also related to seroconversion, in the primary infection setting. Moreover, in the [antiretroviral treatment (ART)] era, rare cases of ART-related sHS have been reported. In these, often fatal cases, an [immune reconstitution inflammatory syndrome (IRIS)] process is involved, posing a serious challenge to the treating physician. We hereby report a case of successful treatment of an HIV patient with primary effusion lymphoma who experienced sHS shortly after ART onset. Our patient, treated with high dose dexamethasone and gamma globulin, achieved complete remission. This case might hint possible therapeutic insights in the treatment of IRIS-related sHS. PMID:28090281

  8. The human intestinal microbiota of constipated-predominant irritable bowel syndrome patients exhibits anti-inflammatory properties

    PubMed Central

    Gobert, Alain P.; Sagrestani, Giulia; Delmas, Eve; Wilson, Keith T.; Verriere, Thomas G.; Dapoigny, Michel; Del’homme, Christophe; Bernalier-Donadille, Annick

    2016-01-01

    The intestinal microbiota of patients with constipated-predominant irritable bowel syndrome (C-IBS) displays chronic dysbiosis. Our aim was to determine whether this microbial imbalance instigates perturbation of the host intestinal mucosal immune response, using a model of human microbiota-associated rats (HMAR) and dextran sulfate sodium (DSS)-induced experimental colitis. The analysis of the microbiota composition revealed a decrease of the relative abundance of Bacteroides, Roseburia-Eubacterium rectale and Bifidobacterium and an increase of Enterobacteriaceae, Desulfovibrio sp., and mainly Akkermansia muciniphila in C-IBS patients compared to healthy individuals. The bacterial diversity of the gut microbiota of healthy individuals or C-IBS patients was maintained in corresponding HMAR. Animals harboring a C-IBS microbiota had reduced DSS colitis with a decreased expression of pro-inflammatory cytokines from innate, Th1, and Th17 responses. The pre-treatment of conventional C57BL/6 mice or HMAR with A. muciniphila, but not with Escherichia coli, prior exposure to DSS also resulted in a reduction of colitis severity, highlighting that the anti-inflammatory effect of the gut microbiota of C-IBS patients is mediated, in part, by A. muciniphila. This work highlights a novel aspect of the crosstalk between the gut microbiota of C-IBS patients and host intestinal homeostasis. PMID:27982124

  9. DISREGULATION OF INFLAMMATORY RESPONSES BY CHRONIC CIRCADIAN DISRUPTION

    PubMed Central

    Castanon-Cervantes, Oscar; Wu, Mingwei; Ehlen, J. Christopher; Paul, Ketema; Gamble, Karen L.; Johnson, Russell L.; Besing, Rachel C.; Menaker, Michael; Gewirtz, Andrew T.; Davidson, Alec J.

    2010-01-01

    Circadian rhythms modulate nearly every mammalian physiological process. Chronic disruption of circadian timing in shift work or during chronic jet lag in animal models leads to a higher risk of several pathologies. Many of these conditions in both shift workers and experimental models share the common risk factor of inflammation. Here we show that experimentally-induced circadian disruption altered innate immune responses. Endotoxemic shock induced by LPS was magnified leading to hypothermia and death after 4 consecutive weekly 6h phase-advances of the light-dark schedule, with 89% mortality compared with 21% in unshifted control mice. This may be due to a heightened release of pro-inflammatory cytokines in response to LPS treatment in shifted animals. Isolated peritoneal macrophages harvested from shifted mice exhibited a similarly heightened response to LPS in vitro, indicating that these cells are a target for jet lag. Sleep deprivation and stress are known to alter immune function and are potential mediators of the effects we describe. However polysomnographic recording in mice exposed to the shifting schedule revealed no sleep loss, and stress measures were not altered in shifted mice. In contrast, we observed altered or abolished rhythms in the expression of clock genes in the central clock, liver, thymus and peritoneal macrophages in mice after chronic jet lag. We conclude that circadian disruption, but not sleep loss or stress, are associated with jet lag-related disregulation of the innate immune system. Such immune changes might be a common mechanism for the myriad negative health effects of shift work. PMID:20944004

  10. Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder.

    PubMed

    Martinac, Marko; Pehar, Davor; Karlović, Dalibor; Babić, Dragan; Marcinko, Darko; Jakovljević, Miro

    2014-03-01

    Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but

  11. Early growth response 1 mediates the systemic and hepatic inflammatory response initiated by hemorrhagic shock.

    PubMed

    Prince, Jose M; Ming, Mei Jian; Levy, Ryan M; Liu, Shubing; Pinsky, David J; Vodovotz, Yoram; Billiar, Timothy R

    2007-02-01

    Hemorrhagic shock (HS) is a major cause of morbidity and mortality in trauma patients. The early growth response 1 (Egr-1) transcription factor is induced by a variety of cellular stresses, including hypoxia, and may function as a master switch to trigger the expression of numerous key inflammatory mediators. We hypothesized that HS would induce hepatic expression of Egr-1 and that Egr-1 upregulates the inflammatory response after HS. The Egr-1 mice and wild-type (WT) controls (n>or=5 for all groups) were subjected to HS alone or HS followed by resuscitation (HS/R). Other mice were subjected to a sham procedure which included general anesthesia and vessel cannulation but no shock (sham). After the HS, HS/R, or sham procedures, mice were euthanized for determination of serum concentrations of interleukin (IL) 6, IL-10, and alanine aminotransferase. Northern blot analysis was performed to evaluate Egr-1 messenger RNA (mRNA) expression. Liver whole cell lysates were evaluated for Egr-1 protein expression by Western blot analysis. Hepatic expression of IL-6, granulocyte colony-stimulating factor, and intracellular adhesion molecule 1 mRNA was determined by semiquantitative reverse transcriptase-polymerase chain reaction. The Egr-1 DNA binding was assessed using the electrophoretic mobility shift assay. Hemorrhagic shock results in a rapid and transient hepatic expression of Egr-1 mRNA in WT mice by 1 h, whereas protein and DNA binding activity was evident by 2.5 h. The Egr-1 mRNA expression diminished after 4 h of resuscitation, whereas Egr-1 protein expression and DNA binding activity persisted through resuscitation. The Egr-1 mice exhibited decreased levels of hepatic inflammatory mediators compared with WT controls with a decrease in hepatic mRNA levels of IL-6 by 42%, granulocyte colony-stimulating factor by 39%, and intracellular adhesion molecule 1 by 43%. Similarly, Egr-1 mice demonstrated a decreased systemic inflammatory response and hepatic injury after HS

  12. Inflammatory cytokines in an experimental model for the multiple organ dysfunction syndrome.

    PubMed

    Jansen, M J; Hendriks, T; Vogels, M T; van der Meer, J W; Goris, R J

    1996-07-01

    To investigate the alterations in circulating pro-inflammatory cytokines and cytokine production by peritoneal macrophages during the development of multiple organ dysfunction syndrome. Prospective, controlled laboratory study on zymosan-induced generalized inflammation in mice. Single intraperitoneal administration of zymosan induces, over a 12-day period, a triphasic illness in mice; the third phase, from day 6 onward, resembles multiple organ dysfunction syndrome. Animal research laboratory. C57BL/6CRW mice received a single intraperitoneal dose of zymosan on day 0, and standard numbers of animals were killed at different time points up until day 12. Plasma concentrations of interleukin (IL)-1 alpha and IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured from 3 hrs to 12 days after administration of zymosan. At the same time points, both lipopolysaccharide-stimulated and unstimulated production of these cytokines by peritoneal macrophages were measured in vitro. Plasma TNF and IL-6 concentrations transiently increased during the first 24 hrs after administration of zymosan. After 8 days, a prominent peak of biologically inactive TNF was observed. Both unstimulated and lipopolysaccharide-stimulated cytokine production by peritoneal cells showed profound changes during the experimental period. These findings seem to confirm our hypothesis that the macrophages are in a continuously activated state and altered in their function, when the animals develop multiple organ dysfunction syndrome. Further studies are needed to elucidate what happens with these cytokines at the tissue level, to better understand the pathophysiology of multiple organ dysfunction syndrome.

  13. [Comparison of symptoms, laboratory parameters and illness perception in patients with irritable bowel syndrome and inflammatory bowel disease].

    PubMed

    Bor, Renáta; Balanyi, Zsolt; Farkas, Klaudia; Bálint, Anita; Rutka, Mariann; Szűcs, Mónika; Milassin, Ágnes; Szepes, Zoltán; Nagy, Ferenc; Molnár, Tamás

    2015-06-07

    Symptoms-based differential diagnosis of irritable bowel syndrome and inflammatory bowel disease is often difficult. To determine the differential diagnostic ability of clinical activity indexes and psychological questionnaires in these conditions, which have never been simultaneously analyzed. 37 irritable bowel syndrome, 54 Crohn's disease and 41 ulcerative colitis patients were enrolled in the study. The patients completed the Crohn's Disease Activity Index test, Illness Perception Questionnaire and Inflammatory Bowel Disease Questionnaire. Hematocrit and C-reactive protein level of patients were also analyzed. Patients with irritable bowel syndrome felt their abdominal pain more severe than the other two groups (p = 0.005), while the quality of life was the worst in Crohn's disease (p = 0.0000001). Significantly more patients with inflammatory bowel disease considered that their condition is lifelong (p = 0.000781). The knowledge about disease was more appropriate in patients with inflammatory bowel disease (p = 0.00629). No significant difference was found in hematocrit levels, but the C-reactive protein level was significantly lower in patients with irritable bowel syndrome (p = 0.001). Illness perception questionnaires and C-reactive protein can help in the differentiation of inflammatory bowel disease from irritable bowel syndrome.

  14. Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

    PubMed Central

    Lins, Nara; Mourão, Luiz; Trévia, Nonata; Passos, Aline; Farias, José Augusto; Assunção, Jarila; Bento-Torres, João; Consentino Kronka Sosthenes, Marcia; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa

    2016-01-01

    We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits. PMID:28003864

  15. Chitin and Its Effects on Inflammatory and Immune Responses.

    PubMed

    Elieh Ali Komi, Daniel; Sharma, Lokesh; Dela Cruz, Charles S

    2017-03-01

    Chitin, a potential allergy-promoting pathogen-associated molecular pattern (PAMP), is a linear polymer composed of N-acetylglucosamine residues which are linked by β-(1,4)-glycosidic bonds. Mammalians are potential hosts for chitin-containing protozoa, fungi, arthropods, and nematodes; however, mammalians themselves do not synthetize chitin and thus it is considered as a potential target for recognition by mammalian immune system. Chitin is sensed primarily in the lungs or gut where it activates a variety of innate (eosinophils, macrophages) and adaptive immune cells (IL-4/IL-13 expressing T helper type-2 lymphocytes). Chitin induces cytokine production, leukocyte recruitment, and alternative macrophage activation. Intranasal or intraperitoneal administration of chitin (varying in size, degree of acetylation and purity) to mice has been applied as a routine approach to investigate chitin's priming effects on innate and adaptive immunity. Structural chitin present in microorganisms is actively degraded by host true chitinases, including acidic mammalian chitinases and chitotriosidase into smaller fragments that can be sensed by mammalian receptors such as FIBCD1, NKR-P1, and RegIIIc. Immune recognition of chitin also involves pattern recognition receptors, mainly via TLR-2 and Dectin-1, to activate immune cells to induce cytokine production and creation of an immune network that results in inflammatory and allergic responses. In this review, we will focus on various immunological aspects of the interaction between chitin and host immune system such as sensing, interactions with immune cells, chitinases as chitin degrading enzymes, and immunologic applications of chitin.

  16. Effect of riboflavin or pyridoxine deficiency on inflammatory response.

    PubMed

    Lakshmi, R; Lakshmi, A V; Divan, P V; Bamji, M S

    1991-01-01

    Inflammatory response has been assessed in riboflavin or pyridoxine deficient rats. Edema was increased by 54% in pyridoxine deficiency as compared to weight-matched control rats. Food restriction per se reduced the volume of edema by 63%. In pyridoxine deficiency, concentrations of thiobarbituric acid reactive substances (which indicate the extent of lipid peroxidation) increase by 30 and 43% respectively in the edematous tissues of the paw as well as in the wounded skin. Both these parameters were not affected by riboflavin deficiency. Activities of NADPH oxidase and superoxide dismutase in elicited leukocytes from peritoneal cavity were reduced by 54 and 52%, respectively, in riboflavin deficiency but were unaltered in pyridoxine deficiency. Superoxide level and acid phosphatase activity were not influenced by either of the deficiencies, whereas hydrogen peroxide level was increased by 48% in riboflavin deficiency. Food restriction did not affect leukocyte enzymes or the levels of reduced oxygen species. The data suggest that inflammation is enhanced in pyridoxine deficiency but not in riboflavin deficiency.

  17. Candida albicans-induced inflammatory response in human keratinocytes.

    PubMed

    Wollina, U; Künkel, W; Bulling, L; Fünfstück, C; Knöll, B; Vennewald, I; Hipler, U-C

    2004-06-01

    Candida albicans strains 3153a, ATCC 48867, CBS 2730, DSM 70014, and Vir 13 were cultivated and sterile C. albicans filtrates were produced. The interaction of soluble Candida factors of these infiltrates with human HaCaT keratinocytes was assayed in vitro. The following parameters were analyzed: cell proliferation, protein synthesis, nuclear matrix protein (NMP) 41 release, cytokine release (IL-1beta, soluble IL-2 receptor, IL-6, and IL-8), and reactive oxygen species (ROS). Cell counts at 1, 12, and 24 h were significantly lower for C. albicans strains CBS 2730 and VIR 13 (P < 0.05). There was no significant change for the remaining strains. Neither the protein synthesis nor the NMP-41 release was significantly affected. IL-6 and IL-8 were stimulated by C. albicans filtrates to different amounts with higher levels in strains of low virulence. There was no effect on the other cytokines. The production of ROS by HaCaT keratinocytes was suppressed. The induction of an inflammatory keratinocyte response by soluble C. albicans factors may play a role among the host-yeast interactions.

  18. Role of Fiber Length on Phagocytosis & Inflammatory Response

    NASA Astrophysics Data System (ADS)

    Turkevich, Leonid; Stark, Carahline; Champion, Julie

    2014-03-01

    Asbestos fibers have long been associated with lung cancer death. The inability of immune cells (e.g. macrophages) to effectively remove asbestos leads to chronic inflammation and disease. This study examines the role of fiber length on toxicity at the cellular level using model glass fibers. A major challenge is obtaining single diameter fibers but differing in length. Samples of 1 micron diameter fibers with different length distributions were prepared: short fibers (less than 15 microns) by aggressive crushing, and long fibers (longer than 15 microns) by successive sedimentation. Time-lapse video microscopy monitored the interaction of MH-S murine alveolar macrophages with the fibers: short fibers were easily internalized by the macrophages, but long fibers resisted internalization over many hours. Production of TNF- α (tumor necrosis factor alpha), a general inflammatory secreted cytokine, and Cox-2 (cyclo-oxygenase-2), an enzyme that produces radicals, each exhibited a dose-dependence that was greater for long than for short fibers. These results corroborate the importance of fiber length in both physical and biochemical cell response and support epidemiological observations of higher toxicity for longer fibers.

  19. Experimental obstructive cholestasis: the wound-like inflammatory liver response

    PubMed Central

    Aller, María-Angeles; Arias, Jorge-Luis; García-Domínguez, Jose; Arias, Jose-Ignacio; Durán, Manuel; Arias, Jaime

    2008-01-01

    Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them. Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis. It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration. PMID:19014418

  20. Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β Inhibition

    PubMed Central

    Goldbach-Mansky, Raphaela; Dailey, Natalie J.; Canna, Scott W.; Gelabert, Ana; Jones, Janet; Rubin, Benjamin I.; Kim, H. Jeffrey; Brewer, Carmen; Zalewski, Christopher; Wiggs, Edythe; Hill, Suvimol; Turner, Maria L.; Karp, Barbara I.; Aksentijevich, Ivona; Pucino, Frank; Penzak, Scott R.; Haverkamp, Margje H.; Stein, Leonard; Adams, Barbara S.; Moore, Terry L.; Fuhlbrigge, Robert C.; Shaham, Bracha; Jarvis, James N.; O’Neil, Kathleen; Vehe, Richard K.; Beitz, Laurie O.; Gardner, Gregory; Hannan, William P.; Warren, Robert W.; Horn, William; Cole, Joe L.; Paul, Scott M.; Hawkins, Philip N.; Pham, Tuyet Hang; Snyder, Christopher; Wesley, Robert A.; Hoffmann, Steven C.; Holland, Steven M.; Butman, John A.; Kastner, Daniel L.

    2014-01-01

    BACKGROUND Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation. METHODS We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1–receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare. RESULTS All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events. CONCLUSIONS Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations. (ClinicalTrials.gov number, NCT00069329.) PMID:16899778

  1. Anti-inflammatory effect of Taraxacum officinale leaves on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells.

    PubMed

    Koh, Yoon-Jeoung; Cha, Dong-Soo; Ko, Je-Sang; Park, Hyun-Jin; Choi, Hee-Don

    2010-08-01

    To investigate the efficacy and the mechanism of the anti-inflammatory effect of Taraxacum officinale leaves (TOLs), the effect of a methanol extract and its fractions recovered from TOLs on lipopolysaccharide (LPS)-induced responses was studied in the mouse macrophage cell line, RAW 264.7. Cells were pretreated with various concentrations of the methanol extract and its fractions and subsequently incubated with LPS (1 microg/mL). The levels of nitric oxide (NO), prostaglandin (PG) E(2), and pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined using enzyme-linked immunosorbent assays. Expressions of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and activation of mitogen-activated protein (MAP) kinases were analyzed using western blotting. The methanol extract and its fractions inhibited LPS-induced production of NO, pro-inflammatory cytokines, and PGE(2) in a dose-dependent manner. The chloroform fraction significantly suppressed production of NO, PGE(2), and two pro-inflammatory cytokines (TNF-alpha and IL-1beta) in a dose-dependent manner with 50% inhibitory concentration values of 66.51, 90.96, 114.76, and 171.06 microg/mL, respectively. The ethyl acetate fraction also inhibited production of the inflammatory molecules. The chloroform and ethyl acetate fractions reduced LPS-induced expressions of iNOS and COX-2 and activation of MAP kinases in a dose-dependent manner. Among the fractions of the methanol extract, the chloroform and ethyl acetate fractions exhibited the most effective anti-inflammatory activities. These results show that the anti-inflammatory effects of TOLs are probably due to down-regulation of NO, PGE(2), and pro-inflammatory cytokines and reduced expressions of iNOS and COX-2 via inactivation of the MAP kinase signal pathway.

  2. IL-37 inhibits the production of pro-inflammatory cytokines in MSU crystal-induced inflammatory response.

    PubMed

    Zeng, Mei; Dang, Wantai; Chen, Baofeng; Qing, Yufeng; Xie, Wenguang; Zhao, Mingcai; Zhou, Jingguo

    2016-09-01

    Acute gouty arthritis (AGA) is an auto-inflammatory disease characterized by resolving spontaneously, which suggests that negative feedback loops control inflammatory and immunological responses to monosodium urate (MSU) crystals. By now, the molecular mechanism for spontaneous resolution of acute GA remains unclear; this study was undertaken to evaluate whether IL-37 is involved in spontaneous resolution of AGA. A total of 45 acute GA (AGA),29 non-acute GA (NAGA) male patients and 82 male health control (HC) were involved in this study, we measured IL-7 expression in the peripheral blood mononuclear cells (PBMCs), together with levels of IL-1β, IL-6, IL-10, TNF-α and TGF-β1 in the serum. Further, we either inhibited IL-37 expression in human PBMCs with siRNA or over-expressed the cytokine in human macrophages. Pro-inflammatory cytokine IL-1β, IL-6, and TNF-α expressions were significantly higher in the AGA group than in the NAGA or HC group (P < 0.05, respectively). However, anti-inflammatory IL-37, TGF-β1, and IL-10 were greater in the NAGA group than in the AGA and HC groups (P < 0.05, respectively). Expression of IL-37 in MSU crystal-treated macrophages inhibited the expression of pro-inflammatory cytokines, whereas the abundance of these cytokines increased with silencing of endogenous IL-37 in human blood cells. However, anti-inflammatory TGF-β1 and IL-10 expressions in these supernatants were unaffected by over-expression or knockdown of IL-37. Our study indicates that IL-37 is an important anti-inflammatory cytokine in AGA by suppressing the production of pro-inflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of GA.

  3. Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment.

    PubMed

    Wang, LianLian; Qi, HongBo; Baker, Philip N; Zhen, QianNa; Zeng, Qing; Shi, Rui; Tong, Chao; Ge, Qian

    2017-03-01

    BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15-40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. MATERIAL AND METHODS We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50-100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. RESULTS CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93-1.95) vs. 1.08 (0.85-1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. CONCLUSIONS Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.

  4. Burn size determines the inflammatory and hypermetabolic response

    PubMed Central

    Jeschke, Marc G; Mlcak, Ronald P; Finnerty, Celeste C; Norbury, William B; Gauglitz, Gerd G; Kulp, Gabriela A; Herndon, David N

    2007-01-01

    Background Increased burn size leads to increased mortality of burned patients. Whether mortality is due to inflammation, hypermetabolism or other pathophysiologic contributing factors is not entirely determined. The purpose of the present study was to determine in a large prospective clinical trial whether different burn sizes are associated with differences in inflammation, body composition, protein synthesis, or organ function. Methods Pediatric burned patients were divided into four burn size groups: <40% total body surface area (TBSA) burn, 40–59% TBSA burn, 60–79% TBSA burn, and >80% TBSA burn. Demographic and clinical data, hypermetabolism, the inflammatory response, body composition, the muscle protein net balance, serum and urine hormones and proteins, and cardiac function and changes in liver size were determined. Results One hundred and eighty-nine pediatric patients of similar age and gender distribution were included in the study (<40% TBSA burn, n = 43; 40–59% TBSA burn, n = 79; 60–79% TBSA burn, n = 46; >80% TBSA burn, n = 21). Patients with larger burns had more operations, a greater incidence of infections and sepsis, and higher mortality rates compared with the other groups (P < 0.05). The percentage predicted resting energy expenditure was highest in the >80% TBSA group, followed by the 60–79% TBSA burn group (P < 0.05). Children with >80% burns lost the most body weight, lean body mass, muscle protein and bone mineral content (P < 0.05). The urine cortisol concentration was highest in the 80–99% and 60–79% TBSA burn groups, associated with significant myocardial depression and increased change in liver size (P < 0.05). The cytokine profile showed distinct differences in expression of IL-8, TNF, IL-6, IL-12p70, monocyte chemoattractant protein-1 and granulocyte–macrophage colony-stimulating factor (P < 0.05). Conclusion Morbidity and mortality in burned patients is burn size dependent, starts at a 60% TBSA burn and is due to an

  5. Endocannabinoids and inflammatory response in periodontal ligament cells.

    PubMed

    Özdemir, Burcu; Shi, Bin; Bantleon, Hans Peter; Moritz, Andreas; Rausch-Fan, Xiaohui; Andrukhov, Oleh

    2014-01-01

    Endocannabinoids are associated with multiple regulatory functions in several tissues. The main endocannabinoids, anandamide (AEA) and 2-arachidonylglycerol (2-AG), have been detected in the gingival crevicular fluid of periodontitis patients, but the association between periodontal disease or human periodontal ligament cells (hPdLCs) and endocannabinoids still remain unclear. The aim of the present study was to examine the effects of AEA and 2-AG on the proliferation/viability and cytokine/chemokine production of hPdLCs in the presence/absence of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS). The proliferation/viability of hPdLCs was measured using 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT)-assay. Interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) levels were examined at gene expression and protein level by real-time PCR and ELISA, respectively. AEA and 2-AG did not reveal any significant effects on proliferation/viability of hPdLCs in the absence of P. gingivalis LPS. However, hPdLCs viability was significantly increased by 10-20 µM AEA in the presence of P. gingivalis LPS (1 µg/ml). In the absence of P. gingivalis LPS, AEA and 2-AG did not exhibit any significant effect on the expression of IL-8 and MCP-1 expression in hPdLCs, whereas IL-6 expression was slightly enhanced by 10 µM 2-AG and not affected by AEA. In P.gingivalis LPS stimulated hPdLCs, 10 µM AEA down-regulated gene-expression and protein production of IL-6, IL-8, and MCP-1. In contrast, 10 µM 2-AG had an opposite effect and induced a significant up-regulation of gene and protein expression of IL-6 and IL-8 (P<0.05) as well as gene-expression of MCP-1 in P. gingivalis LPS stimulated hPdLCs. Our data suggest that AEA appears to have an anti-inflammatory and immune suppressive effect on hPdLCs' host response to P.gingivalis LPS, whereas 2-AG appears to promote detrimental inflammatory processes. In conclusion, AEA and 2

  6. Helicobacter hepaticus Induces an Inflammatory Response in Primary Human Hepatocytes

    PubMed Central

    Kleine, Moritz; Worbs, Tim; Schrem, Harald; Vondran, Florian W. R.; Kaltenborn, Alexander; Klempnauer, Jürgen; Förster, Reinhold; Josenhans, Christine; Suerbaum, Sebastian; Bektas, Hüseyin

    2014-01-01

    Helicobacter spp. on human liver cells, resulting in an inflammatory response with increased synthesis of inflammatory mediators and consecutive monocyte activation. PMID:24932686

  7. Helicobacter hepaticus induces an inflammatory response in primary human hepatocytes.

    PubMed

    Kleine, Moritz; Worbs, Tim; Schrem, Harald; Vondran, Florian W R; Kaltenborn, Alexander; Klempnauer, Jürgen; Förster, Reinhold; Josenhans, Christine; Suerbaum, Sebastian; Bektas, Hüseyin

    2014-01-01

    Helicobacter spp. on human liver cells, resulting in an inflammatory response with increased synthesis of inflammatory mediators and consecutive monocyte activation.

  8. Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis.

    PubMed

    Masterson, Joanne C; McNamee, Eóin N; Fillon, Sophie A; Hosford, Lindsay; Harris, Rachel; Fernando, Shahan D; Jedlicka, Paul; Iwamoto, Ryo; Jacobsen, Elizabeth; Protheroe, Cheryl; Eltzschig, Holger K; Colgan, Sean P; Arita, Makoto; Lee, James J; Furuta, Glenn T

    2015-08-01

    Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators. Published by the BMJ Publishing

  9. Associations of Amylin with Inflammatory Markers and Metabolic Syndrome in Apparently Healthy Chinese

    PubMed Central

    Li, Zongmeng; Mou, Haiwei; Yu, Zhijie; Li, Huaixing; Jiang, Peizhen; Yu, Danxia; Wu, Hongyu; Ye, Xingwang; Lin, Xu; Le, Yingying

    2011-01-01

    Background Cellular and animal studies implicate multiple roles of amylin in regulating insulin action, glucose and lipid metabolisms. However, the role of amylin in obesity related metabolic disorders has not been thoroughly investigated in humans. Therefore, we aimed to evaluate the distribution of circulating amylin and its association with metabolic syndrome (MetS) and explore if this association is influenced by obesity, inflammatory markers or insulin resistance in apparently healthy Chinese. Methods A population-based sample of 1,011 Chinese men and women aged 35–54 years was employed to measure plasma amylin, inflammatory markers (C-reactive protein [CRP] and interleukin-6 [IL-6]), insulin, glucose and lipid profiles. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. Results Plasma amylin concentrations were higher in overweight/obese participants than normal-weight counterparts (P<0.001) without sex difference. Circulating amylin was positively associated with CRP, IL-6, BMI, waist circumference, blood pressure, fasting glucose, insulin, amylin/insulin ratio, HOMA-IR, LDL cholesterol and triglycerides, while negatively associated with HDL cholesterol (all P<0.001). After multiple adjustments, the risk of MetS was significantly higher (odds ratio 3.71; 95% confidence interval: 2.53 to 5.46) comparing the highest with the lowest amylin quartile. The association remained significant even further controlling for BMI, inflammatory markers, insulin or HOMA-IR. Conclusions Our study suggests that amylin is strongly associated with inflammatory markers and MetS. The amylin-MetS association is independent of established risk factors of MetS, including obesity, inflammatory markers and insulin resistance. The causal role of hyperamylinemia in the development of MetS needs to be confirmed prospectively. PMID:21935471

  10. Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response.

    PubMed

    Bingyang, J; Jinping, L; Mingzheng, L; Guyan, W; Zhengyi, F

    2007-08-01

    Cardiac surgery in patients undergoing cardiopulmonary bypass (CPB) provokes a vigorous inflammatory response with substantial clinical implications. Once the inflammatory response is triggered by CPB, leukocytes and platelets are activated by multiple stimuli. The administration of a urinary trypsin inhibitor (ulinastatin) during CPB is hypothesized to reduce cytokine release and platelet activation and to decrease pulmonary injury. We performed a prospective randomized study to investigate the influence of high-dose ulinastatin on cytokines and platelet activation and on respiratory function during and after CPB. In this pilot, prospective, randomized and double-blinded study, 30 first-time three-vessel coronary artery disease (CAD) patients undergoing coronary artery bypass graft (CABG) were randomly divided into 2 groups: U group (n=15) received a total dose of 1000000 U ulinastatin and C group (n=15) received placebo. Blood samples were withdrawn from the central vein to measure polymorphonuclear neutrophil elastase (PMNE), tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) and interleukin-8 (IL-8), before induction, 30 min following clamping (T2), reperfusion 3 h (T3), reperfusion 6 h (T4) and reperfusion 12 h (T5). Whole blood samples were taken for CD62P immediately before induction (as baseline), at the end of CPB (before protamine administration), 1 h after heparin neutralization by protamine and 24 h after the operation. In addition, alveolo-arterial oxygen difference (A-aDO(2)) in pulmonary gas exchange function was calculated by obtaining arterial blood gas samples before and after CPB. There were no differences in preoperative parameters between the groups. After CPB, the levels of PMNE, TNF-alfa, IL-6 and IL-8 increased in both groups over baseline values (P<0.01). The levels of PMNE, TNF-alfa, IL-6 and IL-8 in U group were significantly lower than those in C group (P<0.05). No significant differences in CD62p expression between the 2 groups

  11. Prolotherapy Induces an Inflammatory Response in Human Tenocytes In Vitro.

    PubMed

    Ekwueme, Emmanuel C; Mohiuddin, Mahir; Yarborough, Jazmin A; Brolinson, P Gunnar; Docheva, Denitsa; Fernandes, Hugo A M; Freeman, Joseph W

    2017-08-01

    . Furthermore, using a reporter cell line for transforming growth factor-β (TGF-β), a prominent antiinflammatory marker, we showed that treatments led to decreased TGF-β bioactivity. Analysis of soluble proteins using ELISA revealed elevated levels of soluble prostaglandin E2 (PGE2), a prominent inducer of inflammation. Finally, both solutions led to decreased cellular migration in the tenocytes. Taken together, these results suggest that prolotherapy, more so with P2G, may work by decreasing cellular function and eliciting an inflammatory response in tenocytes. Additional studies are needed to confirm the cellular signaling mechanisms involved and the resulting immediate response in vivo. If these preliminary in vitro findings can be confirmed in an in vivo model, they may provide clues for a possible cellular mechanism of a common alternative treatment method currently used for certain soft tissue injuries.

  12. The Acute Exercise-Induced Inflammatory Response: A Comparison of Young-Adult Smokers and Nonsmokers

    ERIC Educational Resources Information Center

    Kastelein, Tegan E.; Donges, Cheyne E.; Mendham, Amy E.; Duffield, Rob

    2017-01-01

    Purpose: This study examined postexercise inflammatory and leukocyte responses in smokers and nonsmokers, as well as the effects of cigarette smoking on the acute postexercise inflammatory and leukocyte response in habitual smokers. Method: Eleven recreationally active male smokers and 11 nonsmokers matched for age and aerobic fitness were…

  13. Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants.

    PubMed

    Colafrancesco, Serena; Perricone, Carlo; Tomljenovic, Lucija; Shoenfeld, Yehuda

    2013-10-01

    Post-vaccination autoimmune phenomena are a major facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and different vaccines, including HPV, have been identified as possible causes. The medical history of three young women who presented with secondary amenorrhea following HPV vaccination was collected. Data regarding type of vaccine, number of vaccination, personal, clinical and serological features, as well as response to treatments were analyzed. All three patients developed secondary amenorrhea following HPV vaccinations, which did not resolve upon treatment with hormone replacement therapies. In all three cases sexual development was normal and genetic screen revealed no pertinent abnormalities (i.e., Turner's syndrome, Fragile X test were all negative). Serological evaluations showed low levels of estradiol and increased FSH and LH and in two cases, specific auto-antibodies were detected (antiovarian and anti thyroid), suggesting that the HPV vaccine triggered an autoimmune response. Pelvic ultrasound did not reveal any abnormalities in any of the three cases. All three patients experienced a range of common non-specific post-vaccine symptoms including nausea, headache, sleep disturbances, arthralgia and a range of cognitive and psychiatric disturbances. According to these clinical features, a diagnosis of primary ovarian failure (POF) was determined which also fulfilled the required criteria for the ASIA syndrome. We documented here the evidence of the potential of the HPV vaccine to trigger a life-disabling autoimmune condition. The increasing number of similar reports of post HPV vaccine-linked autoimmunity and the uncertainty of long-term clinical benefits of HPV vaccination are a matter of public health that warrants further rigorous inquiry. © 2013 John Wiley & Sons Ltd.

  14. A Pro-Inflammatory Role for Nuclear Factor Kappa B in Childhood Obstructive Sleep Apnea Syndrome

    PubMed Central

    Israel, Lee P.; Benharoch, Daniel; Gopas, Jacob; Goldbart, Aviv D.

    2013-01-01

    Study Objectives: Childhood obstructive sleep apnea syndrome (OSAS) is associated with an elevation of inflammatory markers such as C-reactive protein (CRP) that correlates with specific morbidities and subsides following intervention. In adults, OSAS is associated with activation of the transcription factor nuclear factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation, based on the hypothesis that specific NF-kB signaling is activated in children with OSAS. Design: Adenoid and tonsillar tissues from children with OSAS and matched controls were immunostained against NF-kB classical (p65 and p50) and alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines: interleukin (IL)- 1α, IL-1β, tumor necrosis factor-α, and IL-8). Serum CRP levels were measured in all subjects. NF-kB induction was evaluated by a luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and in Jurkat cells with inducible NF-kB expression. p65 translocation to the nucleus, reflecting NF-kB activation, was measured in cells expressing fluorescent NF-kB-p65-GFP (green fluorescent protein). Setting: Sleep research laboratory. Patients or Participants: Twenty-five children with OSAS and 24 without OSAS. Interventions: N/A. Measurements and Results: Higher expression of IL-1α and classical NF-kB subunits p65 and p50 was observed in adenoids and tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured by a luciferase-NF-kB reporter assay and by induction of p65 nuclear translocation in cells permanently transfected with GFP-p65 plasmid. IL-1β showed increased epithelial expression in OSAS tissues. Conclusions: Nuclear factor kappa B is locally and systemically activated in children with obstructive sleep apnea syndrome. This observation may motivate the search for new anti-inflammatory strategies for controlling nuclear factor kappa B activation in obstructive sleep apnea syndrome. Citation: Israel LP

  15. Effects of Blood Products on Inflammatory Response in Endothelial Cells In Vitro

    PubMed Central

    Buddeberg, Felix; Schuppli, Caroline; Roth Z'graggen, Birgit; Hasler, Melanie; Schanz, Urs; Mehr, Manuela; Spahn, Donat R.; Beck Schimmer, Beatrice

    2012-01-01

    Background Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products. Methods The inflammatory response from pre-activated (endotoxin-stimulated) and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC), platelet concentrates (PC) and fresh frozen plasma (FFP) was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated. Results Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product. Conclusion Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells. PMID:22438924

  16. The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

    PubMed Central

    Byeon, Se Eun; Yi, Young-Su; Oh, Jueun; Yoo, Byong Chul; Hong, Sungyoul; Cho, Jae Youl

    2012-01-01

    Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases. PMID:23209344

  17. Perinatal Systemic Inflammatory Response Syndrome and Retinopathy of Prematurity

    PubMed Central

    Sood, Beena G.; Madan, Ashima; Saha, Shampa; Schendel, Diana; Thorsen, Poul; Skogstrand, Kristin; Hougaard, David; Shankaran, Seetha; Carlo, Wally

    2010-01-01

    Fetal and neonatal inflammation is associated with several morbidities of prematurity. Its relationship to retinopathy of prematurity (ROP) has not been investigated. Our objective was to determine the relationship between cytokine levels and ROP in the first three postnatal weeks. Data for this study were derived from the NICHD Cytokine Study. Dried blood spots were obtained from infants <1000g on days 0-1, 3±1, 7±2, 14±3, and 21±3. Infants were classified into three groups – No, Mild, and Severe ROP. Multiplex Luminex assay was used to quantify 20 cytokines. Temporal profiles of cytokines were evaluated using mixed effects models after controlling for covariates. Of 1074 infants enrolled, 890 were examined for ROP and 877 included in the analysis. ROP was associated with several clinical characteristics on unadjusted analyses. Eight cytokines remained significantly different across ROP groups in adjusted analyses. IL-6 and IL-17 showed significant effects in early time periods (D0-3); TGF-β, brain derived neurotrophic factor (BDNF), and regulated upon activation, normal T cell expressed and secreted (RANTES) in later time periods (D7-21) and IL-18, C-reactive protein (CRP) and neurotrophin-4 (NT-4) in both early and later time periods. We conclude that perinatal inflammation may be involved in the pathogenesis of ROP. PMID:20032809

  18. High Intensity Interval Training Reduces the Levels of Serum Inflammatory Cytokine on Women with Metabolic Syndrome.

    PubMed

    Steckling, F M; Farinha, J B; Santos, D L D; Bresciani, G; Mortari, J A; Stefanello, S T; Courtes, A A; Duarte, T; Duarte, M M M F; Moresco, R N; Cardoso, M S; Soares, F A A

    2016-11-01

    Objectives: This study investigate the effects of a high intensity interval training (HIIT) and 2 weeks of detraining in functional and body composition parameters, lipoproteins, glucose metabolismand inflammation markers in postmenopausal women with metabolic syndrome (MS). Design: 17 untrained women with MS underwent a HIIT program for 12 weeks. Methods: The training was performed in treadmills, 3 days per week, with intensity ranging from 70-90% of the maximum heart rate (HRmax) and 2 weeks untrained (inactive). Functional and body composition parameters were evaluated before and after the training, while maximal oxygen uptake, lipoprotein and inflammation markers were analyzed before, after training and also in detraining. Results: The HITT program resulted in changesparameters as glucose, HbA1cand NOx after training. In addition, a reduction in pro-inflammatory interleukins and an increase in IL-10 after the HIIT program were found. However, an increase in plasma levels of lipoprotein was found and body composition parameters remain unaltered.Besides, only 2 weeks of detraining are able to revert the effects on inflammatory parameters afforded by the HIIT program. Conclusions: The HIIT program used here positively affected inflammatory profile and other parameters, as glucose, HbA1cand NOx, on postmenopausal women with MS. Moreover, 2 weeks of detraining can reverse the beneficial effects of HIIT program. Our results point out the necessity to aply acontinuous HITT program, in order maintain the benefits detected, to post menopausal women with MS.

  19. Elevated Circulating Levels of Inflammatory Markers in Patients with Acute Coronary Syndrome

    PubMed Central

    Al Shahi, Hamad; Shimada, Kazunori; Miyauchi, Katsumi; Yoshihara, Takuma; Sai, Eiryu; Shiozawa, Tomoyuki; Naito, Ryo; Aikawa, Tatsuro; Ouchi, Shohei; Kadoguchi, Tomoyasu; Miyazaki, Tetsuro; Daida, Hiroyuki

    2015-01-01

    Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs) in patients with either acute coronary syndrome (ACS) or stable coronary artery disease (CAD). Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2 and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P < 0.05). In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P < 0.05). The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients. PMID:26504600

  20. Enhanced natural killer activity and production of pro-inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax).

    PubMed

    Castoldi, Lindsey; Golim, Marjorie Assis; Filho, Orlando Garcia Ribeiro; Romagnoli, Graziela Gorete; Ibañez, Olga Célia Martinez; Kaneno, Ramon

    2007-03-01

    Strains of mice with maximal and minimal acute inflammatory responsiveness (AIRmax and AIRmin, respectively) were developed through selective breeding based on their high- or low-acute inflammatory responsiveness. Previous reports have shown that AIRmax mice are more resistant to the development of a variety of tumours than AIRmin mice, including spontaneous metastasis of murine melanoma. Natural killer activity is involved in immunosurveillance against tumour development, so we analysed the number and activity of natural killer cells (CD49b(+)), T-lymphocyte subsets and in vitro cytokine production by spleen cells of normal AIRmax and AIRmin mice. Analysis of lymphocyte subsets by flow cytometry showed that AIRmax mice had a higher relative number of CD49b(+) cells than AIRmin mice, as well as cytolytic activity against Yac.1 target cells. The number of CD3(+) CD8(+) cells was also higher in AIRmax mice. These findings were associated with the ability of spleen cells from AIRmax mice in vitro to produce higher levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin-12p40 and interferon-gamma but not the anti-inflammatory interleukin-10. Taken together, our data suggest that the selective breeding to achieve the AIRmax and AIRmin strains was able to polarize the genes associated with cytotoxic activity, which can be responsible for the antitumour resistance observed in AIRmax mice.

  1. Validation of the Auto-Inflammatory Diseases Activity Index (AIDAI) for hereditary recurrent fever syndromes

    PubMed Central

    Piram, Maryam; Koné-Paut, Isabelle; Lachmann, Helen J; Frenkel, Joost; Ozen, Seza; Kuemmerle-Deschner, Jasmin; Stojanov, Silvia; Simon, Anna; Finetti, Martina; Sormani, Maria Pia; Martini, Alberto; Gattorno, Marco; Ruperto, Nicolino

    2014-01-01

    Objectives To validate the Auto-Inflammatory Diseases Activity Index (AIDAI) in the four major hereditary recurrent fever syndromes (HRFs): familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndromes (CAPS). Methods In 2010, an international collaboration established the content of a disease activity tool for HRFs. Patients completed a 1-month prospective diary with 12 yes/no items before a clinical appointment during which their physician assessed their disease activity by a questionnaire. Eight international experts in auto-inflammatory diseases evaluated the patient's disease activity by a blinded web evaluation and a nominal group technique consensus conference, with their consensus judgement considered the gold standard. Sensitivity/specificity/accuracy measures and the ability of the score to discriminate active from inactive patients via the best cut-off score were calculated by a receiver operating characteristic analysis. Results Consensus was achieved for 98/106 (92%) cases (39 FMF, 35 CAPS, 14 TRAPS and 10 MKD), with 26 patients declared as having inactive disease and 72 as having active disease. The median total AIDAI score was 14 (range=0–175). An AIDAI cut-off score ≥9 discriminated active from inactive patients, with sensitivity/specificity/accuracy of 89%/92%/90%, respectively, and an area under the curve of 98% (95% CI 96% to 100%). Conclusions The AIDAI score is a valid and simple tool for assessing disease activity in FMF/MKD/TRAPS/CAPS. This tool is easy to use in clinical practice and has the potential to be used as the standard efficacy measure in future clinical trials. PMID:24026675

  2. Lactic acid delays the inflammatory response of human monocytes

    SciTech Connect

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

  3. Lactic acid delays the inflammatory response of human monocytes.

    PubMed

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Dimethyl Fumarate Reduces Inflammatory Responses in Experimental Colitis

    PubMed Central

    Casili, Giovanna; Cordaro, Marika; Impellizzeri, Daniela; Bruschetta, Giuseppe; Paterniti, Irene; Cuzzocrea, Salvatore

    2016-01-01

    Background and Aims: Fumaric acid esters have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis. We aimed to develop a new treatment for colitis. Methods: We investigated the effect of dimethylfumarate [DMF, 10-30-100mg/kg] on an experimental model of colitis induced by dinitrobenzene sulphuric acid [DNBS]. We also evaluated the therapeutic activity of 7 weeks’ treatment with DMF [30mg/kg] on 9-week-old IL-10KO mice that spontaneously develop a T helper-1 [Th1]-dependent chronic enterocolitis after birth, that is fully established at 8–10 weeks of age. The mechanism of this pharmacological potential of DMF [10 μM] was investigated in colonic epithelial cell monolayers [Caco-2] exposed to H2O2. The barrier function was evaluated by the tight junction proteins. Results: The treatment with DMF significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. DMF [30 and 100mg/kg] also caused a substantial reduction in the degree of colon injury, in the rise in myeloperoxidase [MPO] activity, and in the increase in tumour necrosis factor [TNF]-α expression, as well as in the up-regulation of ICAM-1 caused by DNBS in the colon. Molecular studies demonstrated that DMF impaired NF-κB signalling via reduced p65 nuclear translocalisation. DMF induced a stronger antioxidant response as evidenced by a higher expression of Mn-superoxide dismutase. Moreover, DMF protected human intestinal epithelial cells against H2O2-induced barrier dysfunction, restoring ZO-1 occludin expression, via the HO-1 pathway. Conclusions: DMF treatment reduces the degree of colitis caused by DNBS. We propose that DMF treatment may be useful in the treatment of inflammatory bowel disease. PMID:26690241

  5. Response shift and disease activity in inflammatory bowel disease.

    PubMed

    Lix, Lisa M; Chan, Eric K H; Sawatzky, Richard; Sajobi, Tolulope T; Liu, Juxin; Hopman, Wilma; Mayo, Nancy

    2016-07-01

    Response shift (RS) may mask true change in health-related quality of life in longitudinal studies. People with chronic conditions may experience RS as they adapt to their disease, but it is unknown whether fluctuations in disease activity will influence the presence of RS. The study purpose was to test for RS in individuals with inflammatory bowel disease (IBD), a condition characterized by periods of symptom flares and remission. Data were from the Manitoba IBD Cohort Study (N = 388). Multi-group confirmatory factor analysis (MG-CFA) and a RS detection method based on structural equation modeling were used to test for reconceptualization, reprioritization, and recalibration RS in participants with consistent active, consistent inactive, and inconsistent disease activity over a 6-month period on the SF-36. The MG-CFA revealed that a weak invariance model with equal factor loadings across groups was the best fit to the baseline SF-36 data. Reconceptualization, uniform recalibration, and non-uniform recalibration RS was detected in the consistent active group, but effect sizes were small. For the consistent inactive group, recalibration RS was observed and effect sizes were small to moderate. For the inconsistent disease activity group, small-to-moderate recalibration RS effects were observed. There was no evidence of reprioritization. Individuals with a chronic disease may exhibit RS even if they are not actively experiencing symptoms on a consistent basis. Heterogeneity in the type and magnitude of RS effects may be observed in chronic disease patients who experience changes in disease symptoms.

  6. Prokineticin 1 Induces Inflammatory Response in Human Myometrium

    PubMed Central

    Gorowiec, Marta R.; Catalano, Rob D.; Norman, Jane E.; Denison, Fiona C.; Jabbour, Henry N.

    2011-01-01

    The infiltration of human myometrium and cervix with leukocytes and the formation of a pro-inflammatory environment within the uterus have been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labor. The expression of PROK1 receptor remains unchanged during labor and is abundantly expressed in the myometrium. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines, including IL-1β, chemokine C-C motif ligand 3, and colony-stimulating factor 3. In addition, we demonstrate that PROK1 increases the expression of chemokine C-C motif ligand 20, IL-6, IL-8, prostaglandin synthase 2, and prostaglandin E2 and F2α secretion. The treatment of myometrial explants with 100 ng/mL of lipopolysaccharide up-regulates the expression of PROK1, PROK1 receptor, and inflammatory mediators. The infection of myometrial explants with lentiviral microRNA targeting PROK1, preceding treatment with lipopolysaccharide, reduces the expression of inflammatory genes. We propose that PROK1 is a novel inflammatory mediator that can contribute to the onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection. PMID:21983634

  7. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system

    PubMed Central

    Dilger, Ryan N.; Johnson, Rodney W.

    2008-01-01

    Recent studies suggest that activation of the peripheral immune system elicits a discordant central (i.e., in the brain) inflammatory response in aged but otherwise healthy subjects compared with younger cohorts. A fundamental difference in the reactive state of microglial cells in the aged brain has been suggested as the basis for this discordant inflammatory response. Thus, the aging process appears to serve as a “priming” stimulus for microglia, and upon secondary stimulation with a triggering stimulus (i.e., peripheral signals communicating infection), these primed microglia release excessive quantities of proinflammatory cytokines. Subsequently, this exaggerated cytokine release elicits exaggerated behavioral changes including anorexia, hypersomnia, lethargy, decreased social interaction, and deficits in cognitive and motor function (collectively known as the sickness behavior syndrome). Whereas this reorganization of host priorities is normally adaptive in young subjects, there is a propensity for this response to be maladaptive in aged subjects, resulting in greater severity and duration of the sickness behavior syndrome. Consequently, acute bouts of cognitive impairment in elderly subjects increase the likelihood of poor self-care behaviors (i.e., anorexia, weight loss, noncompliance), which ultimately leads to higher rates of hospitalization and mortality. PMID:18495785

  8. Effects of Acupuncture Knife on Inflammatory Factors and Pain in Third Lumbar Vertebrae Transverse Process Syndrome Model Rats

    PubMed Central

    Yu, Jia Ni; Guo, Chang Qing; Hu, Bo; Liu, Nai Gang; Sun, Hong Mei; Xu, Hong; Wu, Hai Xia; Guo, Yan; Liang, Chu Xi; Chen, Zhan Xia; Li, Xiao Hong

    2014-01-01

    The aim of this paper was to explore the long-term effects and pain relief mechanism of acupuncture knife on third lumbar vertebrae (L3) transverse process syndrome. Forty SD rats were randomized into control, model, electroacupuncture (EA), and acupuncture knife (AK) group. Except control rats, other rats were subjected to an operation to emulate L3 transverse process syndrome. Fourteen days after the operation, EA and AK rats were given electroacupuncture and acupuncture knife treatments, respectively. Fifty-six days after the operation, enzyme-linked immunosorbent assay was used to measure substance P (SP), 5-hydroxytryptamine (5-HT), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) in peripheral blood. The tail flick test was used to observe pain threshold. We found that rats with the simulation operation had significantly higher levels of SP, 5-HT, IL-1, IL-10, TNF-α, and TGF-β, while the AK rats had lower levels. In addition, the pain threshold of AK rats was similar to that of control rats. AK pretreatment could alleviate pain through modulating inflammatory response. PMID:25544854

  9. Comparison of the Cytokine and Chemokine Dynamics of the Early Inflammatory Response in Models of Burn Injury and Infection

    PubMed Central

    Orman, Mehmet A.; Nguyen, Tung T.; Ierapetritou, Marianthi G.; Berthiaume, Francois; Androulakis, Ioannis P.

    2011-01-01

    The inflammatory response, and its subsequent resolution, are the result of a very complex cascade of events originating at the site of injury or infection. When the response is severe and persistent, Systemic Inflammatory Response Syndrome can set in, which is associated with a severely debilitating systemic hypercatabolic state. This complex behavior, mediated by cytokines and chemokines, needs to be further explored to better understand its systems properties and potentially identify multiple targets that could be addressed simultaneously. In this context, short term responses of serum cytokines and chemokines were analyzed in two types of insults: rats receiving a “sterile” cutaneous dorsal burn on 20% of the total body surface area (TBSA); rats receiving a cecum ligation and puncture treatment (CLP) to induce infection. Considering the temporal variability observed in the baseline corresponding to the control group, the concept of area under the curve (AUC) was explored to assess the dynamic responses of cytokines and chemokines. MCP-1, GROK/KC, IL-12, IL-18 and IL-10 were observed in both burn and CLP groups. While IL-10 concentration was only increased in the burn group, Eotaxin was only elevated in CLP group. It was also observed that Leptin and IP-1 concentrations were decreased in both CLP and sham-CLP groups. The link between the circulating protein mediators and putative transcription factors regulating the cytokine/chemokine gene expression was explored by searching the promoter regions of cytokine/chemokine genes in order to characterize and differentiate the inflammatory responses based on the dynamic data. Integrating multiple sources together with the bioinformatics tools identified mediators sensitive to type and extent of injury, and provided putative regulatory mechanisms. This is essential to gain a better understanding for the important regulatory points that can be used to modulate the inflammatory state at molecular level. PMID:21652218

  10. IL-37 suppresses MyD88-mediated inflammatory responses in human aortic valve interstitial cells.

    PubMed

    Zhan, Qiong; Zeng, Qingchun; Song, Rui; Zhai, Yufeng; Xu, Dingli; Fullerton, David A; Dinarello, Charles A; Meng, Xianzhong

    2017-03-27

    Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulati