A metabolomics and mouse models approach to study inflammatory and immune responses to radiation

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

Fornace, Albert J.; Li, Henghong

2013-12-02

The three-year project entitled "A Metabolomics and Mouse Models Approach to Study Inflammatory and Immune Responses to Radiation" was initiated in September 2009. The overall objectives of this project were to investigate the acute and persistent effects of low dose radiation on T cell lymphocyte function and physiology, as well the contributions of these cells to radiation-induced inflammatory responses. Inflammation after ionizing radiation (IR), even at low doses, may impact a variety of disease processes, including infectious disease, cardiovascular disease, cancer, and other potentially inflammatory disorders. There were three overall specific aims: 1. To investigate acute and persistent effects ofmore » low dose radiation on T cell subsets and function; 2. A genetic approach with mouse models to investigate p38 MAPK pathways that are involved in radiation-induced inflammatory signaling; 3. To investigate the effect of radiation quality on the inflammatory response. We have completed the work proposed in these aims.« less

Peripheral nerve proteins as potential autoantigens in acute and chronic inflammatory demyelinating polyneuropathies.

PubMed

Lim, Jia Pei; Devaux, Jérôme; Yuki, Nobuhiro

2014-10-01

Guillain-Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies. Copyright © 2014 Elsevier B.V. All rights reserved.

Acute inflammatory neuropathy with monoclonal anti-GM2 IgM antibodies, IgM-κ paraprotein and additional autoimmune processes in association with a diffuse large B-cell non-Hodgkin's lymphoma.

PubMed

Milnik, Annette; Roggenbuck, Dirk; Conrad, Karsten; Bartels, Claudius

2013-01-21

Lymphoproliferative disorders are often associated with autoimmune processes preceding or following the occurrence of a lymphoma. Here, we describe a patient with a history of recurrent diffuse large B-cell non-Hodgkin's lymphoma who suffered from an acute inflammatory neuropathy with specific monoclonal anti-GM2 IgM antibodies and associated IgM-κ paraprotein. It was possible in this case to prove that both, anti-GM2 IgM antibodies and IgM-κ paraprotein, share the same binding characteristic. In addition, the patient possibly suffered from an immune thrombocytopenia and an early-stage bullous pemphigoid with anti-BP-230 IgG antibodies. Intravenous immunoglobulin and plasmapheresis alleviated the acute neuropathy and thrombocytopenia, while the bullous pemphigoid has been aggravated. In summary, the simultaneous occurrence of multiple autoimmune processes was a sign of a dysfunctional immune system preceding the relapse of a B-cell non-Hodgkin's lymphoma.

Contributions of Neutrophils to Resolution of Mucosal Inflammation

PubMed Central

Colgan, Sean P.; Ehrentraut, Stefan F.; Glover, Louise E.; Kominsky, Douglas J.; Campbell, Eric L.

2014-01-01

Neutrophil (PMN) recruitment from the blood stream into surrounding tissues involves a regulated series of events central to acute responses in host defense. Accumulation of PMN within mucosal tissues have historically been considered pathognomonic features of both acute and chronic inflammatory conditions. Historically PMNs have been deemed necessary but detrimental when recruited, given the potential for tissue damage that results from a variety of mechanisms. Recent work, however, has altered our preconcieved notions of PMN contributions to inflammatory processes. In particular, significant evidence implicates a central role for the PMN in triggering inflammatory resolution. Such mechanisms involve both metabolic and biochemical crosstalk pathways during the intimate interactions of PMN with other cell types at inflammatory sites. Here, we highlight several recent examples of how PMN coordinate the resolution of ongoing inflammation, with a particular focus on the gastrointestinal mucosa. PMID:22968707

Inflammation in acute and chronic pancreatitis.

PubMed

Habtezion, Aida

2015-09-01

This report reviews recent animal model and human studies associated with inflammatory responses in acute and chronic pancreatitis. Animal model and limited human acute and chronic pancreatitis studies unravel the dynamic nature of the inflammatory processes and the ability of the immune cells to sense danger and environmental signals. In acute pancreatitis, such molecules include pathogen-associated molecular pattern recognition receptors such as toll-like receptors, and the more recently appreciated damage-associated molecular pattern molecules or 'alarmin' high mobility group box 1 and IL-33. In chronic pancreatitis, a recent understanding of a critical role for macrophage-pancreatic stellate cell interaction offers a potential targetable pathway that can alter fibrogenesis. Microbiome research in pancreatitis is a new field gaining interest but will require further investigation. Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression.

Integrating microRNAs into a system biology approach to acute lung injury.

PubMed

Zhou, Tong; Garcia, Joe G N; Zhang, Wei

2011-04-01

Acute lung injury (ALI), including the ventilator-induced lung injury (VILI) and the more severe acute respiratory distress syndrome (ARDS), are common and complex inflammatory lung diseases potentially affected by various genetic and nongenetic factors. Using the candidate gene approach, genetic variants associated with immune response and inflammatory pathways have been identified and implicated in ALI. Because gene expression is an intermediate phenotype that resides between the DNA sequence variation and the higher level cellular or whole-body phenotypes, the illustration of gene expression regulatory networks potentially could enhance understanding of disease susceptibility and the development of inflammatory lung syndromes. MicroRNAs (miRNAs) have emerged as a novel class of gene regulators that play critical roles in complex diseases including ALI. Comparisons of global miRNA profiles in animal models of ALI and VILI identified several miRNAs (eg, miR-146a and miR-155) previously implicated in immune response and inflammatory pathways. Therefore, via regulation of target genes in these biological processes and pathways, miRNAs potentially contribute to the development of ALI. Although this line of inquiry exists at a nascent stage, miRNAs have the potential to be critical components of a comprehensive model for inflammatory lung disease built by a systems biology approach that integrates genetic, genomic, proteomic, epigenetic as well as environmental stimuli information. Given their particularly recognized role in regulation of immune and inflammatory responses, miRNAs also serve as novel therapeutic targets and biomarkers for ALI/ARDS or VILI, thus facilitating the realization of personalized medicine for individuals with acute inflammatory lung disease. Copyright © 2011 Mosby, Inc. All rights reserved.

Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia.

PubMed

Straub, Rainer H; Cutolo, Maurizio; Pacifici, Roberto

2015-10-01

Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." Extensive literature search in PubMed central. Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. The article highlights the complexity of interwoven pathways of osteopenia. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Evolutionary medicine and bone loss in chronic inflammatory diseases – a theory of inflammation-related osteopenia

PubMed Central

Straub, Rainer H.; Cutolo, Maurizio; Pacifici, Roberto

2015-01-01

Objective Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflammaging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an “accident of inflammation”. Methods Extensive literature search in PubMed central. Results Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. Conclusions The article highlights the complexity of interwoven pathways of osteopenia. PMID:26044543

Anti-inflammatory activity of Arnica montana 6cH: preclinical study in animals.

PubMed

Macêdo, S B; Ferreira, L R; Perazzo, F F; Carvalho, J C

2004-04-01

The anti-inflammatory effect of Arnica montana 6cH was evaluated using acute and chronic inflammation models. In the acute, model, carrageenin-induced rat paw oedema, the group treated with Arnica montana 6cH showed 30% inhibition compared to control (P < 0.05). Treatment with Arnica 6cH, 30 min prior to carrageenin, did not produce any inhibition of the inflammatory process. In the chronic model, Nystatin-induced oedema, the group treated 3 days previously with Arnica montana 6cH had reduced inflammation 6 h after the inflammatory agent was applied (P < 0.05). When treatment was given 6 h after Nystatin treatment, there was no significant inhibitory effect. In a model based on histamine-induced increase of vascular permeability, pretreatment with Arnica montana 6cH blocked the action of histamine in increasing vascular permeability.

Acute and Recurrent Pericarditis.

PubMed

Imazio, Massimo; Gaita, Fiorenzo

2017-11-01

Acute and recurrent pericarditis is the most common pericardial syndrome encountered in clinical practice either as an isolated process or as part of a systemic disease. The diagnosis is based on clinical evaluation, electrocardiogram, and echocardiography. The empiric therapy is based on nonsteroidal anti-inflammatory drugs plus colchicine as first choice, resorting to corticosteroids for specific indications (eg, systemic inflammatory disease on corticosteroids, pregnancy, renal failure, concomitant oral anticoagulants), for contraindications or failure of the first-line therapy. The most common complication is recurrence, occurring in up to 30% of cases after a first episode of pericarditis. Copyright © 2017 Elsevier Inc. All rights reserved.

Viral Heart Disease and Acute Coronary Syndromes - Often or Rare Coexistence?

PubMed

Pawlak, Agnieszka; Wiligorska, Natalia; Wiligorska, Diana; Frontczak-Baniewicz, Malgorzata; Przybylski, Maciej; Krzyzewski, Rafal; Ziemba, Andrzej; Gil, Robert J

2018-01-01

Clinical presentation of viral myocarditis can mimic acute coronary syndrome and making diagnosis of viral heart disease (VHD) may be challenging. The presence of coronary artery disease (CAD) does not always exclude VHD and these entities can coexist. However, the incidence of co-occurrence of CAD and VHD is not precisely known. Moreover, inflammatory process caused by viruses may result in atherosclerotic plaque destabilization. The goal of this work is to summarize the current knowledge about co-occurrence of VHD and CAD. This article presents the importance of inflammatory process in both diseases and helps to understand pathophysiological mechanisms underlying their coexistence. It provides information about making differential diagnosis between these entities, including clinical presentation, noninvasive imaging features and findings in endomyocardial biopsy. Although currently there are no standard therapy strategies in coexistence of VHD and CAD, we present some remarkable aspects of treatment of patients, in whom VHD co-occurs with CAD. Viral heart disease may occur both in patients without and with atherosclerotic plaques in coronary arteries. Destabilization of atherosclerotic plaques in coronary arteries can be facilitated by inflammatory process. Increased inflammatory infiltrates in the coronary lesions of patients with VHD can lead to plaques' instability and consequently trigger acute coronary syndrome. In this article we attempted to present that co-occurrence of VHD and CAD may have therapeutic implications and as specific antiviral treatment is currently available, proper diagnosis and treatment can improve patient's condition and prognosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anti-inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage in an intensive care unit

PubMed Central

Zhou, Xiurong; Chen, Jiafeng; Wang, Chengdong; Wu, Lili

2017-01-01

Intracerebral hemorrhage is one of the most common types of cerebrovascular disease in humans and often causes paralysis, a vegetative state and even death. Patients with acute intracerebral hemorrhage are frequently monitored in intensive care units (ICUs). Spontaneous intracerebral hemorrhage is associated with a higher rate of mortality and morbidity than other intracephalic diseases. The expression levels of inflammatory factors have important roles in inflammatory responses indicative of changes in a patient's condition and are therefore important in the monitoring and treatment of affected patients at the ICU as well as the development of therapeutic strategies for acute cerebral hemorrhage. The present study investigated the anti-inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage at an ICU, and inflammatory factors and cellular changes were systematically analyzed. The plasma concentrations of inflammatory factors, including interleukin (IL)-4, IL-6, IL-8 and IL-10, were evaluated by ELISAs. The plasma concentrations of inflammatory cellular changes were detected by using flow cytometry. The results demonstrated that after Simvastatin treatment of patients with acute cerebral hemorrhage at the ICU, the plasma concentrations of IL-4, IL-6, IL-8 and IL-10 were downregulated compared with those in placebo-treated controls. In addition, Simvastatin treatment at the ICU decreased lymphocytes, granulocytes and mononuclear cells in patients with acute cerebral hemorrhage. The levels of inflammatory factors were associated with brain edema in patients with acute cerebral hemorrhage treated at the ICU. In addition, the amount of bleeding was reduced in parallel with the inflammatory cell plasma concentration of lymphocytes, granulocytes and mononuclear cells. Importantly, Simvastatin treatment produced beneficial outcomes by improving brain edema and reducing the amount of bleeding. In conclusion, the present study demonstrated the efficacy of Simvastatin in treating acute intracerebral hemorrhage and evidenced the association between inflammatory responses and the progress of affected patients at the ICU, thereby providing insight for applying effective therapies for patients with acute intracerebral hemorrhage. PMID:29285177

Inflammatory Cell Infiltrates in Acute and Chronic Thoracic Aortic Dissection.

PubMed

Wu, Darrell; Choi, Justin C; Sameri, Aryan; Minard, Charles G; Coselli, Joseph S; Shen, Ying H; LeMaire, Scott A

2013-12-01

Thoracic aortic dissection (TAD) is a highly lethal cardiovascular disease. Injury to the intima and media allows pulsatile blood to enter the media, leading to dissection formation. Inflammatory cells then infiltrate the site of aortic injury to clear dead cells and damaged tissue. This excessive inflammation may play a role in aneurysm formation after dissection. Using immunohistochemistry, we compared aortic tissues from patients with acute TAD (n = 11), patients with chronic TAD (n = 35), and donor controls (n = 20) for the presence of CD68+ macrophages, neutrophils, mast cells, and CD3+ T lymphocytes. Tissue samples from patients with acute or chronic TAD generally had significantly more inflammatory cells in both the medial and adventitial layers than did the control samples. In tissues from patients with acute TAD, the adventitia had more of the inflammatory cells studied than did the media. The pattern of increase in inflammatory cells was similar in chronic and acute TAD tissues, except for macrophages, which were seen more frequently in the adventitial layer of acute TAD tissue than in the adventitia of chronic TAD tissue. The inflammatory cell content of both acute and chronic TAD tissue was significantly different from that of control tissue. However, the inflammatory cell profile of aneurysmal chronic TAD was similar to that of acute TAD. This may reflect a sustained injury response that contributes to medial degeneration and aneurysm formation.

Anti-inflammatory effects of Citrus sinensis L., Citrus paradisi L. and their combinations.

PubMed

Khan, Rafeeq Alam; Mallick, Neelam; Feroz, Zeeshan

2016-05-01

Citrus bioflavonoids embrace a wide group of phenolic compounds effecting the production and scavenging of reactive oxygen species and the processes relating free radical-mediated injury. Keeping in view of the antioxidant and anti-inflammatory properties of Citrus sinensis and Citrus paradisi, present study was undertaken to explore the effects of C. sinensis (orange juice) and C. paradisi (grapefruit juice) at three different doses alone and their two combinations with the objective to examine the effects of these compounds in an experimental model of rat colitis induced by trinitrobenzenesulphonic acid (TNBS). Hence biochemical parameters e.g. myeloperoxidase, alkaline phosphatase, C-reactive protein (CRP) and glutathione were assessed. Data entry and analysis was accomplished by Statistical Package for the Social Sciences version 17 and was presented as mean ± S.E.M with 95% confidence interval. Present result shows that these juices, mainly C. paradisi, may be efficacious for the management of inflammatory bowel disease. In acute colitis model, C. paradise encouraged a decrease in the extension of the lesion escorted by a decrease in the occurrence of diarrhea and reinstatement of the glutathione content. Related effects were produced by the administration of C. sinensis, which also prevented the myeloperoxidase and alkaline phosphatase actions in acute intestinal inflammatory process. The effect of the citrus juices on the inflammatory process may be associated to their antioxidant and anti-inflammatory properties, as revealed in present investigation. The favorable effects exerted were demonstrated both by histological and biochemical changes and were related with a progress in the colonic oxidative status.

[Cytokine profile in young children with acute stenotic laryngotracheitis].

PubMed

Гладченко, Ольга І; Токарєв, Павло В; Надрага, Олександр Б

2016-01-01

One of the most severe complications of acute respiratory infections in young children is acute stenotic laryngotracheitis (croup). The relationship between cytokine blood levels and symptoms of croup, croup severity, disease sequel, despite numerous studies is still unclear. Cytokine profile in young children with acute stenotic laryngotracheitis investigation. 112 children aged 12 min. - 36 mon. with acute stenotic laryngotracheitis which were treated at the Lviv Regional Infectious Diseases Hospital were kept under observation. Croup symptoms, levels of interleukins (IL1, IL4, IL6, IL10, IL17) in serum, DNA and RNA viruses in respiratory nasal mucus were studied; Chan croup severity was used. In the pathogenesis of croup has an important role the imbalance between inflammatory (IL1, IL6) and anti-inflammatory (IL4, IL10, IL17) cytokines, which does not reduce the intensity of inflammatory reactions and its lead to local swelling, muscle spasm, excessive production of mucus in the place of viral replication. The levels of inflammatory and anti-inflammatory cytokines in the blood serum of children with croup were significantly higher than in patients with acute laryngitis. In patients with recurrent croup, unlike patients with the first case of croup does we don't see a significant correlation between the concentrations of inflammatory and anti-inflammatory cytokine levels Conclusions: The significantly higher levels of cytokines in children with croup compared with the group of patients with acute laryngitis were found, imbalance between anti-inflammatory (IL1, IL6) cytokine levels and inflammatory (IL4, IL10, IL17) cytokine levels in children who developed recurrent croup.

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling

PubMed Central

Dick, Thomas E.; Molkov, Yaroslav I.; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J.; Doyle, John; Scheff, Jeremy D.; Calvano, Steve E.; Androulakis, Ioannis P.; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. PMID:22783197

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

PubMed

Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

The central role of hypothalamic inflammation in the acute illness response and cachexia.

PubMed

Burfeind, Kevin G; Michaelis, Katherine A; Marks, Daniel L

2016-06-01

When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Antioxidant and anti-inflammatory activities of Moroccan Erica arborea L].

PubMed

Amezouar, F; Badri, W; Hsaine, M; Bourhim, N; Fougrach, H

2013-12-01

The present study was carried out to evaluate the antioxidant and anti-inflammatory capacity, and acute toxicity of Moroccan Erica arborea leaves. Antioxidant capacity was assessed by diphenyle-picryl-hydrazyl (DPPH), phosphomolybdate (PPM) and ferric reducing antioxidant power (FRAP) tests and anti-inflammatory capacity was evaluated by hind paw oedema model using carrageenan-induced inflammation in rat. The acute toxicity was evaluated using mice. Acute toxicity of ethanolic extract of E. arborea showed no sign of toxicity at dose of 5 g/kg B.W. Our extracts have important antioxidant properties. The efficient concentration of the ethanolic extract (10.22 μg/ml) required for decreasing initial DPPH concentration by 50% was comparable to that of standard solution butyl-hydroxy-toluene (BHT) (8.87 μg/ml). The administration of ethanolic extract at doses of 200 and 400mg/kg B.W. was able to prevent plantar oedema and exhibited a significant inhibition against carrageenan-induced inflammation when compared to the control group (NaCl 0.9%) but comparable to those of diclofenac (reference drug). Our results show that the leaves of E. arborea may contain some bioactive compounds which are responsible for the antioxidant and anti-inflammatory activities observed here. Our finding may indicate the possibility of using the extracts of this plant to prevent the antioxidant and inflammatory processes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Inflammatory Stroke Extracellular Vesicles Induce Macrophage Activation.

PubMed

Couch, Yvonne; Akbar, Naveed; Davis, Simon; Fischer, Roman; Dickens, Alex M; Neuhaus, Ain A; Burgess, Annette I; Rothwell, Peter M; Buchan, Alastair M

2017-08-01

Extracellular vesicles (EVs) are protein-lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs. EVs were quantified and analyzed in the sera of patients after an acute stroke (<24 hours; OXVASC [Oxford Vascular Study]). Isolated EV fractions were subjected to untargeted proteomic analysis by liquid chromatography mass-spectrometry/mass-spectrometry and then applied to macrophages in culture to investigate inflammatory gene expression. EV number, but not size, is significantly increased in stroke patients when compared to age-matched controls. Proteomic analysis reveals an overall increase in acute phase proteins, including C-reactive protein. EV fractions applied to monocyte-differentiated macrophage cultures induced inflammatory gene expression. Together these data show that EVs from stroke patients are proinflammatory in nature and are capable of inducing inflammation in immune cells. © 2017 American Heart Association, Inc.

Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load.

PubMed

Vazquez, Bruna Perez; Vazquez, Thaís Perez; Miguel, Camila Botelho; Rodrigues, Wellington Francisco; Mendes, Maria Tays; de Oliveira, Carlo José Freire; Chica, Javier Emílio Lazo

2015-04-03

Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain. We used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 10(2)), medium (3 × 10(3)), and high (3 × 10(4)) parasite loads were generated by infecting C57BL/6 mice with "Y"-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey's multiple comparison post-test, Kruskal-Wallis test with Dunn's multiple comparison, χ2 test and Spearman correlation. High parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines. These experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.

Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

PubMed

Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

2016-06-01

Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The "continuum" of a unified theory of diseases.

PubMed

Vithoulkas, George; Carlino, Stefano

2010-02-01

This essay's theme was inspired by a question asked by a child: 'Why do I get ill?' The question is very interesting, but has no easy answer. This paper discusses a few possible answers to this difficult question. Through the life of a person, from birth to death, there is a "continuum" in the pathological conditions a person may experience. The body, as a whole, suffers deeply any time there is an acute or a chronic condition that is either maltreated or neglected. Chronic and acute diseases in the medical history of a person constitute a rigidly related chain of immune responses in the form of a real "continuum" that at every point in time indicates the end result of this continuum. The idea promoted here is that suppression of diseases, through excess of chemical drugs or other means, many times overwhelms the body's natural defenses and forces the immune system to compromise and start a deeper line of defense, which then constitute the beginning of a new chronic condition. Thus, the original inflammation of an acute condition may continue as a sub-acute inflammatory process on a deeper level. Acute inflammatory conditions must therefore be treated very carefully from their beginnings in childhood in order not to force the immune system to compromise. It is also suggested here that all chronic degenerative conditions have a sub-acute inflammatory character, and that "inflammation" constitutes the main common parameter of all diseases.

Influence of Acute and Chronic Exercise on Glucose Uptake

PubMed Central

Röhling, Martin; Herder, Christian; Stemper, Theodor; Müssig, Karsten

2016-01-01

Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role. PMID:27069930

Traumeel – an emerging option to nonsteroidal anti-inflammatory drugs in the management of acute musculoskeletal injuries

PubMed Central

Schneider, Christian

2011-01-01

Musculoskeletal injuries are on the rise. First-line management of such injuries usually employs the RICE (rest, ice, compression, and elevation) approach to limit excessive inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are also commonly used to limit inflammation and to control pain. Traumeel®, a preparation with bioregulatory effects is also used to treat the symptoms associated with acute musculoskeletal injuries, including pain and swelling. Traumeel is a fixed combination of biological and mineral extracts, which aims to apply stimuli to multiple targets to restore normal functioning of regulatory mechanisms. This paper presents the accumulating evidence of Traumeel’s action on the inflammatory process, and of its efficacy and tolerability in randomized trials, as well as observational and surveillance studies for the treatment of musculoskeletal injuries. Traumeel has shown comparable effectiveness to NSAIDs in terms of reducing symptoms of inflammation, accelerating recovery, and improving mobility, with a favorable safety profile. While continued research and development is ongoing to broaden the clinical evidence of Traumeel in acute musculoskeletal injury and to further establish its benefits, current information suggests that Traumeel may be considered as an anti-inflammatory agent that is at least as effective and appears to be better tolerated than NSAIDs. PMID:21556350

Dynamic Modulation of Microglia/Macrophage Polarization by miR-124 after Focal Cerebral Ischemia.

PubMed

Hamzei Taj, Somayyeh; Kho, Widuri; Aswendt, Markus; Collmann, Franziska M; Green, Claudia; Adamczak, Joanna; Tennstaedt, Annette; Hoehn, Mathias

2016-12-01

Mononuclear phagocytes respond to ischemic stroke dynamically, undergoing an early anti-inflammatory and protective phenotype followed by the pro-inflammatory and detrimental type. These dual roles of microglia/macrophages suggest the need of subtle adjustment of their polarization state instead of broad suppression. The most abundant brain-specific miRNA, miR-124, promotes neuronal differentiation but can also modulate microglia activation and keeps them in a quiescent state. We addressed whether the intracerebral injection of miR-124 in a mouse model of ischemic stroke before or after the peak phase of the pro-inflammatory polarization modifies the pro-/anti- inflammatory balance. In the sub-acute phase, 48 h after stroke, liposomated miR-124 shifted the predominantly pro-inflammatory polarized microglia/macrophages toward the anti-inflammatory phenotype. The altered immune response improved neurological deficit at day 6 after stroke. When miR-124 was injected 10 days after stroke, the pro-/anti- inflammatory ratio was still significantly reduced although to a lower degree and had no effect on recovery at day 14. This study indicates that miR-124 administration before the peak of the pro-inflammatory process of stroke is most effective in support of increasing the rehabilitation opportunity in the sub-acute phases of stroke. Our findings highlight the important role of immune cells after stroke and the therapeutic relevance of their polarization balance.

[The way of self-defence of the organism: inflammation].

PubMed

Jakab, Lajos

2013-08-11

The acute and chronic constitutional reactions of the organism elicited by sterile causes and pathogenic structures threatening the soundness of the organism are surveyed by the author. It is emphasized that depending on causes which can be very different, there are various syndromes occurring in the clinical practice. On the basis of multitudiness of pathogenic factors and individual differences, the infammatory reactions are clinically, pathologically and pathobiochemically can be hugely variable. The acute inflammatory response may be sterile. It is often difficult to recognize in these processes whether the inflammation is harmful or beneficial for the organism as a whole. It is possible that the inflammatory response itself is the defending resource of the individual. The non-sterile acute inflammation is evoked by pathogenic microorganisms. The variety of clinical syndromes are explained by the high diversity of pathogenic microbes, the individualities of the defending organisms, and the natural and adaptive immunity of the organism which may be intact or possibly defective. In the latter case the inflammation itself is the disease, as a consequence of a pathological process conducted by the cortico-hypothalamo-adernal axis. The acute inflammation is a defending, preventing and repairing process, constituting an important part of the natural innate immune response. It is inseparable from the natural innate immune response, which is in close cooperation with the adaptive, specific immune response with mutual effects on each of the other. The conductor and the response reactions of the two immune responses are also the same. There are alterations in serum proteins/glycoproteins synthesized mostly by the hepatocytes. Because the concentration of almost all proteins/glycoproteins may change, the use of the discriminative term "acute phase reactant" is hardly relevant. For example, the HDL molecule is a negative "acute phase reactant". On the gound of clinical, pathological and biochemical caracteristics, the chronic sterile inflammation is a very different entity. It has been established that atherosclerosis is one of the ab origine chronic inflammatory syndrome. It is a long-lasting pathological entity progressing, rather than resolving with different celerity, namely a unique vasculitis syndrome. We are speaking about risk factors instead of causes, which constitute larger or smaller groups to elicite the preventing reaction of the host. The propagations and final outcomes are quite different from that of the acute process. The disadvantages or benefits for the organism are scarcely predictable, albeit the chronic process may have roles in its prolonged nature.

Acute coronary disease Athero-Inflammation: Therapeutic approach

PubMed Central

Altman, Raul

2003-01-01

Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events. Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease. PMID:12904261

Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

PubMed

Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

2002-03-01

Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist

PubMed Central

Nakamura, Taichi; Ito, Tetsuhide; Uchida, Masahiko; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Jensen, Robert T.; Takayanagi, Ryoichi

2013-01-01

Background and Aims There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term GLP-1 analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells is well studied, however there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can play an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute/chronic pancreatitis, and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. Methods GLP-1R expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP1R expression and effects of GLP-1 analog on activated PSCs was examined with realtime PCR, MTS assays and Western Blotting. Results In normal pancreas, pancreatic β cells expressed GLP-1R, with only low expression in acinar cells, whereas in acute or chronic pancreatitis, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the ERK pathway mediated the PSCs proliferation. Conclusions GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in acute/chronic pancreatitis. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas. PMID:24217090

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

PubMed Central

2012-01-01

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers. PMID:22747645

Pereskia aculeata Miller leaves present in vivo topical anti-inflammatory activity in models of acute and chronic dermatitis.

PubMed

Pinto, Nícolas de Castro Campos; Machado, Danielle Cunha; da Silva, Josiane Mello; Conegundes, Jéssica Leiras Mota; Gualberto, Ana Cristina Moura; Gameiro, Jacy; Moreira Chedier, Luciana; Castañon, Maria Christina Marques Nogueira; Scio, Elita

2015-09-15

The leaves of Pereskia aculeata Miller (Cactaceae), known as Barbados gooseberry, are used in Brazilian traditional medicine as emollients and to treat skin wounds and inflammation. This study investigated the topical anti-inflammatory activity of the hexane fraction (HF) obtained from the methanol extract of the leaves of this species in models of acute and chronic ear dermatitis in mice. Mice ear edema was induced by topical application of croton oil, arachidonic acid, capsaicin, ethyl-phenylpropiolate and phenol; and by subcutaneous injection of histamine. Ear biopsies were obtained to determine the levels of IL-1β, IL-6 and TNF-α cytokines by ELISA assay. Histopathological analysis was also performed to evaluate the HF activity in croton oil multiple application test. In addition, acute dermal irritation/corrosion test in rats was accomplished. HF chemical characterization was performed by GC-MS analysis. HF intensively reduced the inflammatory process induced by all irritant agents used, except for arachidonic acid. This activity is related, at least in part, to the reduction of IL-6 and TNF-α cytokines levels. Moreover, when the glucocorticoid receptor antagonist mifepristone was used, HF failed to respond to the croton oil application.The results strongly suggested a glucocorticoid-like effect, which was reinforced by the presence of considerable amounts of sterol compounds identified in HF. The acute dermal irritaton/corrosion test showed no signs of toxicity. This study showed that the acute and chronic anti-inflammatory activity of P. aculeata leaves is very promising, and corroborates to better understand their ethnopharmacological applications. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Low power infrared laser modifies the morphology of lung affected with acute injury induced by sepsis

NASA Astrophysics Data System (ADS)

Sergio, L. P. S.; Trajano, L. A. S. N.; Thomé, A. M. C.; Mencalha, A. L.; Paoli, F.; Fonseca, A. S.

2018-06-01

Acute lung injury (ALI) is a potentially fatal disease characterized by uncontrolled hyperinflammatory responses in the lungs as a consequence of sepsis. ALI is divided into two sequential and time-dependent phases, exudative and fibroproliferative phases, with increased permeability of the alveolar barrier, causing edema and inflammation. However, there are no specific treatments for ALI. Low-power lasers have been successfully used in the resolution of acute inflammatory processes. The aim of this study was to evaluate the effects of low-power infrared laser exposure on alveolus and interalveolar septa of Wistar rats affected by ALI-induced by sepsis. Laser fluences, power, and the emission mode were those used in clinical protocols for the treatment of acute inflammation. Adult male Wistar rats were randomized into six groups: control, 10 J cm‑2, 20 J cm‑2, ALI, ALI  +  10 J cm‑2, and ALI  +  20 J cm‑2. ALI was induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS). Lungs were removed and processed for hematoxylin–eosin staining. Morphological alterations induced by LPS in lung tissue were quantified by morphometry with a 32-point cyclic arcs test system in Stepanizer. Data showed that exposure to low-power infrared laser in both fluences reduced the thickening of interalveolar septa in lungs affected by ALI, increasing the alveolar space; however, inflammatory infiltrate was still observed. Our research showed that exposure to low-power infrared laser improves the lung parenchyma in Wistar rats affected by ALI, which could be an alternative approach for treatment of inflammatory lung injuries.

Regulation of alveolar macrophage death in acute lung inflammation.

PubMed

Fan, Erica K Y; Fan, Jie

2018-03-27

Acute lung injury (ALI) and its severe form, known as acute respiratory distress syndrome (ARDS), are caused by direct pulmonary insults and indirect systemic inflammatory responses that result from conditions such as sepsis, trauma, and major surgery. The reciprocal influences between pulmonary and systemic inflammation augments the inflammatory process in the lung and promotes the development of ALI. Emerging evidence has revealed that alveolar macrophage (AM) death plays important roles in the progression of lung inflammation through its influence on other immune cell populations in the lung. Cell death and tissue inflammation form a positive feedback cycle, ultimately leading to exaggerated inflammation and development of disease. Pharmacological manipulation of AM death signals may serve as a logical therapeutic strategy for ALI/ARDS. This review will focus on recent advances in the regulation and underlying mechanisms of AM death as well as the influence of AM death on the development of ALI.

Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction

PubMed Central

Alestalo, Kirsi; Miettinen, Johanna A.; Vuolteenaho, Olli; Huikuri, Heikki; Lehenkari, Petri

2015-01-01

Background Acute myocardial infarction (AMI) launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC) transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI). Methods Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection. Results Twenty-six patients (control group, n = 12; BMMNC group, n = 14) from the previously reported FINCELL study (n = 80) were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall’s tau, control 0.6; BMMNC 0.7). At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall’s tau, control 0.3; BMMNC 0.7). Conclusions BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI. PMID:26690350

Acute phase protein haptoglobin as inflammatory marker in serum and synovial fluid in an equine model of arthritis.

PubMed

Barrachina, Laura; Remacha, Ana Rosa; Soler, Lourdes; García, Natalia; Romero, Antonio; Vázquez, Francisco José; Vitoria, Arantza; Álava, María Ángeles; Lamprave, Fermín; Rodellar, Clementina

2016-12-01

Acute phase proteins are useful inflammatory markers in horses. Haptoglobin (Hp) serum level is increased in horses undergoing different inflammatory processes, including arthritis. However, Hp concentration has not been assessed in inflammatory synovial fluid (SF). The aim of the present study was to investigate the Hp response in serum and SF in horses undergoing experimentally induced arthritis. For this purpose, serum and SF samples were collected from 12 animals before amphotericin B-induced arthritis was created (T0, healthy) and 15days after the lesion induction (T1, joint inflammation) and Hp was determined by single radial immunodiffusion. The Hp increase between T0 and T1 was significant in both serum and SF, and serum Hp concentration at T0 was significantly higher than in SF, but significant differences were not found at T1, indicating a higher Hp increase in SF. A significant positive correlation for Hp concentration between serum and SF samples was found. These results highlight the potential usefulness of Hp as inflammatory marker in horses, showing for the first time the increase of Hp in SF from joint inflammation in the horse. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis.

PubMed

Lupia, Enrico; Pigozzi, Luca; Goffi, Alberto; Hirsch, Emilio; Montrucchio, Giuseppe

2014-11-07

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis.

Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis

PubMed Central

Lupia, Enrico; Pigozzi, Luca; Goffi, Alberto; Hirsch, Emilio; Montrucchio, Giuseppe

2014-01-01

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis. PMID:25386068

Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis

PubMed Central

Bleau, Christian; Filliol, Aveline; Samson, Michel

2016-01-01

ABSTRACT Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis. PMID:27489277

Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis.

PubMed

Bleau, Christian; Filliol, Aveline; Samson, Michel; Lamontagne, Lucie

2016-10-15

Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice.

PubMed

Fiechter, Danielle; Kats, Suzanne; Brands, Ruud; van Middelaar, Ben; Pasterkamp, Gerard; de Kleijn, Dominique; Seinen, Willem

2011-10-01

There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction.

Management of Acute Exacerbation of Asthma and Chronic Obstructive Pulmonary Disease in the Emergency Department.

PubMed

Suau, Salvador J; DeBlieux, Peter M C

2016-02-01

Acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations are the most common respiratory diseases requiring emergent medical evaluation and treatment. Asthma and COPD are chronic, debilitating disease processes that have been differentiated traditionally by the presence or absence of reversible airflow obstruction. Asthma and COPD exacerbations impose an enormous economic burden on the US health care budget. In daily clinical practice, it is difficult to differentiate these 2 obstructive processes based on their symptoms, and on their nearly identical acute treatment strategies; major differences are important when discussing anatomic sites involved, long-term prognosis, and the nature of inflammatory markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Salivary Markers of Inflammation in Response to Acute Stress

PubMed Central

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

2014-01-01

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

Cot/tpl2 (MAP3K8) mediates myeloperoxidase activity and hypernociception following peripheral inflammation.

PubMed

Soria-Castro, Irene; Krzyzanowska, Agnieszka; Pelaéz, Marta López; Regadera, Javier; Ferrer, Gema; Montoliu, Lluis; Rodríguez-Ramos, Rosario; Fernández, Margarita; Alemany, Susana

2010-10-29

Cot/tpl2 (also known as MAP3K8) has emerged as a new and potentially interesting therapeutic anti-inflammatory target. Here, we report the first study of Cot/tpl2 involvement in acute peripheral inflammation in vivo. Six hours after an intraplantar injection of zymosan, Cot/tpl2(-/-) mice showed a 47% reduction in myeloperoxidase activity, concomitant with a 46% lower neutrophil recruitment and a 40% decreased luminol-mediated bioluminescence imaging in vivo. Accordingly, Cot/tpl2 deficiency provoked a 25-30% reduction in luminol-mediated bioluminescence and neutrophil recruitment together with a 65% lower macrophage recruitment 4 h following zymosan-induced peritonitis. Significantly impaired levels of G-CSF and GM-CSF and of other cytokines such as TNFα, IL-1β, and IL-6, as well as some chemokines such as MCP-1, MIP-1β, and keratinocyte-derived chemokine, were detected during the acute zymosan-induced intraplantar inflammatory response in Cot/tpl2(-/-) mice. Moreover, Cot/tpl2 deficiency dramatically decreased the production of the hypernociceptive ligand NGF at the inflammatory site during the course of inflammation. Most importantly, Cot/tpl2 deficiency significantly reduced zymosan-induced inflammatory hypernociception in mice, with a most pronounced effect of a 50% decrease compared with wild type (WT) at 24 h following intraplantar injection of zymosan. At this time, Cot/tpl2(-/-) mice showed significantly reduced NGF, TNFα, and prostaglandin E(2) levels compared with WT littermates. In conclusion, our study demonstrates an important role of Cot/tpl2 in the NGF, G-CSF, and GM-CSF production and myeloperoxidase activity in the acute inflammatory response process and its implication in inflammatory hypernociception.

Hypothalamic inflammation in obesity and metabolic disease.

PubMed

Jais, Alexander; Brüning, Jens C

2017-01-03

Over the last years, hypothalamic inflammation has been linked to the development and progression of obesity and its sequelae. There is accumulating evidence that this inflammation not only impairs energy balance but also contributes to obesity-associated insulin resistance. Elevated activation of key inflammatory mediators such as JNK and IκB kinase (IKK) occurs rapidly upon consumption of a high-fat diet, even prior to significant weight gain. This activation of hypothalamic inflammatory pathways results in the uncoupling of caloric intake and energy expenditure, fostering overeating and further weight gain. In addition, these inflammatory processes contribute to obesity-associated insulin resistance and deterioration of glucose metabolism via altered neurocircuit functions. An understanding of the contributions of different neuronal and non-neuronal cell types to hypothalamic inflammatory processes, and delineation of the differences and similarities between acute and chronic activation of these inflammatory pathways, will be critical for the development of novel therapeutic strategies for the treatment of obesity and metabolic syndrome.

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

PubMed

Ribeiro, Alison; Ferraz-de-Paula, Viviane; Pinheiro, Milena L; Vitoretti, Luana B; Mariano-Souza, Domenica P; Quinteiro-Filho, Wanderley M; Akamine, Adriana T; Almeida, Vinícius I; Quevedo, João; Dal-Pizzol, Felipe; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Palermo-Neto, João

2012-03-05

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor. Copyright © 2012 Elsevier B.V. All rights reserved.

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…

Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice

PubMed Central

Fiechter, Danielle; Kats, Suzanne; Brands, Ruud; van Middelaar, Ben; Pasterkamp, Gerard; de Kleijn, Dominique; Seinen, Willem

2011-01-01

Background There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Methods Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Results Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. Conclusion In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction. PMID:28357012

Comorbidity between depression and inflammatory bowel disease explained by immune-inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut-brain pathways.

PubMed

Martin-Subero, Marta; Anderson, George; Kanchanatawan, Buranee; Berk, Michael; Maes, Michael

2016-04-01

The nature of depression has recently been reconceptualized, being conceived as the clinical expression of activated immune-inflammatory, oxidative, and nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT), autoimmune, and gut-brain pathways. IO&NS pathways are similarly integral to the pathogenesis of inflammatory bowel disease (IBD). The increased depression prevalence in IBD associates with a lower quality of life and increased morbidity in IBD, highlighting the role of depression in modulating the pathophysiology of IBD.This review covers data within such a wider conceptualization that better explains the heightened co-occurrence of IBD and depression. Common IO&NS underpinning between both disorders is evidenced by increased pro-inflammatory cytokine levels, eg, interleukin-1 (IL-1) and tumor necrosis factor-α, IL-6 trans-signalling; Th-1- and Th-17-like responses; neopterin and soluble IL-2 receptor levels; positive acute phase reactants (haptoglobin and C-reactive protein); lowered levels of negative acute phase reactants (albumin, transferrin, zinc) and anti-inflammatory cytokines (IL-10 and transforming growth factor-β); increased O&NS with damage to lipids, proteinsm and DNA; increased production of nitric oxide (NO) and inducible NO synthase; lowered plasma tryptophan but increased TRYCAT levels; autoimmune responses; and increased bacterial translocation. As such, heightened IO&NS processes in depression overlap with the biological underpinnings of IBD, potentially explaining their increased co-occurrence. This supports the perspective that there is a spectrum of IO&NS disorders that includes depression, both as an emergent comorbidity and as a contributor to IO&NS processes. Such a frame of reference has treatment implications for IBD when "comorbid" with depression.

Immune dysfunction in cirrhosis.

PubMed

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-03-14

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality.

Immune dysfunction in cirrhosis

PubMed Central

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-01-01

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

The Effect of Intra-Dialytic Exercise on Inflammation and Blood Endotoxin Levels.

PubMed

Wong, Jonathan; Davis, Philip; Patidar, Ashish; Zhang, Yonglong; Vilar, Enric; Finkelman, Malcolm; Farrington, Ken

2017-01-01

In healthy individuals, an acute inflammatory response occurs after intense exercise due to gut ischaemia and intestinal bacterial endotoxin translocation into the bloodstream. This process maybe exacerbated in patients who exercise during dialysis due to large volume shifts experienced by many during haemodialysis (HD). The acute effect of intra-dialytic exercise on blood endotoxins and inflammation is not known. The effect of intra-dialytic exercise on blood endotoxin and inflammation was investigated in 10 patients and compared with resting haemodialysis. Blood was measured for endotoxin and inflammatory biomarkers before and after dialysis. With the exception of one sample, all samples tested negative for endotoxin. Intra-dialytic exercise attenuated the rise of interleukin-6, tumour necrosis factor-α and high-sensitivity C-reactive protein after the HD procedure. Intra-dialytic exercise was not associated with an observable rise in blood endotoxin, although it may ameliorate the inflammatory effects of the HD procedure. Larger studies are needed to confirm this finding. © 2017 S. Karger AG, Basel.

Evaluation of the analgesic effect of low-power optical radiation in acute inflammatory process

NASA Astrophysics Data System (ADS)

Ferreira, Denise M.; Zangaro, Renato A.; Cury, Yara; Frigo, Lucio; Barbosa, Daniella G.; da Silva Melo, Milene; Munin, Egberto

2004-07-01

Many research works have explored the use of the low power laser as a tool for the control of inflammatory processes. The anti-inflammatory effect of low power optical radiation and its ability to induce analgesia has been reported for different experimental conditions. Many published works are very qualitative in nature. In this work the action of low power laser radiation on acute inflammatory process is evaluated. The time evolution of rat paw edema and pain induced by carrageenan was experimentally monitored. A 632.8 nm He-Ne laser was used for the treatment. The laser treatment, at a dosage of 2,5 J/cm2, was applied at the first, second and third hour after the induction of the inflammation. A hydroplethysmometer was used for the evaluation of the inflammation. The measurement of pain sensitivity was performed according to the method described by Randall and Selito, (1957). The laser treatment was capable of inhibiting the carrageenan-induced hyperalgesia by 49% (p<0,001) at the second hour after the induction, as compared to the non-treated group. At the fourth hour (peak of the carrageenan action on hyperalgesia) and at the sixth hour, the achieved inhibition was 49% (p<0,001) and 61% (p<0,001), respectively. In the treated groups, the edema evolution was inhibited by 38% (p<0,01), at the second hour after induction, as compared to the non-treated groups. At the fourth hour (peak of the carrageenan action on leakage) and at sixth hour the achieved inhibition was 35% (p<0,01) and 30% (p<0,05) respectively.

[Angle-closure glaucoma secondary to nonspecific orbital inflammatory: case report].

PubMed

Násser, Luciano Sólia; Liendo da Costa, Vera Lucia; Taniguchi, Marcel Papa; Bolanho, Anamaria; Petrilli, Ana Maria Noriega

2007-01-01

The nonspecific orbital inflammatory presents several clinical forms. When it evolves the posterior segment of the eye, usually by contiguity, it can lead to serious damage to vision functions. Posterior scleritis causes permanent damage to the vision and rarely progresses to acute glaucoma. E.N., a 24-year-old black man, complained of pain in the left eye (OS) for ten days, with low visual acuity, malaise, nauseas and vomiting. On ophthalmologic examination, he presented proptosis, restricted eye movements and edema on the upper left eyelid. Best-corrected visual acuity was 20/20 in OD and counting fingers at 1.5m in OS. The intraocular pressure was 14 mmHg in OD and 34 mmHg in OS. The biomicroscopy presented in OS conjunctival hyperemia cornea with keratic precipitates, shallow anterior chamber with cells and flare 2+. Gonioscopy in OS showed angle-closure of 360 masculine. The ophthalmoscopic examination revealed increased vascular tortuosity and posterior pole edema. Treatment for acute glaucoma was initiated and complementary tests were ordered. Ocular ultrasonography and orbit computerized tomography showed a diffuse thickening of the ocular wall and extrinsic muscles. Other tests were normal. The presumptive diagnosis was acute nonspecific orbital inflammation affecting the ocular bulb posterior segment together with acute glaucoma. He initiated on prednisone 60 mg/day PO. After two weeks of systemic corticotherapy, the patient was asymptomatic, with evident regression of proptosis and scleritis and normal intraocular pressure (11 mmHg in AU). Although not very frequent, acute glaucoma may be present in orbital inflammatory process and should be treated with systemic corticotherapy and topical medication.

Self-esteem levels and cardiovascular and inflammatory responses to acute stress.

PubMed

O'Donnell, Katie; Brydon, Lena; Wright, Caroline E; Steptoe, Andrew

2008-11-01

Acute mental stress tests have helped to clarify the pathways through which psychosocial factors are linked to disease risk. This methodology is now being used to investigate potentially protective psychosocial factors. We investigated whether global self-esteem might buffer cardiovascular and inflammatory responses to acute stress. One hundred and one students completed the Rosenberg Self-Esteem Scale. Heart rate and heart rate variability (HRV) were recorded for 5 min periods at baseline, during two mental stress tasks, (a speech and a color-word task) and 10, 25 and 40 min into a recovery period. Plasma levels of tumor-necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra) were assessed at baseline, immediately post-stress and after 45 min recovery. Repeated measures analysis of variance demonstrated that heart rate levels were lower across all time points in those with high self-esteem, although heart rate reactivity to stress was not related to self-esteem. There were no differences in baseline HRV, TNF-alpha, IL-6 or IL-1Ra. Multiple linear regressions revealed that greater self-esteem was associated with a smaller reduction in heart rate variability during the speech task, but not the color-word task. Greater self-esteem was associated with smaller TNF-alpha and IL-1Ra responses immediately following acute stress and smaller IL-1Ra responses at 45 min post-stress. In conclusion, global self-esteem is associated with lower heart rate and attenuated HRV and inflammatory responses to acute stress. These responses could be processes through which self-esteem protects against the development of disease.

Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

PubMed Central

Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

2012-01-01

Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

Cytokine mediated tissue fibrosis☆

PubMed Central

Borthwick, Lee A.; Wynn, Thomas A.; Fisher, Andrew J.

2013-01-01

Acute inflammation is a recognised part of normal wound healing. However, when inflammation fails to resolve and a chronic inflammatory response is established this process can become dysregulated resulting in pathological wound repair, accumulation of permanent fibrotic scar tissue at the site of injury and the failure to return the tissue to normal function. Fibrosis can affect any organ including the lung, skin, heart, kidney and liver and it is estimated that 45% of deaths in the western world can now be attributed to diseases where fibrosis plays a major aetiological role. In this review we examine the evidence that cytokines play a vital role in the acute and chronic inflammatory responses that drive fibrosis in injured tissues. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. PMID:23046809

The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs.

PubMed

Franchin, Marcelo; Freires, Irlan Almeida; Lazarini, Josy Goldoni; Nani, Bruno Dias; da Cunha, Marcos Guilherme; Colón, David Fernando; de Alencar, Severino Matias; Rosalen, Pedro Luiz

2018-06-10

Anti-Inflammatory drugs have been routinely used in the management of acute and chronic inflammatory conditions. Nevertheless, their undesirable side and adverse effects have encouraged the development of more selective, tolerable and efficacious drugs able to modulate the inflammatory process through distinct mechanisms than those of drugs currently available in the market, for instance, inhibition of leukocyte recruitment (chemotaxis, rolling, adhesion and transmigration). Natural products, including Brazilian propolis, have been considered a rich source of anti-inflammatory molecules due to a very complex phytochemical diversity. Brazil has at least thirteen distinct types of propolis and many bioactive compounds have been isolated therefrom, such as apigenin, artepillin C, vestitol, neovestitol, among others. These molecules were proven to play a significant immunomodulatory role through (i) inhibition of inflammatory cytokines (e.g. TNF-α) and chemokines (CXCL1/KC and CXCL2/MIP2); (ii) inhibition of IκBα, ERK1/2, JNK and p38MAPK phosphorylation; (iii) inhibition of NF-κB activation; and (iv) inhibition of neutrophil adhesion and transmigration (ICAM-1, VCAM-1 and E-selectin expression). In this review, we shed light on the new advances in the research of compounds isolated from Brazilian propolis from Apis mellifera bees as potentially novel anti-inflammatory drugs. The compilation of data and insights presented herein may open further avenues for the pharmacological management of oral and systemic inflammatory conditions. Further research should focus on clinical and acute/chronic toxicological validation of the most promising compounds described in this review. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

An old disease with new insights: Update on diagnosis and treatment of gout

PubMed Central

Bitik, Berivan; Öztürk, M. Akif

2014-01-01

Gout is an acute and chronic inflammatory disorder associated with high morbidity and impaired quality of life. There has been a substantial increase in the prevalence and incidence of gout in recent years. Novel diagnostic and therapeutic options have provided new insights into the pathogenesis and management of hyperuricemia and gout in the last decade. This clinical review aims to summarize the diagnostic process and management of acute and chronic gout. PMID:27708879

Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure.

PubMed

Woolbright, Benjamin L; Jaeschke, Hartmut

2017-04-01

Drug-induced acute liver failure carries a high morbidity and mortality rate. Acetaminophen overdose is the number one cause of acute liver failure and remains a major problem in Western medicine. Administration of N-acetyl cysteine is an effective antidote when given before the initial rise in toxicity; however, many patients present to the hospital after this stage occurs. As such, treatments which can alleviate late-stage acetaminophen-induced acute liver failure are imperative. While the initial mechanisms of toxicity are well described, a debate has recently occurred in the literature over whether there is a second phase of injury, mediated by inflammatory processes. Critical to this potential inflammatory process is the activation of caspase-1 and interleukin-1β by a molecular complex known as the inflammasome. Several different stimuli for the formation of multiple different inflammasome complexes have been identified. Formation of the NACHT, leucine-rich repeat (LRR) and pyrin (PYD) domains-containing protein 3 (Nalp3) inflammasome in particular, has directly been attributed to late-stage acetaminophen toxicity. In this review, we will discuss the mechanisms of acetaminophen-induced liver injury in mice and man with a particular focus on the role of inflammation and the inflammasome. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Stepwise approach to myopathy in systemic disease.

PubMed

Chawla, Jasvinder

2011-01-01

Muscle diseases can constitute a large variety of both acquired and hereditary disorders. Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness myopathy, metabolic, and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesions; the incidence appears to be specifically increased only in patients with dermatomyositis. In dealing with myopathies associated with systemic illnesses, the focus will be on the acquired causes. Management is beyond the scope of this chapter. Prognosis is based upon the underlying cause and, most of the time, carries a good prognosis. In order to approach a patient with suspected myopathy from systemic disease, a stepwise approach is utilized.

Resolution of inflammation: state of the art, definitions and terms

PubMed Central

Serhan, Charles N.; Brain, Sue D.; Buckley, Christopher D.; Gilroy, Derek W.; Haslett, Christopher; O’Neill, Luke A. J.; Perretti, Mauro; Rossi, Adriano G.; Wallace, John L.

2011-01-01

A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution. PMID:17267386

Acute and chronic stress and the inflammatory response in hyperprolactinemic rats.

PubMed

Ochoa-Amaya, J E; Malucelli, B E; Cruz-Casallas, P E; Nasello, A G; Felicio, L F; Carvalho-Freitas, M I R

2010-01-01

Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period. Copyright 2010 S. Karger AG, Basel.

The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress.

PubMed

Ren, Jiayi; Liu, Chunpeng; Zhao, Dan; Fu, Jing

2018-05-15

The aim of this study was to investigate the role of heat shock protein 70 (Hsp70) in oxidative stress and inflammatory damage in the spleen of quails which were induced by cold stress. One hundred ninety-two 15-day-old male quails were randomly divided into 12 groups and kept at 12 ± 1 °C to examine acute and chronic cold stress. We first detected the changes in activities of antioxidant enzymes in the spleen tissue under acute and chronic cold stress. The activities of glutathione peroxidase (GSH-Px) fluctuated in acute cold stress groups, while they were significantly decreased (p < 0.05) after chronic cold stress. The activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) content were decreased significantly (p < 0.05) in both of the acute and chronic cold stress groups. Malondialdehyde (MDA) content was significantly increased (p < 0.05) under cold stress except the 0.5 h group of acute cold stress. Besides, histopathological analysis showed that quail's spleen tissue was inflammatory injured seriously in both the acute and chronic cold stress groups. Additionally, the inflammatory factors (cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), iNOS, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-a (TNF-α)) and Hsp70 mRNA levels were increased in both of the acute and chronic cold stress groups compared with the control groups. These results suggest that oxidative stress and inflammatory injury could be induced by cold stress in spleen tissues of quails. Furthermore, the increased expression of Hsp70 may play a role in protecting the spleen against oxidative stress and inflammatory damage caused by cold stress.

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

PubMed Central

Bonaventura, Aldo; Liberale, Luca; Vecchié, Alessandra; Casula, Matteo; Carbone, Federico; Dallegri, Franco; Montecucco, Fabrizio

2016-01-01

After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies. PMID:27898011

Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome.

PubMed

Ma, Cai-Yun; Liu, Jing-Hua; Liu, Jian-Xun; Shi, Da-Zhuo; Xu, Zhen-Ye; Wang, Shao-Ping; Jia, Min; Zhao, Fu-Hai; Jiang, Yue-Rong; Ma, Qin; Peng, Hong-Yu; Lu, Yuan; Zheng, Ze; Ren, Feng-Xue

2017-11-01

To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS). Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05). Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

PubMed

Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

2015-02-01

We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

Acute inflammatory edema of the uvula (uvulitis) as a cause of respiratory distress: a case report.

PubMed

Hawke, M; Kwok, P

1987-06-01

Acute inflammatory edema of the uvula (uvulitis) is a relatively rare cause of upper airway distress or obstruction. The authors present a case report of a 37-year-old man who developed an acute cellulitis and edema of the uvula with upper airway distress, which was managed by an emergency uvulectomy.

Autophagy and kidney inflammation

PubMed Central

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-01-01

ABSTRACT Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases. PMID:28441075

Autophagy and kidney inflammation.

PubMed

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-06-03

Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases.

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

Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise.

PubMed

Pillon Barcelos, Rômulo; Freire Royes, Luiz Fernando; Gonzalez-Gallego, Javier; Bresciani, Guilherme

2017-02-01

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.

Anti-inflammatory effect of combined tetramethylpyrazine, resveratrol and curcumin in vivo.

PubMed

Chen, Long; Liu, Tianjun; Wang, Qiangsong; Liu, Juan

2017-04-27

Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo. The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD 50 was measured based on the acute oral toxicity (AOT) standard method. The best formulation was the three components combined at the same mass proportion revealed by the Uniform Design methodology. This combination could significantly reduce the paw swelling in acute paw swelling mouse model, could reduce paw swelling and alleviate the damage in joint structural of ankle, cartilages and fibrous tissue in CIA rat model. The dose relationship was clear in both cases. Immunohistochemical staining of ankle tissue revealed that TRC combination was able to inhibit the expression of NF-κB p65 and TNF-α which were closely related to the inflammatory process. Analysis of serum mediators revealed TRC combination could inhibit the production of TNF-α, IL-1β, and IL-6 in the serum. Toxic study revealed this formulation was low toxic, LD 50 was larger than 5 g/kg, both the level of ALT and AST and histopathology in the liver and kidney exhibited no distinctions between the TRC combination and the blank group, no mortality occurred at the administered doses of 5 g/kg. The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells.

PubMed

Matsuzaki, Koichi

2012-01-01

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis.

Light-emitting diode therapy reduces persistent inflammatory pain: Role of interleukin 10 and antioxidant enzymes.

PubMed

Martins, D F; Turnes, B L; Cidral-Filho, F J; Bobinski, F; Rosas, R F; Danielski, L G; Petronilho, F; Santos, A R S

2016-06-02

During the last decades, the use of light-emitting diode therapy (LEDT) has increased significantly for the treatment of wound healing, analgesia and inflammatory processes. Nevertheless, scientific data on the mechanisms responsible for the therapeutic effect of LEDT are still insufficient. Thus, this study investigated the analgesic, anti-inflammatory and anti-oxidative effect of LEDT in the model of chronic inflammatory hyperalgesia. Mice injected with Complete Freund's Adjuvant (CFA) underwent behavioral, i.e. mechanical and hot hyperalgesia; determination of cytokine levels (tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-10), oxidative stress markers (protein carbonyls and thiobarbituric acid reactive species (TBARS)) and antioxidant enzymes (catalase (CAT) and superoxide dismutase (SOD)). Additionally, mice were pretreated with either naloxone or fucoidin and mechanical hyperalgesia was assessed. LEDT inhibited mechanical and thermal hyperalgesia induced by CFA injection. LEDT did not reduce paw edema, neither influenced the levels of TNF-α and IL1-β; although it increased the levels of IL-10. LEDT significantly prevented TBARS increase in both acute and chronic phases post-CFA injection; whereas protein carbonyl levels were reduced only in the acute phase. LEDT induced an increase in both SOD and CAT activity, with effects observable in the acute but not in the chronic. And finally, pre-administration of naloxone or fucoidin prevented LEDT analgesic effect. These data contribute to the understanding of the neurobiological mechanisms involved in the therapeutic effect of LEDT as well as provides additional support for its use in the treatment of painful conditions of inflammatory etiology. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Inflammation and Alzheimer’s disease

PubMed Central

Akiyama, Haruhiko; Barger, Steven; Barnum, Scott; Bradt, Bonnie; Bauer, Joachim; Cole, Greg M.; Cooper, Neil R.; Eikelenboom, Piet; Emmerling, Mark; Fiebich, Berndt L.; Finch, Caleb E.; Frautschy, Sally; Griffin, W.S.T.; Hampel, Harald; Hull, Michael; Landreth, Gary; Lue, Lih–Fen; Mrak, Robert; Mackenzie, Ian R.; McGeer, Patrick L.; O’Banion, M. Kerry; Pachter, Joel; Pasinetti, Guilio; Plata–Salaman, Carlos; Rogers, Joseph; Rydel, Russell; Shen, Yong; Streit, Wolfgang; Strohmeyer, Ronald; Tooyoma, Ikuo; Van Muiswinkel, Freek L.; Veerhuis, Robert; Walker, Douglas; Webster, Scott; Wegrzyniak, Beatrice; Wenk, Gary; Wyss–Coray, Tony

2013-01-01

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer’s disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid β peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder. PMID:10858586

Role of Antioxidants and Natural Products in Inflammation

PubMed Central

Fard, Masoumeh Tangestani; Tan, Woan Sean; Gothai, Sivapragasam; Kumar, S. Suresh

2016-01-01

Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases. PMID:27803762

Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

PubMed

Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

2016-02-01

Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis. © 2015 Wiley Periodicals, Inc.

Anti-inflammatory effect of α,β-amyrin, a triterpene from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice.

PubMed

Melo, Caroline M; Morais, Talita C; Tomé, Adriana R; Brito, Gerly Anne C; Chaves, Mariana H; Rao, Vietla S; Santos, Flávia A

2011-07-01

To evaluate the anti-inflammatory effect of α,β-amyrin, a pentacyclic triterpenoid from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice. Acute pancreatitis was induced in Swiss mice by five intraperitoneal injections of cerulein (50 μg/kg), at 1 h intervals. Mice received α,β-amyrin (10, 30 and 100 mg/kg), thalidomide (200 mg/kg), or vehicle (3% Tween 80) orally 1 h before and 12 h after the cerulein challenge. The severity of pancreatitis was evaluated 24 h after cerulein by assessing serum pro-inflammatory cytokines and amylase activity, pancreatic myeloperoxidase (MPO), and thiobarbituric acid-reactive substances (TBARS), as well as by histology. α,β-Amyrin and thalidomide significantly attenuated the cerulein-induced increase in tumor necrosis factor (TNF)-α, interleukin-6, lipase, amylase, MPO, and TBARS. Moreover, α,β-amyrin greatly suppressed the pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and expressions of TNFα and inducible nitric oxide synthase. α,β-Amyrin ameliorates cerulein-induced acute pancreatitis by acting as an anti-inflammatory and antioxidant agent.

Systemic inflammatory response following acute myocardial infarction

PubMed Central

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

2015-01-01

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

Prospects of apoptotic cell-based therapies for transplantation and inflammatory diseases.

PubMed

Saas, Philippe; Kaminski, Sandra; Perruche, Sylvain

2013-10-01

Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.

Heme oxygenase-1 mediates the protective effects of ischemic preconditioning on mitigating lung injury induced by lower limb ischemia-reperfusion in rats.

PubMed

Peng, Tsui-Chin; Jan, Woan-Ching; Tsai, Pei-Shan; Huang, Chun-Jen

2011-05-15

Lower limb ischemia-reperfusion (I/R) imposes oxidative stress, elicits inflammatory response, and subsequently induces acute lung injury. Ischemic preconditioning (IP), a process of transient I/R, mitigates the acute lung injury induced by I/R. We sought to elucidate whether the protective effects of IP involve heme oxygenase-1 (HO-1). Adult male rats were randomized to receive I/R, I/R plus IP, I/R plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by reperfusion for 3 h. To achieve IP, three cycles of bilateral lower limb I/R (i.e., ischemia for 10 min followed by reperfusion for 10 min) were performed. IP was performed immediately before I/R. After sacrifice, degree of lung injury was determined. Histologic findings, together with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that I/R induced acute lung injury. I/R also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E(2) concentrations), imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations), and up-regulated HO-1 expression in lung tissues. IP significantly enhanced HO-1 up-regulation and, in turn, mitigated oxidative stress, inflammatory response, and acute lung injury induced by I/R. In addition, the protective effects of IP were counteracted by SnPP. The protective effects of IP on mitigating acute lung injury induced by lower limb I/R are mediated by HO-1. Copyright © 2011 Elsevier Inc. All rights reserved.

The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.

PubMed

Grabiec, Aleksander M; Hussell, Tracy

2016-07-01

Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections.

Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

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

Marín-Prida, Javier; Pavón-Fuentes, Nancy; Llópiz-Arzuaga, Alexey

2013-10-01

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD)more » were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.« less

Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats.

PubMed

Marín-Prida, Javier; Pavón-Fuentes, Nancy; Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R; Delgado-Roche, Liván; Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto; Pardo-Andreu, Gilberto L; Polentarutti, Nadia; Riva, Federica; Pentón-Arias, Eduardo; Pentón-Rol, Giselle

2013-10-01

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of acute naproxen administration on memory in young adults: A randomized, double-blind, placebo-controlled study.

PubMed

Wilson, Jack H; Criss, Amy H; Spangler, Sean A; Walukevich, Katherine; Hewett, Sandra

2017-10-01

Nonsteroidal anti-inflammatory drugs work by non-selectively inhibiting cyclooxygenase enzymes. Evidence indicates that metabolites of the cyclooxygenase pathway play a critical role in the process of learning and memory. We evaluated whether acute naproxen treatment impairs short-term working memory, episodic memory, or semantic memory in a young, healthy adult population. Participants received a single dose of placebo or naproxen (750 mg) in random order separated by 7-10 days. Two hours following administration, participants completed five memory tasks. The administration of acute high-dose naproxen had no effect on memory in healthy young adults.

Fingerprint of Lung Fluid Ultrafine Particles, a Novel Marker of Acute Lung Inflammation.

PubMed

Bar-Shai, Amir; Alcalay, Yifat; Sagiv, Adi; Rotem, Michal; Feigelson, Sara W; Alon, Ronen; Fireman, Elizabeth

2015-01-01

Acute lung inflammation can be monitored by various biochemical readouts of bronchoalveolar lavage fluid (BALF). To analyze the BALF content of ultrafine particles (UFP; <100 nm) as an inflammatory biomarker in early diagnosis of acute and chronic lung diseases. Mice were exposed to different stress conditions and inflammatory insults (acute lipopolysaccharide inhalation, tobacco smoke and lethal dose of total body irradiation, i.e. 950 rad). After centrifugation, the cellular pellet was assessed while cytokines and ultrafine particles were measured in the soluble fraction of the BALF. A characteristic UFP distribution with a D50 (i.e. the dimension of the 50th UFP percentile) was shared by all tested mouse strains in the BALF of resting lungs. All tested inflammatory insults similarly shifted this size distribution, resulting in a unique UFP fingerprint with an averaged D50 of 58.6 nm, compared with the mean UFP D50 of 23.7 nm for resting BALF (p < 0.0001). This UFP profile was highly reproducible and independent of the intensity or duration of the inflammatory trigger. It returned to baseline after resolution of the inflammation. Neither total body irradiation nor induction of acute cough induced this fingerprint. The UFP fingerprint in the BALF of resting and inflamed lungs can serve as a binary biomarker of healthy and acutely inflamed lungs. This marker can be used as a novel readout for the onset of inflammatory lung diseases and for complete lung recovery from different insults.

Granulomatous lobular mastitis.

PubMed

Galea, M H; Robertson, J F; Ellis, I O; Elston, C W; Blamey, R W

1989-07-01

The clinical and histological features of six cases of granulomatous lobular mastitis are presented. All six patients were parous. 1-6 years after their last pregnancy with a mean age of 34 years; all had unilateral disease and presented with an extra-areolar breast lump. Histologically, all demonstrated a non-caseating granulomatous inflammatory condition centered on breast lobules; in four women there was an acute inflammatory process with micro-abscess formation. Five of the six cases had persistent or recurrent disease despite wide local excision: surgery might not be the best treatment for recurrent disease.

Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

PubMed Central

Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

2015-01-01

Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.

PubMed

Quek, Amy May Lin; Soon, Derek; Chan, Yee Cheun; Thamboo, Thomas Paulraj; Yuki, Nobuhiro

2014-06-15

Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes. Copyright © 2014 Elsevier B.V. All rights reserved.

Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

PubMed

Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

2015-07-01

Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immune-modulating therapy in acute pancreatitis: Fact or fiction

PubMed Central

Akinosoglou, Karolina; Gogos, Charalambos

2014-01-01

Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future. PMID:25386069

Changes in serum interleukin-33 levels in patients with acute cerebral infarction.

PubMed

Liu, Jingyao; Xing, Yingqi; Gao, Ying; Zhou, Chunkui

2014-02-01

Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral infarction compared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway.

PubMed

Wan, Peixing; Su, Wenru; Zhang, Yingying; Li, Zhidong; Deng, Caibin; Zhuo, Yehong

2017-09-15

Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs in vitro TMZ treatment also reduced the production of inflammatory cytokines in vitro Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma. © 2017 The Author(s).

Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

PubMed

Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

2017-03-01

Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice.

PubMed

Bansal, Shruti; Chhibber, Sanjay

2010-04-01

Acute lung injuries due to acute lung infections remain a major cause of mortality. Thus a combination of an antibiotic and a compound with immunomodulatory and anti-inflammatory activities can help to overcome acute lung infection-induced injuries. Curcumin derived from the rhizome of turmeric has been used for decades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatory properties by downregulation of various inflammatory mediators. Keeping these properties in mind, we investigated the anti-inflammatory properties of curcumin in a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillation of bacteria in this mouse model of acute pneumonia-induced inflammation resulted in a significant increase in neutrophil infiltration in the lungs along with increased production of various inflammatory mediators [i.e. malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), tumour necrosis factor (TNF)-alpha] in the lung tissue. The animals that received curcumin alone orally or in combination with augmentin, 15 days prior to bacterial instillation into the lungs via the intranasal route, showed a significant (P <0.05) decrease in neutrophil influx into the lungs and a significant (P <0.05) decrease in the production of MDA, NO, MPO activity and TNF-alpha levels. Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-alpha levels significantly (P >0.05) as compared to the control group. We therefore conclude that curcumin ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, curcumin can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in the case of acute lung infection.

Antiprotozoal, antimycobacterial, and anti-inflammatory evaluation of Cnidoscolus chayamansa (Mc Vaugh) extract and the isolated compounds.

PubMed

Pérez-González, Mariana Z; Gutiérrez-Rebolledo, Gabriel A; Yépez-Mulia, Lilián; Rojas-Tomé, Irma S; Luna-Herrera, Julieta; Jiménez-Arellanes, María A

2017-05-01

Cnidoscolus chayamansa is a medicinal and edible plant known as Chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. In this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the CHCl 3 :MeOH (1:1) leaves extract and isolated compounds, as well as the acute and sub-acute toxic effects. Chemical identification of isolated compounds was performed by 1 H- and 13 C NMR spectra data. In vitro antibacterial and antimycobacterial activities were determined by disc diffusion and MABA assays, respectively; antiprotozoal test by means of the sub-culture test. Topical and systemic anti-inflammatory effects were tested by TPA and carrageenan assay on BALB/c mice. Moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3',4'-trimethoxyflavanone were the main compounds isolated. The CHCl 3 :MeOH extract showed antiprotozoal (IC 50 ≤65.29μg/mL), antimycobacterial (MIC≤50μg/mL), and anti-inflammatory activities (ED 50 =1.66mg/ear and 467.73mg/kg), but was inactive against the bacterial strains tested. The LD 50 for extract was >2g/kg. In the sub-acute toxicity test, the extract was administered at 1g/kg for 28days and did not cause lethality or any alteration in hematological and biochemical parameters; in addition, liver, kidney, and spleen histological analysis exhibited no structural changes. Moretenol and moretenyl acetate showed MIC=25μg/mL against Mycobacterium tuberculosis H37Rv and against four monoresistant strains of M. tuberculosis H37Rv. Both compounds exhibited moderate activity against Entamoeba histolytica and Giardia lamblia (IC 50 ≤71.70μg/mL). Kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxy-flavanone were more active than the extract against E. histolytica and G. lamblia, showing IC 50 ≤27.43μg/mL. As topical anti-inflammatory agents, moretenol and kaempferol-3,7-dimethyl ether were the most active compounds inhibiting the edema in 30.52 and 26.67%, respectively. Moretenol and moretenyl acetate showed significant antimycobacterial and antiprotozoal activities; in addition, important antiprotozoal effect was detected with kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxyflavanone. The extract and the terpenoids possess good anti-inflammatory activity. The extract did not produce lethality or adverse effects in acute and sub-acute tests. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Neuroinflammation in hepatic encephalopathy: mechanistic aspects.

PubMed

Jayakumar, Arumugam R; Rama Rao, Kakulavarapu V; Norenberg, Michael D

2015-03-01

Hepatic encephalopathy (HE) is a major neurological complication of severe liver disease that presents in acute and chronic forms. While elevated brain ammonia level is known to be a major etiological factor in this disorder, recent studies have shown a significant role of neuroinflammation in the pathogenesis of both acute and chronic HE. This review summarizes the involvement of ammonia in the activation of microglia, as well as the means by which ammonia triggers inflammatory responses in these cells. Additionally, the role of ammonia in stimulating inflammatory events in brain endothelial cells (ECs), likely through the activation of the toll-like receptor-4 and the associated production of cytokines, as well as the stimulation of various inflammatory factors in ECs and in astrocytes, are discussed. This review also summarizes the inflammatory mechanisms by which activation of ECs and microglia impact on astrocytes leading to their dysfunction, ultimately contributing to astrocyte swelling/brain edema in acute HE. The role of microglial activation and its contribution to the progression of neurobehavioral abnormalities in chronic HE are also briefly presented. We posit that a better understanding of the inflammatory events associated with acute and chronic HE will uncover novel therapeutic targets useful in the treatment of patients afflicted with HE.

Cold Condition Influence on the Pulmonary Function in Smoking Military Men

DTIC Science & Technology

2002-04-01

abundance, allergy and frequent airways acute inflammatory diseases in anamnesis and have been made routine clinical examination. 23-3 During...physical exercise, emotional stress etc.; and have in anamnesis (during last 2 year) 3-4 times and over acute airway inflammatory diseases: 17 persons

[The relationship between acute inflammatory cytokines, nerve function defect, daily living ability and PSD].

PubMed

Li, Ping; Zhang, Qiao-Lian; Li, Shuang-Ying

2017-02-08

To investigate the correlation between poststroke depression (PSD) and serum levels of inflammatory cytokines, neurologic impairment, daily life ability in patients with acute cerebral infarction at different time. Two hundreds and eighty patients who admitted to our hospital with a diagnosis of acute infarction excluded the patients mismatch conditions were evaluated by Hamilton depres-sion rating scale (HDRS) to diagnose PSD respectively at admission and 3 months after stroke. Serum inflammatory cytokines high-sensitivity C-reactive protein(hs-CRP), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were determined. NIH stroke scale(NIHSS) and Barthel index for daily life ability were used to evaluate nerve functions. Then we analyzed the correlation between PSD and serum inflammatory cytokines, correlation between PSD and functional impairment and daily life ability at different time. Logistic regression was performed to ana-lyze the risk factors of PSD. The PSD incidence was higher in recovery stage than that in acute stage, but there was no difference. Serum inflammatory cytokines were higher in PSD group at admission than that in non-PSD group. The NIHSS score and Barthel index in PSD group were different from those in non-group at acute and recovery stage. The OR score was 1.765, 1.646, 1.817, 1.188 and 2.015 respec-tively to TNF-α, IL-6 and Barthel index in the acute phase and to NIHSS and Barthel index in recovery stage. The pathogenesis of PSD at different courses of stroke is not same. TNF-α, IL-6 and Barthel index are the independent risk factors of PSD in acute phase, so do NIHSS score and Barthel index in recovery period.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

PubMed

Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

Macrophage Sub-Populations and the Lipoxin A4 Receptor Implicate Active Inflammation during Equine Tendon Repair

PubMed Central

Dakin, Stephanie Georgina; Werling, Dirk; Hibbert, Andrew; Abayasekara, Dilkush Robert Ephrem; Young, Natalie Jayne; Smith, Roger Kenneth Whealands; Dudhia, Jayesh

2012-01-01

Macrophages (Mϕ) orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mϕ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured), sub-acute (3–6 weeks post injury) and chronically injured (>3 months post injury) superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mϕ sub-populations were quantified based on surface antigen expression of CD172a (pan Mϕ), CD14highCD206low (pro-inflammatory M1Mϕ), and CD206high (anti-inflammatory M2Mϕ) to assess potential polarised phenotypes. In addition, the Lipoxin A4 receptor (FPR2/ALX) was used as marker for resolving inflammation. Normal tendons were negative for both Mϕ and FPR2/ALX. In contrast, M1Mϕ predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mϕ polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by tenocytes was significantly upregulated in sub-acute but not chronic injury. Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in sub-acute and chronic injuries in contrast to low level expression in normal tendons. The combination of reduced FPR2/ALX expression and persistence of the M2Mϕ phenotype in chronic injury suggests a potential mechanism for incomplete resolution of inflammation after tendon injury. To investigate the effect of pro-inflammatory mediators on lipoxin A4 (LXA4) production and FPR2/ALX expression in vitro, normal tendon explants were stimulated with interleukin-1 beta and prostaglandin E2. Stimulation with either mediator induced LXA4 release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken together, our data suggests that although tenocytes are capable of mounting a protective mechanism to counteract inflammatory stimuli, this appears to be of insufficient duration and magnitude in natural tendon injury, which may potentiate chronic inflammation and fibrotic repair, as indicated by the presence of M2Mϕ. PMID:22384219

Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.

PubMed

Dakin, Stephanie Georgina; Werling, Dirk; Hibbert, Andrew; Abayasekara, Dilkush Robert Ephrem; Young, Natalie Jayne; Smith, Roger Kenneth Whealands; Dudhia, Jayesh

2012-01-01

Macrophages (Mφ) orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mφ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured), sub-acute (3-6 weeks post injury) and chronically injured (>3 months post injury) superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mφ sub-populations were quantified based on surface antigen expression of CD172a (pan Mφ), CD14(high)CD206(low) (pro-inflammatory M1Mφ), and CD206(high) (anti-inflammatory M2Mφ) to assess potential polarised phenotypes. In addition, the Lipoxin A(4) receptor (FPR2/ALX) was used as marker for resolving inflammation. Normal tendons were negative for both Mφ and FPR2/ALX. In contrast, M1Mφ predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mφ polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by tenocytes was significantly upregulated in sub-acute but not chronic injury. Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in sub-acute and chronic injuries in contrast to low level expression in normal tendons. The combination of reduced FPR2/ALX expression and persistence of the M2Mφ phenotype in chronic injury suggests a potential mechanism for incomplete resolution of inflammation after tendon injury. To investigate the effect of pro-inflammatory mediators on lipoxin A(4) (LXA(4)) production and FPR2/ALX expression in vitro, normal tendon explants were stimulated with interleukin-1 beta and prostaglandin E(2). Stimulation with either mediator induced LXA(4) release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken together, our data suggests that although tenocytes are capable of mounting a protective mechanism to counteract inflammatory stimuli, this appears to be of insufficient duration and magnitude in natural tendon injury, which may potentiate chronic inflammation and fibrotic repair, as indicated by the presence of M2Mφ.

Local injections of corticotropin releasing factor reduce doxorubicin-induced acute inflammation in the eyelid.

PubMed

McLoon, L K; Wirtschafter, J

1997-04-01

Doxorubicin chemomyectomy is an effective alternative treatment option for patients with blepharospasm and hemifacial spasm. One side effect of the use of doxorubicin in localized injections is the development of acute inflammation and skin injury at the injection site. Corticotropin releasing factor (CRF) was reported to reduce inflammation after acute inflammatory injuries due to other causes and at other sites. This study was performed to assess the potential of CRF to prevent the development of skin injury and eyelid soreness after local doxorubicin injection. Rabbits received lower eyelid injections of either 75 or 150 micrograms CRF followed by injection of either 0.5, 1, or 2 mg doxorubicin or doxorubicin alone. Eyelids were assessed for changes in acute inflammation by immunohistochemical localization of macrophages and monocytes using anti-CD11, an antibody specific for these cell types. Short-term alterations in vascular permeability were assessed using an Evans blue assay. Additional eyelids were followed daily for changes in the skin over the injection site to determine day of onset of skin injury and the total duration of skin injury. After 1 month, the eyelids were processed histologically for morphometric analysis of muscle fiber loss. Monkey eyelids also were examined for the effect of CRF and doxorubicin injections. Doxorubicin alone produced an acute inflammatory reaction in the treated eyelids, with a large influx of macrophages and monocytes throughout the connective tissue at 1 and 2 days. Corticotropin releasing factor pretreatment significantly reduced this influx of inflammatory cells into the connective tissue. Doxorubicin produced a large increase in vascular permeability in the treated eyelids, with resultant edema. Corticotropin releasing factor did not alter this change in vascular permeability, indicating that CRF appears to have a specific effect on migration of inflammatory cells rather than just a generalized effect on vascular permeability. Corticotropin releasing factor and doxorubicin cotreatments delayed the onset of skin injury and decreased the total duration of injury to the skin compared to doxorubicin alone. The effectiveness of doxorubicin chemomyectomy was maintained; muscle loss was significant at all doses of CRF combined with doxorubicin. Corticotropin releasing factor dramatically decreased the acute inflammatory reaction that results in the eyelid from local doxorubicin injections. Not only did CRF reduce the acute influx of monocytes and macrophages, but it protected the skin overlying the injection site, substantially reducing the extent of skin injury. The efficacy of doxorubicin-induced muscle toxicity was maintained. A treatment protocol that combines myotoxicity with antiinflammatory activity in the treated eyelids may lead to a more effective patient treatment by increasing patient acceptance. The potential should be explored that CRF may be of clinical use in limiting tissue injury when administered immediately after extravasation during cancer chemotherapy.

Splanchnic venous thrombosis and pancreatitis.

PubMed

Nadkarni, Nikhil A; Khanna, Sahil; Vege, Santhi Swaroop

2013-08-01

Pancreatitis is an inflammatory process with local and systemic manifestations. One such local manifestation is thrombosis in splanchnic venous circulation, predominantly of the splenic vein. The literature on this important complication is very sparse. This review offers an overview of mechanism of thrombosis, its pathophysiology, diagnosis, and management in the setting of acute as well as chronic pancreatitis.

Spray-drying process preserves the protective capacity of a breast milk-derived Bifidobacterium lactis strain on acute and chronic colitis in mice

PubMed Central

Burns, Patricia; Alard, Jeanne; Hrdỳ, Jiri; Boutillier, Denise; Páez, Roxana; Reinheimer, Jorge; Pot, Bruno; Vinderola, Gabriel; Grangette, Corinne

2017-01-01

Gut microbiota dysbiosis plays a central role in the development and perpetuation of chronic inflammation in inflammatory bowel disease (IBD) and therefore is key target for interventions with high quality and functional probiotics. The local production of stable probiotic formulations at limited cost is considered an advantage as it reduces transportation cost and time, thereby increasing the effective period at the consumer side. In the present study, we compared the anti-inflammatory capacities of the Bifidobacterium animalis subsp. lactis (B. lactis) INL1, a probiotic strain isolated in Argentina from human breast milk, with the commercial strain B. animalis subsp. lactis BB12. The impact of spray-drying, a low-cost alternative of bacterial dehydration, on the functionality of both bifidobacteria was also investigated. We showed for both bacteria that the spray-drying process did not impact on bacterial survival nor on their protective capacities against acute and chronic colitis in mice, opening future perspectives for the use of strain INL1 in populations with IBD. PMID:28233848

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity

PubMed Central

Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2015-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18–30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. PMID:26316585

Effects of hydrogen sulfide on inflammation in caerulein-induced acute pancreatitis

PubMed Central

2009-01-01

Background Hydrogen sulfide (H2S), a gaseous mediator plays an important role in a wide range of physiological and pathological processes. H2S has been extensively studied for its various roles in cardiovascular and neurological disorders. However, the role of H2S in inflammation is still controversial. The current study was aimed to investigate the therapeutic potential of sodium hydrosulfide (NaHS), an H2S donor in in vivo model of acute pancreatitis in mice. Methods Acute pancreatitis was induced in mice by hourly caerulein injections (50 μg/kg) for 10 hours. Mice were treated with different dosages of NaHS (5 mg/kg, 10 mg/kg or 15 mg/kg) or with vehicle, distilled water (DW). NaHS or DW was administered 1 h before induction of pancreatitis. Mice were sacrificed 1 h after the last caerulein injection. Blood, pancreas and lung tissues were collected and were processed to measure the plasma amylase, myeloperoxidase (MPO) activities in pancreas and lung and chemokines and adhesion molecules in pancreas and lung. Results It was revealed that significant reduction of inflammation, both in pancreas and lung was associated with NaHS 10 mg/kg. Further the anti-inflammatory effects of NaHS 10 mg/kg were associated with reduction of pancreatic and pulmonary inflammatory chemokines and adhesion molecules. NaHS 5 mg/kg did not cause significant improvement on inflammation in pancreas and associated lung injury and NaHS 15 mg/kg did not further enhance the beneficial effects seen with NaHS 10 mg/kg. Conclusion In conclusion, these data provide evidence for anti-inflammatory effects of H2S based on its dosage used. PMID:20040116

ROS-activated calcium signaling mechanisms regulating endothelial barrier function.

PubMed

Di, Anke; Mehta, Dolly; Malik, Asrar B

2016-09-01

Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls

USDA-ARS?s Scientific Manuscript database

Pain management and welfare are increasingly prevalent concerns within animal agriculture and oral analgesics may alleviate the pain associated with castration. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whethe...

Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls

USDA-ARS?s Scientific Manuscript database

Pain management and welfare are increasingly prevalent concerns within animal agriculture. Analgesics may alleviate pain and inflammation associated with castration of beef cattle. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunom...

Effect of surgical castration with or without meloxicam on the acute inflammatory response in yearling beef bulls

USDA-ARS?s Scientific Manuscript database

Pain management and welfare are increasingly prevalent concerns within animal agriculture and oral analgesics may alleviate the pain associated with castration. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whethe...

Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models.

PubMed

Rodrigues, Lindaiane Bezerra; Oliveira Brito Pereira Bezerra Martins, Anita; Cesário, Francisco Rafael Alves Santana; Ferreira E Castro, Fyama; de Albuquerque, Thaís Rodrigues; Martins Fernandes, Maria Neyze; Fernandes da Silva, Bruno Anderson; Quintans Júnior, Lucindo José; da Costa, José Galberto Martins; Melo Coutinho, Henrique Douglas; Barbosa, Roseli; Alencar de Menezes, Irwin Rose

2016-09-25

The genus Ocimum are used in cooking, however, their essential oils are utilized in traditional medicine as aromatherapy. The present study was carried out to investigate the chemical composition and systemic anti-inflammatory activity of the Ocimum basilicum essential oil (EOOB) and its major component estragole, as well as its possible mechanisms of action. The Ocimum basilicum essential oil was obtained by hydrodistillation and analyzed by GC-MS. The anti-inflammatory action was verified using acute and chronic in vivo tests as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was analyzed by the participation of histamine and arachidonic acid pathways. The chemical profile analysis identified fourteen components present in the essential oil, within them: estragole (60.96%). The in vivo test results show that treatment with EOOB (100 and 50 mg/kg) and estragole (60 and 30 mg/kg) significantly reduced paw edema induced by carrageenan and dextran. The smallest doses of EOOB (50 mg/kg) and estragole (30 mg/kg) showed efficacy in the reduction of paw edema induced by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. Theses doses were capable of reducing the chronic inflammatory process. The results observed between the EOOB and estragole demonstrate efficacy in anti-inflammatory activity, however, the essential oil is more efficacious in the acute and chronic anti-inflammatory action. This study confirms the therapeutic potential of this plant and reinforces the validity of its use in popular medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives

PubMed Central

2012-01-01

Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new imidazopyridines with potential therapeutic effects in acute inflammatory diseases. PMID:24900565

Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives.

PubMed

Chen, Gaozhi; Liu, Zhiguo; Zhang, Yali; Shan, Xiaoou; Jiang, Lili; Zhao, Yunjie; He, Wenfei; Feng, Zhiguo; Yang, Shulin; Liang, Guang

2013-01-10

Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new imidazopyridines with potential therapeutic effects in acute inflammatory diseases.

The role of Vitamin D in immuno-inflammatory responses in Ankylosing Spondylitis patients with and without Acute Anterior Uveitis.

PubMed

Mitulescu, T C; Stavaru, C; Voinea, L M; Banica, L M; Matache, C; Predeteanu, D

2016-01-01

Hypothesis: Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim: The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results: 25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS patients without AAU (wAAU AS patients)] and eighteen healthy individuals (Control) using enzyme-linked immunosorbent assay. Acute-phase SAA level was significantly higher in AS patients compared to Controls. Contrary with wAAU AS patients, significantly elevated levels of IL-8, and diminished levels of Vit D characterized AAU AS patients. Regarding LL-37, its level decreased concomitantly with the level of Vit D. When AS patients were subgrouped based on AAU presence or on Vit D level, important associations between immuno-inflammatory assessed markers and AS features were noticed. Generally, Vit D levels were associated indirectly with leukocytes/ neutrophils number or with ESR, CRP, and Fibrinogen levels. The levels of SAA and IL-8 associated directly with AAU or with AAU relapses, especially in AS patients with Vit D insufficiency, while SAA associated directly with infection/ inflammatory markers and with disease activity indexes or with the degree of functional limitation. Discussion: Altered levels of Vit D affect the balance between LL-37, IL-8 and SAA, suggesting an association with AAU, an extra-articular manifestation of AS. Abbreviations: Vit D = Vitamin D, AS = Ankylosing Spondylitis, AAU = Acute Anterior Uveitis, AAU AS = AS patients with AAU, wAAU AS = AS patients without AAU, SSZ = Sulphasalazine, Leu = Leukocytes, Neu = Neutrophils.

The role of Vitamin D in immuno-inflammatory responses in Ankylosing Spondylitis patients with and without Acute Anterior Uveitis

PubMed Central

Mitulescu, TC; Stavaru, C; Voinea, LM; Banica, LM; Matache, C; Predeteanu, D

2016-01-01

Hypothesis:Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim:The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results:25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS patients without AAU (wAAU AS patients)] and eighteen healthy individuals (Control) using enzyme-linked immunosorbent assay. Acute-phase SAA level was significantly higher in AS patients compared to Controls. Contrary with wAAU AS patients, significantly elevated levels of IL-8, and diminished levels of Vit D characterized AAU AS patients. Regarding LL-37, its level decreased concomitantly with the level of Vit D. When AS patients were subgrouped based on AAU presence or on Vit D level, important associations between immuno-inflammatory assessed markers and AS features were noticed. Generally, Vit D levels were associated indirectly with leukocytes/ neutrophils number or with ESR, CRP, and Fibrinogen levels. The levels of SAA and IL-8 associated directly with AAU or with AAU relapses, especially in AS patients with Vit D insufficiency, while SAA associated directly with infection/ inflammatory markers and with disease activity indexes or with the degree of functional limitation. Discussion:Altered levels of Vit D affect the balance between LL-37, IL-8 and SAA, suggesting an association with AAU, an extra-articular manifestation of AS. Abbreviations:Vit D = Vitamin D, AS = Ankylosing Spondylitis, AAU = Acute Anterior Uveitis, AAU AS = AS patients with AAU, wAAU AS = AS patients without AAU, SSZ = Sulphasalazine, Leu = Leukocytes, Neu = Neutrophils. PMID:27713770

Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

PubMed

Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

2014-01-01

Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

PubMed Central

Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

2016-01-01

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury

PubMed Central

Weinreuter, Martin; Kreusser, Michael M; Beckendorf, Jan; Schreiter, Friederike C; Leuschner, Florian; Lehmann, Lorenz H; Hofmann, Kai P; Rostosky, Julia S; Diemert, Nathalie; Xu, Chang; Volz, Hans Christian; Jungmann, Andreas; Nickel, Alexander; Sticht, Carsten; Gretz, Norbert; Maack, Christoph; Schneider, Michael D; Gröne, Hermann-Josef; Müller, Oliver J; Katus, Hugo A; Backs, Johannes

2014-01-01

CaMKII was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic CaMKII mouse models. Although CaMKIIδC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in CaMKIIδ-deficient mice, CaMKIIδ-deficient mice in which the splice variants CaMKIIδB and C were re-expressed, nor in cardiomyocyte-specific CaMKIIδ/γ double knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction, which was associated with reduced leukocyte infiltration and attenuated expression of members of the chemokine (C-C motif) ligand family, in particular CCL3 (macrophage inflammatory protein-1α, MIP-1α). Intriguingly, CaMKII was sufficient and required to induce CCL3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that CaMKII-dependent chemoattractant signaling explains the effects on post-I/R remodeling. Taken together, we demonstrate that CaMKII is not critically involved in acute I/R-induced damage but in the process of post-infarct remodeling and inflammatory processes. PMID:25193973

Toll-like receptors in inflammatory bowel diseases: a decade later.

PubMed

Cario, Elke

2010-09-01

Differential alteration of Toll-like receptor (TLR) expression in inflammatory bowel disease (IBD) was first described 10 years ago. Since then, studies from many groups have led to the current concept that TLRs represent key mediators of innate host defense in the intestine, involved in maintaining mucosal as well as commensal homeostasis. Recent findings in diverse murine models of colitis have helped to reveal the mechanistic importance of TLR dysfunction in IBD pathogenesis. It has become evident that environment, genetics, and host immunity form a multidimensional and highly interactive regulatory triad that controls TLR function in the intestinal mucosa. Imbalanced relationships within this triad may promote aberrant TLR signaling, critically contributing to acute and chronic intestinal inflammatory processes in IBD colitis and associated cancer.

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

NASA Astrophysics Data System (ADS)

Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Spatiotemporal expression dynamics of selectins govern the sequential extravasation of neutrophils and monocytes in the acute inflammatory response.

PubMed

Zuchtriegel, Gabriele; Uhl, Bernd; Hessenauer, Maximilian E T; Kurz, Angela R M; Rehberg, Markus; Lauber, Kirsten; Krombach, Fritz; Reichel, Christoph A

2015-04-01

Leukocyte recruitment to the site of inflammation is a key event in a variety of cardiovascular pathologies. Infiltrating neutrophils constitute the first line of defense that precedes a second wave of emigrating monocytes reinforcing the inflammatory reaction. The mechanisms initiating this sequential process remained largely obscure. Using advanced in vivo microscopy and in vitro/ex vivo techniques, we identified individual spatiotemporal expression patterns of selectins and their principal interaction partners on neutrophils, resident/inflammatory monocytes, and endothelial cells. Coordinating the intraluminal trafficking of neutrophils and inflammatory monocytes to common sites of extravasation, selectins assign different sites to these immune cells for their initial interactions with the microvascular endothelium. Whereas constitutively expressed leukocyte L-selectin/CD62L and endothelial P-selectin/CD62P together with CD44 and P-selectin glycoprotein ligand-1/CD162 initiate the emigration of neutrophils, de novo synthesis of endothelial E-selectin/CD62E launches the delayed secondary recruitment of inflammatory monocytes. In this context, P-selectin/CD62P and L-selectin/CD62L together with P-selectin glycoprotein ligand-1/CD162 and CD44 were found to regulate the flux of rolling neutrophils and inflammatory monocytes, whereas E-selectin/CD62E selectively adjusts the rolling velocity of inflammatory monocytes. Moreover, selectins and their interaction partners P-selectin glycoprotein ligand-1/CD162 and CD44 differentially control the intraluminal crawling behavior of neutrophils and inflammatory monocytes collectively enabling the sequential extravasation of these immune cells to inflamed tissue. Our findings provide novel insights into the mechanisms initiating the sequential infiltration of the perivascular tissue by neutrophils and monocytes in the acute inflammatory response and might thereby contribute to the development of targeted therapeutic strategies for prevention and treatment of cardiovascular diseases. © 2015 American Heart Association, Inc.

Metabolic phenotyping of an adoptive transfer mouse model of experimental colitis and impact of dietary fish oil intake.

PubMed

Martin, Francois-Pierre J; Lichti, Pia; Bosco, Nabil; Brahmbhatt, Viral; Oliveira, Manuel; Haller, Dirk; Benyacoub, Jalil

2015-04-03

Inflammatory bowel diseases are acute and chronic disabling inflammatory disorders with multiple complex etiologies that are not well-defined. Chronic intestinal inflammation has been linked to an energy-deficient state of gut epithelium with alterations in oxidative metabolism. Plasma-, urine-, stool-, and liver-specific metabonomic analyses are reported in a naïve T cell adoptive transfer (AT) experimental model of colitis, which evaluated the impact of long-chain n-3 polyunsaturated fatty acid (PUFA)-enriched diet. Metabolic profiles of AT animals and their controls under chow diet or fish oil supplementation were compared to describe the (i) consequences of inflammatory processes and (ii) the differential impact of n-3 fatty acids. Inflammation was associated with higher glycoprotein levels (related to acute-phase response) and remodeling of PUFAs. Low triglyceride levels and enhanced PUFA levels in the liver suggest activation of lipolytic pathways that could lead to the observed increase of phospholipids in the liver (including plasmalogens and sphingomyelins). In parallel, the increase in stool excretion of most amino acids may indicate a protein-losing enteropathy. Fecal content of glutamine was lower in AT mice, a feature exacerbated under fish oil intervention that may reflect a functional relationship between intestinal inflammatory status and glutamine metabolism. The decrease in Krebs cycle intermediates in urine (succinate, α-ketoglutarate) also suggests a reduction in the glutaminolytic pathway at a systemic level. Our data indicate that inflammatory status is related to this overall loss of energy homeostasis.

Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis.

PubMed

Singh, Shailender; Dallenga, Tobias; Winkler, Anne; Roemer, Shanu; Maruschak, Brigitte; Siebert, Heike; Brück, Wolfgang; Stadelmann, Christine

2017-03-17

Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (Wld S ) mutant mice. The highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in Wld S mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration did not result in a net rescue of axons in late lesion stages of experimental autoimmune encephalomyelitis. Our data indicate that in multiple sclerosis, ongoing demyelination in focal lesions is associated with axonal degeneration in the perilesional white matter, supporting a role for focal pathology in diffuse white matter damage. Also, our results suggest that interfering with Wallerian degeneration in inflammatory demyelination does not suffice to prevent acute axonal damage and finally axonal loss.

Role of inflammation and its mediators in acute ischemic stroke

PubMed Central

Jin, Rong; Liu, Lin; Zhang, Shihao; Nanda, Anil; Li, Guohong

2013-01-01

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies. PMID:24006091

New and Pipeline Drugs for Gout.

PubMed

Keenan, Robert T; Schlesinger, Naomi

2016-06-01

Gout is the most common inflammatory arthropathy in the western world. Affecting millions and accounting for lost wages, increased health care costs, and significant disability, it remains a burden for those afflicted, their families, and the health care system. Despite the availability of a number of effective therapies, gout is often inadequately treated, and its impact on the patients overall health and well-being is underestimated by physicians and patients alike. For many decades, controlling acute flares was the priority in the management of gout. More recently, however, a deeper understanding of gout pathophysiology has resulted in a new appreciation that gout impacts the patient with consequences well beyond the episodes of acute inflammatory arthritis. Reflecting the chronic nature of the disease, gout treatment needs to be chronic as well, and aimed at reducing the underlying cause of gout-hyperuricemia-as well as the symptom of acute attacks. Therapy therefore requires both urate lowering and anti-inflammatory strategies. Unfortunately, the most commonly used urate lowering and anti-inflammatory treatments may be problematic in some gout patients, who often have multiple comorbidities that establish relative contraindications. Novel urate lowering therapies, and new medications to treat and prevent acute gouty flares, can not only improve care of the individual; they can also lead to a better discourse for the edification of those who manage and are managed for this underestimated disease. In this paper, we discuss new and pipeline drugs for acute gout, prophylactic anti-inflammatory therapies as well as urate lowering therapies.

Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats.

PubMed

Nishiyama, Tomoki; Hanaoka, Kazuo

2004-04-01

We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), bupivacaine (1 to 100 microg), or clonidine (0.1 to 3 microg) and tested for their responses to thermal stimulation to the tail (tail flick test) and subcutaneous formalin injection into the hindpaw (formalin test). The effects of the combination of bupivacaine and clonidine on both stimuli were tested by isobolographic analysis. General behavior and motor function were examined as side effects. The 50% effective doses of bupivacaine and clonidine were significantly smaller when combined compared with each single drug in both the tail flick test (2.82 and 0.11 microg versus 7.1 and 0.29 microg, respectively) and phase 1 (0.24 and 0.009 microg versus 5.7 and 0.15 microg) and phase 2 (0.31 and 0.012 microg versus 3.2 and 0.16 microg) of the formalin test. Side effects were decreased by the combination. These results suggest a favorable combination of intrathecal bupivacaine and clonidine in the management of acute and inflammatory pain. The analgesic interaction between intrathecally administered bupivacaine and clonidine was examined during acute thermal and inflammatory-induced pain in rats. The analgesia produced by the combination of these two drugs was synergistic in both acute thermal and inflammatory induced pain, with a decrease in behavioral side effects.

Blood cultures for women hospitalized with acute pelvic inflammatory disease. Are they necessary?

PubMed

Apuzzio, J J; Hessami, S; Rodriguez, P

2001-09-01

To determine the incidence of positive blood cultures and if the results affect the clinical management or the duration of hospital stay in patients with acute pelvic inflammatory disease (PID). Retrospective study of all patients hospitalized with a diagnosis of acute PID from January 1, 1996, to December 31, 1997. Of 93 patients in the study, 3 had significant bacterial growth from blood culture specimens. The results of blood culture specimens did not affect clinical management. Routine specimens for blood culture may not be needed from patients hospitalized with acute PID.

Citral inhibits lipopolysaccharide-induced acute lung injury by activating PPAR-γ.

PubMed

Shen, Yongbin; Sun, Zhanfeng; Guo, Xiaotong

2015-01-15

Citral, a component of lemongrass oil, has been reported to have many pharmacological activities such as anti-bacterial and anti-inflammatory effects. However, the effects of citral on acute lung injury (ALI) and the molecular mechanisms have not been reported. The aim of this study was to detect the effects of citral on lipopolysaccharide (LPS)-induced acute lung injury and investigate the molecular mechanisms. LPS-induced acute lung injury model was used to detect the anti-inflammatory effect of citral in vivo. The alveolar macrophages were used to investigate the molecular mechanism of citral in vitro. The results showed that pretreatment with citral remarkably attenuated pulmonary edema, histological severities, TNF-α, IL-6 and IL-1β production in LPS-induced ALI in vivo. In vitro, citral inhibited LPS-induced TNF-α, IL-6 and IL-1β production in alveolar macrophages. LPS-induced NF-κB activation was also inhibited by citral. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, this is the first to demonstrate that citral protects LPS-induced ALI in mice. The anti-inflammatory mechanism of citral is associated with activating PPAR-γ, thereby inhibiting LPS-induced inflammatory response. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

PubMed

Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

2010-02-18

Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system.

In vivo analysis of THz wave irradiation induced acute inflammatory response in skin by laser-scanning confocal microscopy.

PubMed

Hwang, Yoonha; Ahn, Jinhyo; Mun, Jungho; Bae, Sangyoon; Jeong, Young Uk; Vinokurov, Nikolay A; Kim, Pilhan

2014-05-19

The recent development of THz sources in a wide range of THz frequencies and power levels has led to greatly increased interest in potential biomedical applications such as cancer and burn wound diagnosis. However, despite its importance in realizing THz wave based applications, our knowledge of how THz wave irradiation can affect a live tissue at the cellular level is very limited. In this study, an acute inflammatory response caused by pulsed THz wave irradiation on the skin of a live mouse was analyzed at the cellular level using intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 μs pulsewidth, 61.4 μJ per pulse, 3Hz repetition), generated using compact FEL, was used to irradiate an anesthetized mouse's ear skin with an average power of 260 mW/cm(2) for 30 minutes using a high-precision focused THz wave irradiation setup. In contrast to in vitro analysis using cultured cells at similar power levels of CW THz wave irradiation, no temperature change at the surface of the ear skin was observed when skin was examined with an IR camera. To monitor any potential inflammatory response, resident neutrophils in the same area of ear skin were repeatedly visualized before and after THz wave irradiation using a custom-built laser-scanning confocal microscopy system optimized for in vivo visualization. While non-irradiated control skin area showed no changes in the number of resident neutrophils, a massive recruitment of newly infiltrated neutrophils was observed in the THz wave irradiated skin area after 6 hours, which suggests an induction of acute inflammatory response by the pulsed THz wave irradiation on the skin via a non-thermal process.

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity.

PubMed

Huang, Chun-Jung; Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2016-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18-30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. © 2015 by the Society for Experimental Biology and Medicine.

[Prognosis of acute pancreatitis by PANC 3 score].

PubMed

Fukuda, James Ken; Franzon, Orli; Resende-Filho, Fernando de Oliveira; Kruel, Nicolau Fernandes; Ferri, Thiago Alessandro

2013-06-01

Acute pancreatitis is a disease of great importance in clinical practice, defined as an inflammatory process of the pancreas that may involve local tissues or affect other organs in a systemic manner, requiring, in such cases, an intensive care. To analyze the simplified stratification system of the PANC 3 score, correlating it with the Ranson score, for the prognostic definition of cases of acute pancreatitis. Was conducted a prospective, observational study in which were evaluated 65 patients who were diagnosed with acute pancreatitis. PANC 3 showed sensitivity, 31.25%; specificity,100%; positive predictive value, 100%; negative predictive value, 81.66% and accuracy, 83.07%. The PANC 3 criteria are applicable to define the severity and the prognosis of acute pancreatitis, and are not a substitute method, but rather a method to be associated with the Ranson criteria, mainly due to its high accuracy, positive predictive value and specificity.

Synergistic regulation of the acute phase protein SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines.

PubMed

Liu, Quan-Sheng; Nilsen-Hamilton, Marit; Xiong, Si-Dong

2003-10-25

SIP24/24p3 is a secreted murine acute phase protein which has been speculated to play an anti-inflammatory role in vivo. Recently SIP24/24p3 has been found to be able to specifically induce apoptosis in leukocytes. By using (35)S metabolic labeling method, we studied the regulation of SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines IL-6 and TNF-alpha in cultured Balb/c 3T3 and BNL cells. The following results were observed: (1) dexamethasone induced the expression of SIP24/24p3 in both Balb/c 3T3 and BNL cells, the induction was more significant in BNL cells; (2) dexamethasone and IL-6 synergistically induced the expression of SIP24/24p3 in both Balb/c 3T3 and BNL cells; (3) in Balb/c 3T3 cells dexamethasone and TNF-alpha acted synergistically to induce the expression of SIP24/24p3, whereas in BNL cells dexamethasone and TNF-alpha induced the expression of SIP24/24p3 in an additive manner; (4) dexamethasone and IL-6/TNF-alpha acted synergistically in Balb/c 3T3 cells and additively in BNL cells to induce the expression of SIP24/24p3. The inducibility of SIP24/24p3 by multiple factors will help to explain its highly specific expression in vivo. The difference in the expression patterns of SIP24/24p3 in different cell types is also suggestive to its expression and regulation in hepatic and extrahepatic tissues. Finally, the fact that SIP24/24p3 protein can be induced by both pro-inflammatory as well as anti-inflammatory factors is indicative of the important role of SIP24/24p3 in the entire acute phase response process.

Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice

PubMed Central

Wu, Alex G.; Jaja-Chimedza, Asha; Graf, Brittany L.; Waterman, Carrie; Verzi, Michael P.; Raskin, Ilya

2017-01-01

Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA). Following UC induction, water (vehicle), 150 mg/kg MSE, or 50 mg/kg 5-ASA were orally administered for 1 or 2 wks. Disease activity index (DAI), spleen/colon sizes, and colonic histopathology were measured. From colon and/or fecal samples, pro-inflammatory biomarkers, tight-junction proteins, and Nrf2-mediated enzymes were analyzed at protein and/or gene expression levels. Compared to disease control, MSE decreased DAI scores, and showed an increase in colon lengths and decrease in colon weight/length ratios in both UC models. MSE also reduced colonic inflammation/damage and histopathological scores (modestly) in acute UC. MSE decreased colonic secretions of pro-inflammatory keratinocyte-derived cytokine (KC), tumor necrosis factor (TNF)-α, nitric oxide (NO), and myeloperoxidase (MPO) in acute and chronic UC; reduced fecal lipocalin-2 in acute UC; downregulated gene expression of pro-inflammatory interleukin (IL)-1, IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) in acute UC; upregulated expression of claudin-1 and ZO-1 in acute and chronic UC; and upregulated GSTP1, an Nrf2-mediated phase II detoxifying enzyme, in chronic UC. MSE was effective in mitigating UC symptoms and reducing UC-induced colonic pathologies, likely by suppressing pro-inflammatory biomarkers and increasing tight-junction proteins. This effect is consistent with Nrf2-mediated anti-inflammatory/antioxidant signaling pathway documented for other isothiocyanates similar to MIC-1. Therefore, MSE, enriched with MIC-1, may be useful in prevention and treatment of UC. PMID:28922365

Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice.

PubMed

Kim, Youjin; Wu, Alex G; Jaja-Chimedza, Asha; Graf, Brittany L; Waterman, Carrie; Verzi, Michael P; Raskin, Ilya

2017-01-01

Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA). Following UC induction, water (vehicle), 150 mg/kg MSE, or 50 mg/kg 5-ASA were orally administered for 1 or 2 wks. Disease activity index (DAI), spleen/colon sizes, and colonic histopathology were measured. From colon and/or fecal samples, pro-inflammatory biomarkers, tight-junction proteins, and Nrf2-mediated enzymes were analyzed at protein and/or gene expression levels. Compared to disease control, MSE decreased DAI scores, and showed an increase in colon lengths and decrease in colon weight/length ratios in both UC models. MSE also reduced colonic inflammation/damage and histopathological scores (modestly) in acute UC. MSE decreased colonic secretions of pro-inflammatory keratinocyte-derived cytokine (KC), tumor necrosis factor (TNF)-α, nitric oxide (NO), and myeloperoxidase (MPO) in acute and chronic UC; reduced fecal lipocalin-2 in acute UC; downregulated gene expression of pro-inflammatory interleukin (IL)-1, IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) in acute UC; upregulated expression of claudin-1 and ZO-1 in acute and chronic UC; and upregulated GSTP1, an Nrf2-mediated phase II detoxifying enzyme, in chronic UC. MSE was effective in mitigating UC symptoms and reducing UC-induced colonic pathologies, likely by suppressing pro-inflammatory biomarkers and increasing tight-junction proteins. This effect is consistent with Nrf2-mediated anti-inflammatory/antioxidant signaling pathway documented for other isothiocyanates similar to MIC-1. Therefore, MSE, enriched with MIC-1, may be useful in prevention and treatment of UC.

The effects of acute inflammation on cognitive functioning and emotional processing in humans: A systematic review of experimental studies.

PubMed

Bollen, Jessica; Trick, Leanne; Llewellyn, David; Dickens, Chris

2017-03-01

The cognitive neuropsychological model of depression proposes that negative biases in the processing of emotionally salient information have a central role in the development and maintenance of depression. We have conducted a systematic review to determine whether acute experimental inflammation is associated with changes to cognitive and emotional processing that are thought to cause and maintain depression. We identified experimental studies in which healthy individuals were administered an acute inflammatory challenge (bacterial endotoxin/vaccination) and standardised tests of cognitive function were performed. Fourteen references were identified, reporting findings from 12 independent studies on 345 participants. Methodological quality was rated strong or moderate for 11 studies. Acute experimental inflammation was triggered using a variety of agents (including endotoxin from E. coli, S. typhi, S. abortus Equi and Hepatitis B vaccine) and cognition was assessed over hours to months, using cognitive tests of i) attention/executive functioning, ii) memory and iii) social/emotional processing. Studies found mixed evidence that acute experimental inflammation caused changes to attention/executive functioning (2 of 6 studies showed improvements in attention executive function compared to control), changes in memory (3 of 5 studies; improved reaction time: reduced memory for object proximity: poorer immediate and delayed memory) and changes to social/emotional processing (4 of 5 studies; reduced perception of emotions, increased avoidance of punishment/loss experiences, and increased social disconnectedness). Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Complement Activation Alters Platelet Function

DTIC Science & Technology

2015-12-01

haemostatic and coagulation properties of platelets. 15. SUBJECT TERMS Platelets, Complement, Trauma, Tissue Damage 16. SECURITY CLASSIFICATION... coagulation , there is mounting evidence that they may also be important in the development and progression of inflammatory processes (Coppinger et al...receptor-ligand interactions and/or through exposure to cytokines including IL-6, other acute-phase reactants, and pro- coagulant factors such as thrombin

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

PubMed

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

2013-01-01

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

Acute Phase Proteins and Their Role in Periodontitis: A Review

PubMed Central

Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

2015-01-01

Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

Inflammation-induced proteolytic processing of the SIRPα cytoplasmic ITIM in neutrophils propagates a proinflammatory state

PubMed Central

Zen, Ke; Guo, Yalan; Bian, Zhen; Lv, Zhiyuan; Zhu, Dihan; Ohnishi, Hiroshi; Matozaki, Takashi; Liu, Yuan

2018-01-01

Signal regulatory protein α (SIRPα), an immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor, is an essential negative regulator of leukocyte inflammatory responses. Here we report that SIRPα cytoplasmic signalling ITIMs in neutrophils are cleaved during active inflammation and that the loss of SIRPα ITIMs enhances the polymorphonuclear leukocyte (PMN) inflammatory response. Using human leukocytes and two inflammatory models in mice, we show that the cleavage of SIRPα ITIMs in PMNs but not monocytes occurs at the post-acute stage of inflammation and correlates with increased PMN recruitment to inflammatory loci. Enhanced transmigration of PMNs and PMN-associated tissue damage are confirmed in mutant mice expressing SIRPα but lacking the ITIMs. Moreover, the loss of SIRPα ITIMs in PMNs during colitis is blocked by an anti-interleukin-17 (IL-17) antibody. These results demonstrate a SIRPα-based mechanism that dynamically regulates PMN inflammatory responses by generating a CD47-binding but non-signalling SIRPα ‘decoy’. PMID:24026300

Quantification of structural changes in acute inflammation by fractal dimension, angular second moment and correlation.

PubMed

Stankovic, Marija; Pantic, Igor; De Luka, Silvio R; Puskas, Nela; Zaletel, Ivan; Milutinovic-Smiljanic, Sanja; Pantic, Senka; Trbovich, Alexander M

2016-03-01

The aim of the study was to examine alteration and possible application of fractal dimension, angular second moment, and correlation for quantification of structural changes in acutely inflamed tissue. Acute inflammation was induced by injection of turpentine oil into the right and left hind limb muscles of mice, whereas control animals received intramuscular saline injection. After 12 h, animals were anesthetised and treated muscles collected. The tissue was stained by hematoxylin and eosin, digital micrographs produced, enabling determination of fractal dimension of the cells, angular second moment and correlation of studied tissue. Histopathological analysis showed presence of inflammatory infiltrate and tissue damage in inflammatory group, whereas tissue structure in control group was preserved, devoid of inflammatory infiltrate. Fractal dimension of the cells, angular second moment and correlation of treated tissue in inflammatory group decreased in comparison to the control group. In this study, we were first to observe and report that fractal dimension of the cells, angular second moment, and correlation were reduced in acutely inflamed tissue, indicating loss of overall complexity of the cells in the tissue, the tissue uniformity and structure regularity. Fractal dimension, angular second moment and correlation could be useful methods for quantification of structural changes in acute inflammation. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

A comparative analysis of acute-phase proteins as inflammatory biomarkers in preclinical toxicology studies: implications for preclinical to clinical translation.

PubMed

Watterson, Claire; Lanevschi, Anne; Horner, Judith; Louden, Calvert

2009-01-01

Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential human hazards. In vitro screens with human cells, though promising, need further development. Therefore, identification of improved preclinical diagnostic markers of SIRS will enable clinicians to select applicable markers for clinical testing and avoid potentially catastrophic events. There is limited preclinical toxicology data describing the interspecies performance of acute-phase proteins because the response time, type, and duration of major acute-phase proteins vary significantly between species. This review will attempt to address this intellectual gap, as well as the use and applicability of acute-phase proteins as preclinical to clinical translational biomarkers of SIRS.

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

PubMed

Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

2018-01-01

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Stress-dependent changes in neuroinflammatory markers observed after common laboratory stressors are not seen following acute social defeat of the Sprague Dawley rat.

PubMed

Hueston, Cara M; Barnum, Christopher J; Eberle, Jaime A; Ferraioli, Frank J; Buck, Hollin M; Deak, Terrence

2011-08-03

Exposure to acute stress has been shown to increase the expression of pro-inflammatory cytokines in brain, blood and peripheral organs. However, the nature of the inflammatory response evoked by acute stress varies depending on the stressor used and species examined. The goal of the following series of studies was to characterize the consequences of social defeat in the Sprague Dawley (SD) rat using three different social defeat paradigms. In Experiments 1 and 2, adult male SD rats were exposed to a typical acute resident-intruder paradigm of social defeat (60 min) by placement into the home cage of a larger, aggressive Long Evans rat and brain tissue was collected at multiple time points for analysis of IL-1β protein and gene expression changes in the PVN, BNST and adrenal glands. In subsequent experiments, rats were exposed to once daily social defeat for 7 or 21 days (Experiment 3) or housed continuously with an aggressive partner (separated by a partition) for 7 days (Experiment 4) to assess the impact of chronic social stress on inflammatory measures. Despite the fact that social defeat produced a comparable corticosterone response as other stressors (restraint, forced swim and footshock; Experiment 5), acute social defeat did not affect inflammatory measures. A small but reliable increase in IL-1 gene expression was observed immediately after the 7th exposure to social defeat, while other inflammatory measures were unaffected. In contrast, restraint, forced swim and footshock all significantly increased IL-1 gene expression in the PVN; other inflammatory factors (IL-6, cox-2) were unaffected in this structure. These findings provide a comprehensive evaluation of stress-dependent inflammatory changes in the SD rat, raising intriguing questions regarding the features of the stress challenge that may be predictive of stress-dependent neuroinflammation. Copyright © 2011 Elsevier Inc. All rights reserved.

Necroptosis: a potential, promising target and switch in acute pancreatitis.

PubMed

Wang, Gang; Qu, Feng-Zhi; Li, Le; Lv, Jia-Chen; Sun, Bei

2016-02-01

Pancreatic acinar cell death is the major pathophysiological change in early acute pancreatitis (AP), and the death modalities are important factors determining its progression and prognosis. During AP, acinar cells undergo two major modes of death, including necrosis and apoptosis. Acinar necrosis can lead to intensely local and systemic inflammatory responses, which both induce and aggravate the lesion. Necrosis has long been considered an unregulated, and passive cell death process. Since the effective interventions of necrosis are difficult to perform, its relevant studies have not received adequate attention. Necroptosis is a newly discovered cell death modality characterized by both necrosis and apoptosis, i.e., it is actively regulated by special genes, while has the typical morphological features of necrosis. Currently, necroptosis is gradually becoming an important topic in the fields of inflammatory diseases. The preliminary results from necroptosis in AP have confirmed the existence of acinar cell necroptosis, which may be a potential target for effectively regulating inflammatory injuries and improving its outcomes; however, the functional changes and mechanisms of necroptosis still require further investigation. This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets.

Update on pathogenesis and clinical management of acute pancreatitis

PubMed Central

Cruz-Santamaría, Dulce M; Taxonera, Carlos; Giner, Manuel

2012-01-01

Acute pancreatitis (AP), defined as the acute nonbacterial inflammatory condition of the pancreas, is derived from the early activation of digestive enzymes found inside the acinar cells, with variable compromise of the gland itself, nearby tissues and other organs. So, it is an event that begins with pancreatic injury, elicits an acute inflammatory response, encompasses a variety of complications and generally resolves over time. Different conditions are known to induce this disorder, although the innermost mechanisms and how they act to develop the disease are still unknown. We summarize some well established aspects. A phase sequence has been proposed: etiology factors generate other conditions inside acinar cells that favor the AP development with some systemic events; genetic factors could be involved as susceptibility and modifying elements. AP is a disease with extremely different clinical expressions. Most patients suffer a mild and limited disease, but about one fifth of cases develop multi organ failure, accompanied by high mortality. This great variability in presentation, clinical course and complications has given rise to the confusion related to AP related terminology. However, consensus meetings have provided uniform definitions, including the severity of the illness. The clinical management is mainly based on the disease´s severity and must be directed to correct the underlying predisposing factors and control the inflammatory process itself. The first step is to determine if it is mild or severe. We review the principal aspects to be considered in this treatment, as reflected in several clinical practice guidelines. For the last 25 years, there has been a global increase in incidence of AP, along with many advances in diagnosis and treatment. However, progress in knowledge of its pathogenesis is scarce. PMID:22737590

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

PubMed Central

Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-01-01

Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain. PMID:27559448

Analysis of adrenocortical secretory responses during acute an prolonged immune stimulation in inflammation-susceptible and -resistant rat strains.

PubMed

Andersson, I M; Lorentzen, J C; Ericsson-Dahlstrand, A

2000-11-01

Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine-immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation-susceptible Dark Agouti (DA) rats and resistant, MHC-identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast beta-glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of beta-glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan-injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1-30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, beta-glucan-challenged DA rats responded with an aggravated arthritic process, indicating an anti-inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with beta-glucan. Moreover, substitution with subcutaneous corticosterone-secreting pellets, yielding moderate stress-levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan-challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone-independent mechanisms. In conclusion, the hypothalamic-pituitary-adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal corticosterone levels observed strains during a prolonged arthritic process. No correlation between ability to secrete corticosterone and susceptibility to inflammation could be demonstrated. Basal levels of endogenous corticosterone appeared to restrain inflammation in beta-glucan-challenged DA rats whereas resistance to inflammation in PVG.1AV1 rats may be mediated via corticosterone-independent mechanisms.

Design, synthesis, and structure-activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury.

PubMed

Xiao, Siyang; Zhang, Wenxin; Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

2018-01-01

The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f , was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury.

Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

PubMed

Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

2009-03-17

The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I.

Anti-inflammatory activity of Odina wodier Roxb, an Indian folk remedy, through inhibition of toll-like receptor 4 signaling pathway.

PubMed

Ojha, Durbadal; Mukherjee, Hemanta; Mondal, Supriya; Jena, Aditya; Dwivedi, Ved Prakash; Mondal, Keshab C; Malhotra, Bharti; Samanta, Amalesh; Chattopadhyay, Debprasad

2014-01-01

Inflammation is part of self-limiting non-specific immune response, which occurs during bodily injury. In some disorders the inflammatory process becomes continuous, leading to the development of chronic inflammatory diseases including cardiovascular diseases, diabetes, cancer etc. Several Indian tribes used the bark of Odina wodier (OWB) for treating inflammatory disorders. Thus, we have evaluated the immunotherapeutic potential of OWB methanol extract and its major constituent chlorogenic acid (CA), using three popular in vivo antiinflammatory models: Carrageenan- and Dextran-induced paw edema, Cotton pellet granuloma, and Acetic acid-induced vascular permeability. To elucidate the possible anti-inflammatory mechanism of action we determine the level of major inflammatory mediators (NO, iNOS, COX-2-dependent prostaglandin E2 or PGE2), and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12). Further, we determine the toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88), c-Jun N-terminal kinases (JNK), nuclear factor kappa-B cells (NF-κB), and NF-kB inhibitor alpha (IK-Bα) by protein and mRNA expression, and Western blot analysis in drug treated LPS-induced murine macrophage model. Moreover, we determined the acute and sub-acute toxicity of OWB extract in BALB/c mice. Our study demonstrated a significant anti-inflammatory activity of OWB extract and CA along with the inhibition of TNF-α, IL-1β, IL-6 and IL-12 expressions. Further, the expression of TLR4, NF-κBp65, MyD88, iNOS and COX-2 molecules were reduced in drug-treated groups, but not in the LPS-stimulated untreated or control groups, Thus, our results collectively indicated that the OWB extract and CA can efficiently inhibit inflammation through the down regulation of TLR4/MyD88/NF-kB signaling pathway.

Anti-Inflammatory Activity of Odina wodier Roxb, an Indian Folk Remedy, through Inhibition of Toll-Like Receptor 4 Signaling Pathway

PubMed Central

Ojha, Durbadal; Mukherjee, Hemanta; Mondal, Supriya; Jena, Aditya; Dwivedi, Ved Prakash; Mondal, Keshab C.; Malhotra, Bharti; Samanta, Amalesh; Chattopadhyay, Debprasad

2014-01-01

Inflammation is part of self-limiting non-specific immune response, which occurs during bodily injury. In some disorders the inflammatory process becomes continuous, leading to the development of chronic inflammatory diseases including cardiovascular diseases, diabetes, cancer etc. Several Indian tribes used the bark of Odina wodier (OWB) for treating inflammatory disorders. Thus, we have evaluated the immunotherapeutic potential of OWB methanol extract and its major constituent chlorogenic acid (CA), using three popular in vivo antiinflammatory models: Carrageenan- and Dextran-induced paw edema, Cotton pellet granuloma, and Acetic acid-induced vascular permeability. To elucidate the possible anti-inflammatory mechanism of action we determine the level of major inflammatory mediators (NO, iNOS, COX-2-dependent prostaglandin E2 or PGE2), and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12). Further, we determine the toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88), c-Jun N-terminal kinases (JNK), nuclear factor kappa-B cells (NF-κB), and NF-kB inhibitor alpha (IK-Bα) by protein and mRNA expression, and Western blot analysis in drug treated LPS-induced murine macrophage model. Moreover, we determined the acute and sub-acute toxicity of OWB extract in BALB/c mice. Our study demonstrated a significant anti-inflammatory activity of OWB extract and CA along with the inhibition of TNF-α, IL-1β, IL-6 and IL-12 expressions. Further, the expression of TLR4, NF-κBp65, MyD88, iNOS and COX-2 molecules were reduced in drug-treated groups, but not in the LPS-stimulated untreated or control groups, Thus, our results collectively indicated that the OWB extract and CA can efficiently inhibit inflammation through the down regulation of TLR4/MyD88/NF-kB signaling pathway. PMID:25153081

[Study on baking processing technology of hui medicine Aconitum flavum].

PubMed

Fu, Xue-yan; Zhang, Bai-tong; Li, Ting-ting; Dong, Lin; Hao, Wen-jing; Yu, Liang

2013-12-01

To screen and optimize the processing technology of Aconitum flavum. The acute-toxicity, anti-inflammatory and analgesic experiments were used as indexes. Four processing methods, including decoction, streaming, baking and processing with Chebulae Fructus decoction, were compared to screen the optimum processing method for Aconitum flavum. The baking time was also optimized. The optimal baked technology was that 1-2 mm decoction pieces was baked at 105 degrees C for 3 hours. The baking method is proved to be the optimal processing method of Aconitum flavum. It is shown that this method is simple and stable.

Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models

PubMed Central

Matsui, Mariko; Roche, Louise; Geroult, Sophie; Soupé-Gilbert, Marie-Estelle; Monchy, Didier; Huerre, Michel; Goarant, Cyrille

2016-01-01

Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. Humans can be infected after exposure to contaminated urine of reservoir animals, usually rodents, regarded as typical asymptomatic carriers of leptospires. In contrast, accidental hosts may present an acute form of leptospirosis with a range of clinical symptoms including the development of Acute Kidney Injury (AKI). Chronic Kidney Disease (CKD) is considered as a possible AKI-residual sequela but little is known about the renal pathophysiology consequent to leptospirosis infection. Herein, we studied the renal morphological alterations in relation with the regulation of inflammatory cytokines and chemokines, comparing two experimental models of chronic leptospirosis, the golden Syrian hamster that survived the infection, becoming carrier of virulent leptospires, and the OF1 mouse, a usual reservoir of the bacteria. Animals were monitored until 28 days after injection with a virulent L. borgpetersenii serogroup Ballum to assess chronic infection. Hamsters developed morphological alterations in the kidneys with tubulointerstitial nephritis and fibrosis. Grading of lesions revealed higher scores in hamsters compared to the slight alterations observed in the mouse kidneys, irrespective of the bacterial load. Interestingly, pro-fibrotic TGF-β was downregulated in mouse kidneys. Moreover, cytokines IL-1β and IL-10, and chemokines MIP-1α/CCL3 and IP-10/CXCL-10 were significantly upregulated in hamster kidneys compared to mice. These results suggest a possible maintenance of inflammatory processes in the hamster kidneys with the infiltration of inflammatory cells in response to bacterial carriage, resulting in alterations of renal tissues. In contrast, lower expression levels in mouse kidneys indicated a better regulation of the inflammatory response and possible resolution processes likely related to resistance mechanisms. PMID:27219334

Protective Action of Se-Supplement Against Acute Alcoholism Is Regulated by Selenoprotein P (SelP) in the Liver.

PubMed

Zhang, Zhenbiao; Guo, Yingfang; Qiu, Changwei; Deng, Ganzhen; Guo, Mengyao

2017-02-01

Acute alcoholism is a major cause of cirrhosis and liver failure around the world. Selenium (Se) is an essential micronutrient promoting liver health in humans and animals. Selenoprotein P (SelP) is a glycoprotein secreted within the liver, which interacts with cytokines and the growth factor pathway to provide protection for hepatic cells. The present study was conducted to confirm the effect and mechanism of Se and SelP action in livers affected by acute alcoholism. In this study, a mouse model of acute alcoholism, as well as a hepatocyte model, was successfully established. The Se content of the liver was detected by atomic fluorescence spectrophotometry. The expression of messenger RNA (mRNA) was analyzed by quantitative polymerase chain reaction (qPCR). The protein expression of inflammatory factors was detected by ELISA. The other proteins were analyzed by western blotting. The results showed that pathological damage to the liver was gradually weakened by Se-supplementation, which was evaluated by hematoxylin and eosin (H&E) and TUNEL staining. Se-supplementation inhibited expression of pro-inflammatory factors TNF-α and IL-1β and promoted production of anti-inflammatory cytokine IL-10 in the liver with acute alcoholism. Se-supplementation also prevented the apoptosis of hepatocytes by suppressing the cleavage of caspases-9, 3, 6, 7, and poly(ADP-ribose) polymerase (PARP). Through correlational analysis, it was determined that the effects of Se-supplement were closely related to SelP expression, inflammatory cytokines, and apoptosis molecule production. The sienna of SelP further confirmed the protective action of Se-supplementation on the liver and that the mechanism of SelP involves the regulation of inflammatory cytokines and apoptosis molecules in acute alcoholism. These findings provide information regarding a new potential target for the treatment of acute alcoholism.

Toll-like receptors in inflammatory bowel diseases: A decade later

PubMed Central

Cario, Elke

2010-01-01

Differential alteration of Toll-like receptor (TLR) expression in inflammatory bowel disease (IBD) was first described 10 years ago. Since then, studies from many groups have led to the current concept that TLRs represent key mediators of innate host defense in the intestine, involved in maintaining mucosal as well as commensal homeostasis. Recent findings in diverse murine models of colitis have helped to reveal the mechanistic importance of TLR dysfunction in IBD pathogenesis. It has become evident that environment, genetics, and host immunity form a multidimensional and highly interactive regulatory triad that controls TLR function in the intestinal mucosa. Imbalanced relationships within this triad may promote aberrant TLR signaling, critically contributing to acute and chronic intestinal inflammatory processes in IBD colitis and associated cancer. (Inflamm Bowel Dis 2010) PMID:20803699

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs.

PubMed

Nogueira-Paiva, Nívia Carolina; Fonseca, Kátia da Silva; Vieira, Paula Melo de Abreu; Diniz, Lívia Figueiredo; Caldas, Ivo Santana; Moura, Sandra Aparecida Lima de; Veloso, Vanja Maria; Guedes, Paulo Marcos da Matta; Tafuri, Washington Luiz; Bahia, Maria Terezinha; Carneiro, Cláudia Martins

2014-02-01

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

Participation of satellite glial cells of the dorsal root ganglia in acute nociception.

PubMed

Lemes, Júlia Borges Paes; de Campos Lima, Tais; Santos, Débora Oliveira; Neves, Amanda Ferreira; de Oliveira, Fernando Silva; Parada, Carlos Almicar; da Cruz Lotufo, Celina Monteiro

2018-05-29

At dorsal root ganglia, neurons and satellite glial cells (SGC) can communicate through ATP release and P2X7 receptor activation. SGCs are also interconnected by gap junctions and have been previously implicated in modulating inflammatory and chronic pain.We now present evidence that SGCs are also involved in processing acute nociception in rat dorsal root ganglia. Using primary dorsal root ganglia cultures we observed that calcium transients induced in neurons by capsaicin administration were followed by satellite glial cells activation. Only satellite glial cells response was reduced by administration of the P2X7 receptor antagonist A740003. In vivo, acute nociception induced by intraplantar injection of capsaicin in rats was inhibited by A740003 or by the gap junction blocker carbenoxolone administered at the dorsal root ganglia (L5 level). Both drugs also reduced the second phase of the formalin test. These results suggest that communication between neurons and satellite glial cells is not only involved in inflammatory or pathological pain, but also in the transmission of the nociceptive signal, possibly in situations involving C-fiber activation. Copyright © 2018 Elsevier B.V. All rights reserved.

Neutrophil Extracellular Traps: Formation and Involvement in Disease Progression.

PubMed

Kumar, Sanni; Gupta, Ena; Kaushik, Sanket; Jyoti, Anupam

2018-06-01

Neutrophils are the forerunner in innate immunity by defending the host organisms against infectious pathogens. During such process, neutrophils reach the site of inflammation/infection and eliminate the pathogens by phagocytosis as well as by forming the neutrophil extracellular traps (NETs). NETs trap and eradicate a number of microbes including bacteria, fungi, protozoa, viruses. NETs consist of DNA which is decorated with histones and granular proteins such as neutrophil elastase (NE), gelatinase, myeloperoxidase. NETosis (a process of NETs formation) is also involved in many inflammatory and autoimmune disorders with a major contribution to acute respiratory distress syndrome, sepsis, cystic fibrosis, periodontitis. Hyper NETosis or ineffective clearance of NETs would likely increase the risk of auto-antibody generation against NETs components and contribution in auto-inflammatory diseases. The purpose of this review is intended to highlight the molecular mechanisms of NETosis and its antimicrobial effect. Furthermore, a current status of NETosis in the pathogenesis of inflammatory and autoimmune disorders has been reviewed for better understanding.

Esophageal Xanthoma: Presence of M2 Macrophages Suggests Association with Late Inflammatory and Reparative Processes

PubMed Central

Uehara, Karina; Iwashita, Hidehiko; Tanabe, Yasuka; Kurima, Kiyoto; Oshiro, Mariko; Kina, Shinichiro; Ota, Atsuko; Iwashita, Akinori; Kinjo, Takao

2017-01-01

Abstract Esophageal xanthoma is a rare lesion which is an asymptomatic small yellowish polyp, and most of the reported cases were solitary lesion. Histologically, aggregations of foam cells are found under the papillary hypertrophic squamous epithelium and the foam cells express CD68. The etiology of esophageal xanthoma is unknown. The focal irritation of the esophageal mucosa and infiltrated inflammatory cells are presumed to contribute to its pathogenesis. Although the pathogenesis may be associated with inflammation, the type and nature of the macrophages remain unclear. Here we report a 46-year-old male with esophageal xanthoma, which was incidentally found by endoscopy. Histologically, acute inflammation was not noted, and immunohistochemistry revealed that the foam cells seen in this case of esophageal xanthoma expressed increased levels of M2 macrophage markers. These findings suggest that esophageal xanthoma is associated with late inflammatory and reparative processes long after the initial inflammation of esophageal squamous epithelium. PMID:29071304

Case of concurrent Riedel's thyroiditis, acute suppurative thyroiditis, and micropapillary carcinoma.

PubMed

Hong, Ji Taek; Lee, Jung Hwan; Kim, So Hun; Hong, Seong Bin; Nam, Moonsuk; Kim, Yong Seong; Chu, Young Chae

2013-03-01

Riedel's thyroiditis (RT) is a rare chronic inflammatory disease of the thyroid gland. It is characterized by a fibroinflammatory process that partially destroys the gland and extends into adjacent neck structures. Its clinical manifestation can mask an accompanying thyroid neoplasm and can mimic invasive thyroid carcinoma. Therefore, diagnosis can be difficult prior to surgical removal of the thyroid, and histopathologic examination of the thyroid is necessary for a definite diagnosis. The concurrent presence of RT and other thyroid diseases has been reported. However, to our knowledge, the association of RT with acute suppurative thyroiditis and micropapillary carcinoma has not been reported. We report a rare case of concurrent RT, acute suppurative thyroiditis, and micropapillary carcinoma in a 48-year-old patient.

Acute pancreatitis at the beginning of the 21st century: The state of the art

PubMed Central

Tonsi, Alfredo F; Bacchion, Matilde; Crippa, Stefano; Malleo, Giuseppe; Bassi, Claudio

2009-01-01

Acute pancreatitis is an acute inflammatory disease of the pancreas which can lead to a systemic inflammatory response syndrome with significant morbidity and mortality in 20% of patients. Gallstones and alcohol consumption are the most frequent causes of pancreatitis in adults. The treatment of mild acute pancreatitis is conservative and supportive; however severe episodes characterized by necrosis of the pancreatic tissue may require surgical intervention. Advanced understanding of the pathology, and increased interest in assessment of disease severity are the cornerstones of future management strategies of this complex and heterogeneous disease in the 21st century. PMID:19554647

[Acute severe colitis with recto-vaginal fistula during treatment with non-steroidal anti-inflammatory agents].

PubMed

Tissot, B; Lamy, A; Perraudeau, F; Manouvrier, J L; Imbert, Y

2002-07-13

We report the case of severe colitis occurring during treatment with non-steroid anti-inflammatories (NSAI). A 57 year-old woman was hospitalized for lumbar pain that had not been relieved by AINS, tramadol and then morphine. The patient presented with septic shock and peritonitis by rectal perforation, followed by acute rectorrhagia. The endoscopic aspect evoked Crohn's disease with a recto-vaginal fistula. Progression was further complicated by two episodes of collapse because of acute rectorrhagia, requiring hemostasis colectomy and abdominal-perineal amputation. The diagnosis retained was AINS-induced colitis complicated by acute colectasia on a fecaloma with recto-vaginal fistula.

Gamma-Terpinene Modulates Acute Inflammatory Response in Mice.

PubMed

Ramalho, Theresa Raquel de Oliveira; Oliveira, Maria Talita Pacheco de; Lima, Ana Luisa de Araujo; Bezerra-Santos, Claudio Roberto; Piuvezam, Marcia Regina

2015-09-01

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1β and tumor necrosis factor-α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. Georg Thieme Verlag KG Stuttgart · New York.

Pituitary adenylate cyclase-activating polypeptide ameliorates experimental acute ileitis and extra-intestinal sequelae.

PubMed

Heimesaat, Markus M; Dunay, Ildiko R; Schulze, Silvia; Fischer, André; Grundmann, Ursula; Alutis, Marie; Kühl, Anja A; Tamas, Andrea; Toth, Gabor; Dunay, Miklos P; Göbel, Ulf B; Reglodi, Dora; Bereswill, Stefan

2014-01-01

The neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP) plays pivotal roles in immunity and inflammation. So far, potential immune-modulatory properties of PACAP have not been investigated in experimental ileitis. Mice were perorally infected with Toxoplasma (T.) gondii to induce acute ileitis (day 0) and treated daily with synthetic PACAP38 from day 1 to 6 post infection (p.i.; prophylaxis) or from day 4 to 6 p.i. (therapy). Whereas placebo-treated control mice suffered from acute ileitis at day 7 p.i. and succumbed to infection, intestinal immunopathology was ameliorated following PACAP prophylaxis. PACAP-treated mice exhibited increased abundance of small intestinal FOXP3+ cells, but lower numbers of ileal T lymphocytes, neutrophils, monocytes and macrophages, which was accompanied by less ileal expression of pro-inflammatory cytokines such as IL-23p19, IL-22, IFN-γ, and MCP-1. Furthermore, PACAP-treated mice displayed higher anti-inflammatory IL-4 concentrations in mesenteric lymph nodes and liver and higher systemic anti-inflammatory IL-10 levels in spleen and serum as compared to control animals at day 7 p.i. Remarkably, PACAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments as indicated by reduced pro-inflammatory mediator levels in spleen (TNF-α, nitric oxide) and liver (TNF-α, IFN-γ, MCP-1, IL-6) and less severe histopathological sequelae in lungs and kidneys following prophylactic PACAP treatment. Strikingly, PACAP prolonged survival of T. gondii infected mice in a time-of-treatment dependent manner. Synthetic PACAP ameliorates acute small intestinal inflammation and extra-intestinal sequelae by down-regulating Th1-type immunopathology, reducing oxidative stress and up-regulating anti-inflammatory cytokine responses. These findings provide novel potential treatment options of inflammatory bowel diseases.

New probiotic strains for inflammatory bowel disease management identified by combining in vitro and in vivo approaches.

PubMed

Alard, J; Peucelle, V; Boutillier, D; Breton, J; Kuylle, S; Pot, B; Holowacz, S; Grangette, C

2018-02-27

Alterations in the gut microbiota composition play a key role in the development of chronic diseases such as inflammatory bowel disease (IBD). The potential use of probiotics therefore gained attention, although outcomes were sometimes conflicting and results largely strain-dependent. The present study aimed to identify new probiotic strains that have a high potential for the management of this type of pathologies. Strains were selected from a large collection by combining different in vitro and in vivo approaches, addressing both anti-inflammatory potential and ability to improve the gut barrier function. We identified six strains with an interesting anti-inflammatory profile on peripheral blood mononuclear cells and with the ability to restore the gut barrier using a gut permeability model based on Caco-2 cells sensitized with hydrogen peroxide. The in vivo evaluation in two 2,4,6-trinitrobenzene sulfonic acid-induced murine models of colitis highlighted that some of the strains exhibited beneficial activities against acute colitis while others improved chronic colitis. Bifidobacterium bifidum PI22, the strain that exhibited the most protective capacities against acute colitis was only slightly efficacious against chronic colitis, while Bifidobacterium lactis LA804 which was less efficacious in the acute model was the most protective against chronic colitis. Lactobacillus helveticus PI5 was not anti-inflammatory in vitro but the best in strengthening the epithelial barrier and as such able to significantly dampen murine acute colitis. Interestingly, Lactobacillus salivarius LA307 protected mice significantly against both types of colitis. This work provides crucial clues for selecting the best strains for more efficacious therapeutic approaches in the management of chronic inflammatory diseases. The strategy employed allowed us to identify four strains with different characteristics and a high potential for the management of inflammatory diseases, such as IBD.

Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

PubMed Central

2016-01-01

We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

Cold-Induced Browning Dynamically Alters the Expression Profiles of Inflammatory Adipokines with Tissue Specificity in Mice.

PubMed

Luo, Xiao; Jia, Ru; Zhang, Qiangling; Sun, Bo; Yan, Jianqun

2016-05-23

Cold exposure or β₃-adrenoceptor agonist treatment induces the adipose tissues remodeling, relevant for beige adipogenesis within white adipose tissue (WAT). It remains unclear whether this process influences inflammatory adipokines expression in adipose tissues. We determine the temporal profile of cold or β₃-adrenoceptor agonist (CL316,243)-induced changes in the expression of inflammatory adipokines in adipose tissues in mice or primary mice adipocytes. Male C57BL/6J mice at eight weeks old were exposed to 4 °C for 1-5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous WAT (sWAT) and epididymal WAT (eWAT) were harvested for gene and protein expression analysis. In addition, cultured primary mice brown adipocyte (BA) and white adipocyte (WA) treated with or without CL316,243 were harvested for gene expression analysis. The inflammatory adipokines expressed significantly higher in WAT than BAT at baseline. They were rapidly changed in iBAT, while down-regulated in sWAT and up-regulated in eWAT during the cold acclimation. Upon CL316,243 treatment, detected inflammatory adipokines except Leptin were transiently increased in both BA and WA. Our in vivo and in vitro data demonstrate that the browning process alters the inflammatory adipokines expression in adipose tissues, which is acutely responded to in iBAT, dynamically decreased in sWAT whilst increased in eWAT for compensation.

The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes.

PubMed

Watchorn, Tammy M; Dowidar, Nabil; Dejong, Cornelis H C; Waddell, Ian D; Garden, O James; Ross, James A

2005-10-01

A novel proteoglycan, proteolysis inducing factor (PIF), is capable of inducing muscle proteolysis during the process of cancer cachexia, and of inducing an acute phase response in human hepatocytes. We investigated whether PIF is able to activate pro-inflammatory pathways in human Kupffer cells, the resident macrophages of the liver, and in monocytes, resulting in the production of pro-inflammatory cytokines. Normal liver tissue was obtained from patients undergoing partial hepatectomy and Kupffer cells were isolated. Monocytes were isolated from peripheral blood. Following exposure to native PIF, pro-inflammatory cytokine production from Kupffer cells and monocytes was measured and the NF-kappaB and STAT3 transcriptional pathways were investigated using electrophoretic mobility shift assays. We demonstrate that PIF is able to activate the transcription factor NF-kappaB and NF-kappaB-inducible genes in human Kupffer cells, and in monocytes, resulting in the production of pro-inflammatory cytokines such as TNF-alpha, IL-8 and IL-6. PIF enhances the expression of the cell surface molecules LFA-1 and CD14 on macrophages. PIF also activates the transcription factor STAT3 in Kupffer cells. The pro-inflammatory effects of PIF, mediated via NF-kappaB and STAT3, are important in macrophage behaviour and may contribute to the inflammatory pro-cachectic process in the liver.

Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

PubMed

Steel, Helen C; Theron, Annette J; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

2012-01-01

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

PubMed Central

Steel, Helen C.; Theron, Annette J.; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

2012-01-01

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance. PMID:22778497

Endogenous anti-inflammatory neuropeptides and pro-resolving lipid mediators: a new therapeutic approach for immune disorders

PubMed Central

Anderson, Per; Delgado, Mario

2008-01-01

Identification of the factors that regulate the immune tolerance and control the appearance of exacerbated inflammatory conditions is crucial for the development of new therapies of inflammatory and autoimmune diseases. Although much is known about the molecular basis of initiating signals and pro-inflammatory chemical mediators in inflammation, it has only recently become apparent that endogenous stop signals are critical at early checkpoints within the temporal events of inflammation. Some neuropeptides and lipid mediators that are produced during the ongoing inflammatory response have emerged as endogenous anti-inflammatory agents that participate in the regulation of the processes that ensure self-tolerance and/or inflammation resolution. Here we examine the latest research findings, which indicate that neuropeptides participate in maintaining immune tolerance in two distinct ways: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T-cell effectors. On the other hand, we also focus on lipid mediators biosynthesized from ω-3 and ω-6 polyunsaturated fatty-acids in inflammatory exudates that promote the resolution phase of acute inflammation by regulating leucocyte influx to and efflux from local inflamed sites. Both anti-inflammatory neuropeptides and pro-resolving lipid mediators have shown therapeutic potential for a variety of inflammatory and autoimmune disorders and could be used as biotemplates for the development of novel pharmacologic agents. PMID:18554314

Blowing Hot and Cold: Protecting Against Climatic Extremes (Souffler le chaud et le froid: comment se proteger contre les conditions climstiques extremes)

DTIC Science & Technology

2002-04-01

hereditary abundance, allergy and frequent airways acute inflammatory diseases in anamnesis and have been made routine clinical examination. 23-3 During...have in anamnesis (during last 2 year) 3-4 times and over acute airway inflammatory diseases: 17 persons (31,5%). 19 persons (36%) from both

In vivo antinociceptive and anti-inflammatory activities of dried and fermented processed virgin coconut oil.

PubMed

Zakaria, Z A; Somchit, M N; Mat Jais, A M; Teh, L K; Salleh, M Z; Long, K

2011-01-01

The present study was carried out to investigate the antinociceptive and anti-inflammatory activities of virgin coconut oil (VCO) produced by the Malaysian Agriculture Research and Development Institute (MARDI) using various in vivo models. Two types of VCOs, produced via standard drying (VCOA) and fermentation (VCOB) processes were used in this study. Both VCOA and VCOB were serially diluted using 1% Tween 80 to concentrations (v/v) of 10, 50 and 100%. Antinociceptive and anti- inflammatory activities of both VCOs were examined using various in vivo model systems. The antinociceptive activity of the VCOs were compared to those of 1% Tween 80 (used as a negative control), morphine (5 mg/kg) and/or acetylsalicylic acid (100 mg/kg). Both VCOA and VCOB exhibited significant (p < 0.05) dose-dependent antinociceptive activity in the acetic acid-induced writhing test. Both VCOs also exerted significant (p < 0.05) antinociceptive activity in both phases of the formalin and hot-plate tests. Interestingly, the VCOs exhibited anti-inflammatory activity in an acute (carrageenan-induced paw edema test), but not in a chronic (cotton-pellet-induced granuloma test) model of inflammation. The MARDI-produced VCOs possessed antinociceptive and anti-inflammatory activities. Further studies are needed to confirm these observations. Copyright © 2011 S. Karger AG, Basel.

High-intensity interval training induces a modest systemic inflammatory response in active, young men

PubMed Central

Zwetsloot, Kevin A; John, Casey S; Lawrence, Marcus M; Battista, Rebecca A; Shanely, R Andrew

2014-01-01

The purpose of this study was to determine: 1) the extent to which an acute session of high-intensity interval training (HIIT) increases systemic inflammatory cytokines and chemokines, and 2) whether 2 weeks of HIIT training alters the inflammatory response. Eight recreationally active males (aged 22±2 years) performed 2 weeks of HIIT on a cycle ergometer (six HIIT sessions at 8–12 intervals; 60-second intervals, 75-second active rest) at a power output equivalent to 100% of their predetermined peak oxygen uptake (VO2max). Serum samples were collected during the first and sixth HIIT sessions at rest and immediately, 15, 30, and 45 minutes post-exercise. An acute session of HIIT induced significant increases in interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α, and monocyte chemotactic protein-1 compared with rest. The concentrations of interferon-γ, granulocyte macrophage-colony-stimulating factor, and IL-1β were unaltered with an acute session of HIIT Two weeks of training did not alter the inflammatory response to an acute bout of HIIT exercise. Maximal power achieved during a VO2max test significantly increased 4.6%, despite no improvements in VO2max after 2 weeks of HIIT. These data suggest that HIIT exercise induces a small inflammatory response in young, recreationally active men; however, 2 weeks of HIIT does not alter this response. PMID:24520199

S100A8 promotes migration and infiltration of inflammatory cells in acute anterior uveitis

PubMed Central

Wang, Yuqin; Zhang, Zuhui; Zhang, Laihe; Li, Xinxin; Lu, Rui; Xu, Peipei; Zhang, Xuhong; Dai, Mali; Dai, Xiaodan; Qu, Jia; Lu, Fan; Chi, Zailong

2016-01-01

Uveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. S100A8 is a calcium-binding protein which mainly expresses in granulocytes and monocytes and plays a prominent role in the regulation of inflammatory processes and immune response. Here, we determined the role of S100A8-positive cells in acute anterior uveitis (AAU) and keratitis. In rat models of endotoxin (lipopolisaccharide, LPS) -induced uveitis (EIU) and keratitis, S100A8-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Interestingly, Glucocorticoids slightly increased S100A8 levels in leukocytes, but reduced its presence significantly in the iris-ciliary body after LPS injection. Moreover, inhibition of NF-kB activation remarkably suppressed both progression of AAU and total S100A8 levels in leukocytes and the iris-ciliary body after LPS administration. Additionally, S100A8 protein level was also found to be elevated in the serum of AAU patients parallel with the progression of AAU through the designated clinical stages. Thus, S100A8 plays a pivotal role in the processes of AAU through involvement in migration and infiltration of S100A8-positive cells. Our findings suggest that serum levels of S100A8 protein can be used to monitor inflammatory activity in AAU. PMID:27786310

S100A8 promotes migration and infiltration of inflammatory cells in acute anterior uveitis.

PubMed

Wang, Yuqin; Zhang, Zuhui; Zhang, Laihe; Li, Xinxin; Lu, Rui; Xu, Peipei; Zhang, Xuhong; Dai, Mali; Dai, Xiaodan; Qu, Jia; Lu, Fan; Chi, Zailong

2016-10-27

Uveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. S100A8 is a calcium-binding protein which mainly expresses in granulocytes and monocytes and plays a prominent role in the regulation of inflammatory processes and immune response. Here, we determined the role of S100A8-positive cells in acute anterior uveitis (AAU) and keratitis. In rat models of endotoxin (lipopolisaccharide, LPS) -induced uveitis (EIU) and keratitis, S100A8-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Interestingly, Glucocorticoids slightly increased S100A8 levels in leukocytes, but reduced its presence significantly in the iris-ciliary body after LPS injection. Moreover, inhibition of NF-kB activation remarkably suppressed both progression of AAU and total S100A8 levels in leukocytes and the iris-ciliary body after LPS administration. Additionally, S100A8 protein level was also found to be elevated in the serum of AAU patients parallel with the progression of AAU through the designated clinical stages. Thus, S100A8 plays a pivotal role in the processes of AAU through involvement in migration and infiltration of S100A8-positive cells. Our findings suggest that serum levels of S100A8 protein can be used to monitor inflammatory activity in AAU.

Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury

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

Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo

We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats.more » At 24 h post exposure, Cl{sub 2}-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR. Inhalation of Cl{sub 2} in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. • Treatment with corticosteroids alone is insufficient to counteract acute lung injury.« less

CHARACTERIZATION OF INFLAMMATORY GENE EXPRESSION AND GALECTIN-3 FUNCTION AFTER SPINAL CORD INJURY IN MICE

PubMed Central

Pajoohesh-Ganji, Ahdeah; Knoblach, Susan M.; Faden, Alan I.; Byrnes, Kimberly R.

2012-01-01

Inflammation has long been implicated in secondary tissue damage after spinal cord injury (SCI). Our previous studies of inflammatory gene expression in rats after SCI revealed two temporally correlated clusters: the first was expressed early after injury and the second was up-regulated later, with peak expression at 1–2 weeks and persistent up-regulation through 6 months. To further address the role of inflammation after SCI, we examined inflammatory genes in a second species, mice, through 28 days after SCI. Using anchor gene clustering analysis, we found similar expression patterns for both the acute and chronic gene clusters previously identified after rat SCI. The acute group returned to normal expression levels by 7 days post-injury. The chronic group, which included C1qB, p22phox and galectin-3, showed peak expression at 7 days and remained up-regulated through 28 days. Immunohistochemistry and western blot analysis showed that the protein expression of these genes was consistent with the mRNA expression. Further exploration of the role of one of these genes, galectin-3, suggests that galectin-3 may contribute to secondary injury. In summary, our findings extend our prior gene profiling data by demonstrating the chronic expression of a cluster of microglial associated inflammatory genes after SCI in mice. Moreover, by demonstrating that inhibition of one such factor improves recovery, the findings suggest that such chronic up-regulation of inflammatory processes may contribute to secondary tissue damage after SCI, and that there may be a broader therapeutic window for neuroprotection than generally accepted. PMID:22884909

Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

PubMed Central

Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

2015-01-01

Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis. PMID:26218284

Regulation of mitochondrial biogenesis and its intersection with inflammatory responses.

PubMed

Cherry, Anne D; Piantadosi, Claude A

2015-04-20

Mitochondria play a vital role in cellular homeostasis and are susceptible to damage from inflammatory mediators released by the host defense. Cellular recovery depends, in part, on mitochondrial quality control programs, including mitochondrial biogenesis. Early-phase inflammatory mediator proteins interact with PRRs to activate NF-κB-, MAPK-, and PKB/Akt-dependent pathways, resulting in increased expression or activity of coactivators and transcription factors (e.g., PGC-1α, NRF-1, NRF-2, and Nfe2l2) that regulate mitochondrial biogenesis. Inflammatory upregulation of NOS2-induced NO causes mitochondrial dysfunction, but NO is also a signaling molecule upregulating mitochondrial biogenesis via PGC-1α, participating in Nfe2l2-mediated antioxidant gene expression and modulating inflammation. NO and reactive oxygen species generated by the host inflammatory response induce the redox-sensitive HO-1/CO system, causing simultaneous induction of mitochondrial biogenesis and antioxidant gene expression. Recent evidence suggests that mitochondrial biogenesis and mitophagy are coupled through redox pathways; for instance, parkin, which regulates mitophagy in chronic inflammation, may also modulate mitochondrial biogenesis and is upregulated through NF-κB. Further research on parkin in acute inflammation is ongoing. This highlights certain common features of the host response to acute and chronic inflammation, but caution is warranted in extrapolating findings across inflammatory conditions. Inflammatory mitochondrial dysfunction and oxidative stress initiate further inflammatory responses through DAMP/PRR interactions and by inflammasome activation, stimulating mitophagy. A deeper understanding of mitochondrial quality control programs' impact on intracellular inflammatory signaling will improve our approach to the restoration of mitochondrial homeostasis in the resolution of acute inflammation.

Improvement of bioavailability and anti-inflammatory potential of curcumin in combination with emu oil.

PubMed

Jeengar, Manish Kumar; Shrivastava, Shweta; Nair, Kala; Singareddy, Sreenivasa Reddy; Putcha, Uday Kumar; Talluri, M V N Kumar; Naidu, V G M; Sistla, Ramakrishna

2014-12-01

The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.

Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

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

Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu

Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, andmore » chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.« less

Low level laser therapy reduces acute lung inflammation without impairing lung function.

PubMed

Cury, Vivian; de Lima, Thais Martins; Prado, Carla Maximo; Pinheiro, Nathalia; Ariga, Suely K K; Barbeiro, Denise F; Moretti, Ana I; Souza, Heraldo P

2016-12-01

Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm 2 . Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-α, IL-1β, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

Code of Federal Regulations, 2014 CFR

2014-01-01

...), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders (farcy), acute... poisoning), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders... osteoporosis. (13) Glanders (farcy). (14) Acute inflammatory lameness. (15) Extensive fistula. (b) Carcasses of...

9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

Code of Federal Regulations, 2012 CFR

2012-01-01

...), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders (farcy), acute... poisoning), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders... osteoporosis. (13) Glanders (farcy). (14) Acute inflammatory lameness. (15) Extensive fistula. (b) Carcasses of...

9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

Code of Federal Regulations, 2010 CFR

2010-01-01

...), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders (farcy), acute... poisoning), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders... osteoporosis. (13) Glanders (farcy). (14) Acute inflammatory lameness. (15) Extensive fistula. (b) Carcasses of...

9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

Code of Federal Regulations, 2013 CFR

2013-01-01

...), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders (farcy), acute... poisoning), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders... osteoporosis. (13) Glanders (farcy). (14) Acute inflammatory lameness. (15) Extensive fistula. (b) Carcasses of...

9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

Code of Federal Regulations, 2011 CFR

2011-01-01

...), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders (farcy), acute... poisoning), infectious anemia (swamp fever), dourine, acute influenza, generalized osteoporosis, glanders... osteoporosis. (13) Glanders (farcy). (14) Acute inflammatory lameness. (15) Extensive fistula. (b) Carcasses of...

Class II obese and healthy pregnant controls exhibit indistinguishable pro‐ and anti‐inflammatory immune responses to Caesarian section

PubMed Central

Graham, Caroline; Thorleifson, Mullein; Stefura, William P.; Funk, Duane J.

2017-01-01

Abstract Introduction Obesity during pregnancy is associated with meta‐inflammation and an increased likelihood of clinical complications. Surgery results in intense, acute inflammatory responses in any individual. Because obese individuals exhibit constitutive inflammatory responses and high rates of Caesarian section, it is important to understand the impact of surgery in such populations. Whether more pronounced pro‐inflammatory cytokine responses and/or counterbalancing changes in anti‐inflammatory immune modulators occurs is unknown. Here we investigated innate immune capacity in vivo and in vitro in non‐obese, term‐pregnant controls versus healthy, term‐pregnant obese women (Class II, BMI 35–40). Methods Systemic in vivo induction of eleven pro‐ and anti‐inflammatory biomarkers and acute phase proteins was assessed in plasma immediately prior to and again following Caesarian section surgery. Independently, innate immune capacity was examined by stimulating freshly isolated PBMC in vitro with a panel of defined PRR‐ligands for TLR4, TLR8, TLR3, and RLR 24 h post‐surgery. Results The kinetics and magnitude of the in vivo inflammatory responses examined were indistinguishable in the two populations across the broad range of biomarkers examined, despite the fact that obese women had higher baseline inflammatory status. Deliberate in vitro stimulation with a range of PRR ligands also elicited pro‐ and anti‐inflammatory cytokine responses that were indistinguishable between control and obese mothers. Conclusions Acute in vivo innate immune responses to C‐section, as well as subsequent in vitro stimulation with a panel of microbial mimics, are not detectably altered in Class II obese women. The data argue that while Class II obesity is undesirable, it has minimal impact on the in vivo inflammatory response, or innate immunomodulatory capacity, in women selecting C‐section. PMID:28544689

Cardioprotective effect of vitamin D2 on isoproterenol-induced myocardial infarction in diabetic rats.

PubMed

El Agaty, Sahar M

2018-03-08

To assess the effect of vitamin D 2 and to elucidate the underlying mechanisms on acute myocardial injury induced by isoproterenol (ISO) in diabetic rats. Rats were divided into control rats, diabetic rats (DM), diabetic rats received ISO (DM-ISO), and diabetic rats pretreated with vitamin D 2 and received ISO (DM-D 2 -ISO). Vitamin D 2 pretreatment significantly decreased fasting glucose and myocardial malondialdehyde, associated with increased insulin, myocardial glutathione and superoxide dismutase in DM-D 2 -ISO versus DM-ISO. The serum triglycerides, total cholesterol, and LDL were significantly decreased, along with increased HDL and adiponectin. Poly-ADP ribose polymerase, cyclooxygenase-2, tumour necrosis factor alpha, interleukin-6, caspase-3, BAX, and p53 were significantly downregulated in myocardium of DM-D 2 -ISO versus DM-ISO. Histological studies showed diminished inflammatory cells infiltration in myocardium of DM-D 2 -ISO versus DM-ISO. Vitamin D 2 ameliorates hyperglycaemia, dyslipidaemia, redox imbalance, inflammatory and apoptotic processes, protecting the myocardium of diabetic rats against acute myocardial infarction.

Inflammation, Fracture and Bone Repair

PubMed Central

Loi, Florence; Córdova, Luis A.; Pajarinen, Jukka; Lin, Tzu-hua; Yao, Zhenyu; Goodman, Stuart B.

2016-01-01

The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair. PMID:26946132

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

PubMed Central

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

2016-01-01

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

Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

PubMed

Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

2009-11-14

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the severity of acute pancreatitis.

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

PubMed

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

2016-03-01

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

Fever of unknown origin in the elderly.

PubMed

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

1989-06-01

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

Changes in Gene Expression and Metabolism in the Testes of the Rat following Spinal Cord Injury

PubMed Central

Fortune, Ryan D.; Grill, Raymond J.; Beeton, Christine; Tanner, Mark; Huq, Redwan

2017-01-01

Abstract Spinal cord injury (SCI) results in devastating changes to almost all aspects of a patient's life. In addition to a permanent loss of sensory and motor function, males also will frequently exhibit a profound loss of fertility through poorly understood mechanisms. We demonstrate that SCI causes measureable pathology in the testis both acutely (24 h) and chronically up to 1.5 years post-injury, leading to loss in sperm motility and viability. SCI has been shown in humans and rats to induce leukocytospermia, with the presence of inflammatory cytokines, anti-sperm antibodies, and reactive oxygen species found within the ejaculate. Using messenger RNA and metabolomic assessments, we describe molecular and cellular changes that occur within the testis of adult rats over an acute to chronic time period. From 24 h, 72 h, 28 days, and 90 days post-SCI, the testis reveal a distinct time course of pathological events. The testis show an acute drop in normal sexual organ processes, including testosterone production, and establishment of a pro-inflammatory environment. This is followed by a subacute initiation of an innate immune response and loss of cell cycle regulation, possibly due to apoptosis within the seminiferous tubules. At 1.5 years post-SCI, there is a chronic low level immune response as evidenced by an elevation in T cells. These data suggest that SCI elicits a wide range of pathological processes within the testes, the actions of which are not restricted to the acute phase of injury but rather extend chronically, potentially through the lifetime of the subject. The multiplicity of these pathological events suggest a single therapeutic intervention is unlikely to be successful. PMID:27750479

Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis.

PubMed

Scorza, Carla A; Marques, Marcia J G; Gomes da Silva, Sérgio; Naffah-Mazzacoratti, Maria da Graça; Scorza, Fulvio A; Cavalheiro, Esper A

2018-03-06

Mesial temporal lobe epilepsy is a serious brain disorder in adults that is often preceded by an initial brain insult, such as status epilepticus (SE), that after a latent period leads to recurrent seizures. Post-SE models are widely used for studies on epileptogenic processes. Previous findings of our laboratory suggested that the Neotropical rodents Proechimys exhibit endogenous antiepileptogenic mechanisms in post-SE models. Strong body of research supports that SE triggers a rapid and dramatic upregulation of inflammatory mediators and vascular endothelial growth factor (VEGF). In this work we found that, in the epilepsy-resistant Proechimys, hippocampal and cortical levels of inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α) and VEGF remained unchanged 24h after SE, strongly contrasting to the high levels of post-SE changes observed in Wistar rats. Furthermore, substantial differences in the brain baseline levels of these proteins were encountered between animal species studied. Since inflammatory cytokines and VEGF have been recognized as major orchestrators of the epileptogenic process, our results suggest their role in the antiepileptogenic mechanisms previously described in Proechimys. Copyright © 2017 Elsevier B.V. All rights reserved.

Design, synthesis, and structure–activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury

PubMed Central

Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

2018-01-01

Purpose The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. Methods A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Results Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f, was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. Conclusion The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury. PMID:29719375

Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

PubMed

Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

2014-02-05

The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production. Copyright © 2013 Elsevier B.V. All rights reserved.

Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis

PubMed Central

2014-01-01

Introduction Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee. Methods Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid. Results Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues. Conclusion These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA. PMID:24964765

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis

PubMed Central

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-01-01

BACKGROUND AND PURPOSE Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. EXPERIMENTAL APPROACH Rats were given CER (80 µg·kg−1 for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg−1 i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B4 and prostaglandin (PG)E2; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. KEY RESULTS Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B4 and prostaglandin E2 levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. CONCLUSIONS AND IMPLICATIONS Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. PMID:20977452

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis.

PubMed

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-11-01

Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. Rats were given CER (80 µg·kg⁻¹ for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg⁻¹ i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B₄ and prostaglandin (PG)E₂ ; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B₄ and prostaglandin E₂ levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Appendiceal Enterobius vermicularis infestation in adults.

PubMed

Isik, Burak; Yilmaz, Mehmet; Karadag, Nese; Kahraman, Latif; Sogutlu, Gokhan; Yilmaz, Sezai; Kirimlioglu, Vedat

2007-01-01

The objective of this study is to evaluate the incidence of Enterobius vermicularis in the appendices of the adult population and a possible relationship between E. vermicularis and acute appendicitis. E. vermicularis was identified in 18 (2%) of 890 patients. Six hundred sixty-five operations were performed for presumptive diagnosis of acute appendicitis, and E. vermicularis was found in 12 (2%) patients. The histopathological examination revealed acute inflammatory cells in four cases (33%). Three of these four specimens included luminal ova and one E. vermicularis. Histopathological examination of six cases revealed E. vermicularis in 225 incidental appendectomies with no evidence of either acute or chronic inflammatory cells. This study suggests a relationship between the presence of E. vermicularis ova and acute inflammation, but the presence of the pinworm in the lumen of the appendix is coincidental. On the other hand E. vermicularis in the appendix lumen can cause symptoms of acute appendicitis.

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation

PubMed Central

Nizamutdinova, Irina Tsoy; Dusio, Giuseppina F.; Gasheva, Olga Yu.; Skoog, Hunter; Tobin, Richard; Peddaboina, Chander; Meininger, Cynthia J.; Zawieja, David C.; Newell-Rogers, M. Karen; Gashev, Anatoliy A.

2016-01-01

This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics. PMID:27875806

Histopathology of Lyme arthritis in LSH hamsters

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

Hejka, A.; Schmitz, J.L.; England, D.M.

1989-05-01

The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding wasmore » destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis.« less

Anti-inflammatory and in-vitro antibacterial activities of Traditional Chinese Medicine Formula Qingdaisan.

PubMed

Zhao, Xinghua; He, Xin; Zhong, Xiuhui

2016-12-05

Qingdaisan (Formulated Indigo powder, QDS) are widely used for treatment of aphtha, sore throat and bleeding gums in China. The aim of the study is to evaluate the anti-inflammatory, antibacterial and dental ulcer therapeutic effects of QDS. Dimethylbenzene-induced ear edema test and cotton pellet-induced granuloma test were used to evaluate anti-inflammatory activities of QDS on acute and chronic inflammatory. The healing time and local pathologic changes were used to assess the therapeutic effects of QDS on dental ulcer. The antibacterial activities of each component and the whole formulation of QDS were determined by agar well diffusion assay. High-dose and low-dose QDS were tested in this experiment and Gui Lin Watermelon Frost Powder (GLWFP) was used as positive control. Oral treatment with QDS significantly accelerated the healing of ulcerative lesions induced by phenol injury. The dental ulcers of high-dose QDS group were all healed within 6 days. It was shorter than those of low-dose QDS group and GLWFP group. Less quantity of inflammatory cells and plenty fibroblasts were observed in pathological section of QDS groups. QDS also exhibited significant anti-inflammatory activity both in acute and chronic animal models. Although some of the components exhibited antibacterial activities, the whole formulation of QDS didn't show any significant antibacterial activity in vitro. The study showed that QDS has obviously anti-inflammatory activity for both acute and chronic inflammatory, also has a remarkable effect for healing dental ulcer caused by phenol. QDS didn't have antibacterial activity to selected strains in vitro.

Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

PubMed

Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

2014-04-01

Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

Role of oxygen free radicals in patients with acute pancreatitis

PubMed Central

Park, Byung Kyu; Chung, Jae Bock; Lee, Jin Heon; Suh, Jeong Hun; Park, Seung Woo; Song, Si Young; Kim, Hyeyoung; Kim, Kyung Hwan; Kang, Jin Kyung

2003-01-01

AIM: The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis. METHODS: The plasma levels of C-reactive protein (CRP), lipid peroxide (LPO), myeloperoxidase (MPO) and superoxide dismutase (SOD) were measured in 13 patients with acute pancreatitis and 14 healthy volunteers. RESULTS: Among the patients with acute pancreatitis, there were higher plasma levels of LPO and MPO and lower SOD activity in patients with severe pancreatitis than in those with mild pancreatitis. However, there was no significant difference in the serum marker of oxidative stress no matter what the etiology was. The LPO level was especially correlated with the concentration of serum CRP and CT severity index. CONCLUSION: The oxygen free radicals may be closely associated with inflammatory process and the severity of acute pancreatitis. Especially, the concentration of plasma LPO is a meaningful index for determining the severity of the disease. PMID:14562390

State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease.

PubMed

Puri, Latika; Nottage, Kerri A; Hankins, Jane S; Anghelescu, Doralina L

2018-02-01

Acute vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD). Multiple complex pathophysiological processes can result in pain during a VOC. Despite significant improvements in the understanding and management of SCD, little progress has been made in the management of pain in SCD, although new treatments are being explored. Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of treatment of VOC pain, but new classes of drugs are being tested to prevent and treat acute pain. Advancements in the understanding of the pathophysiology of SCD and pain and the pharmacogenomics of opioids have yet to be effectively utilized in the management of VOC. Opioid tolerance and opioid-induced hyperalgesia are significant problems associated with the long-term use of opioids, and better strategies for chronic pain therapy are needed. This report reviews the mechanisms of pain associated with acute VOC, describes the current management of VOC, and describes some of the new therapies under evaluation for the management of acute VOC in SCD.

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo.

PubMed

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-09-19

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25-100 μm wide) and minibeams (200-800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a(+) thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool.

Sulfasalazine-Induced Crystalluria Causing Severe Acute Kidney Injury.

PubMed

Durando, Michael; Tiu, Hannah; Kim, James Soo

2017-12-01

Sulfasalazine is an anti-inflammatory agent commonly used in the treatment of autoimmune conditions such as inflammatory bowel disease and rheumatoid arthritis. Sulfasalazine is converted by gut bacteria into sulfapyridine and the clinically active metabolite 5-aminosalicylic acid (5-ASA), and its efficacy is proportional to the 5-ASA concentration within the intestinal lumen. Renal complications are commonly reported for the chemically similar 5-ASA derivative mesalamine, but are not well-known side effects of sulfasalazine therapy. We report a 72-year-old patient with Crohn's disease managed with sulfasalazine for more than 10 years who presented with severe acute kidney injury (serum creatinine, 9.7mg/dL). Renal ultrasound revealed calculi and he subsequently spontaneously voided innumerable stones, which were composed of sulfasalazine metabolites. His renal calculi cleared and serum creatinine concentration improved to 3.1mg/dL after discontinuing sulfasalazine therapy and intravenous fluid hydration. His kidney function eventually returned to baseline. This case demonstrates that renal complications, in particular nephrolithiasis, may be an under-reported but potentially serious phenomenon in patients with inflammatory bowel disease treated with sulfasalazine and that their hydration status may play an important role in this process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction.

PubMed

Hofmann, R; Tornvall, P; Witt, N; Alfredsson, J; Svensson, L; Jonasson, L; Nilsson, L

2018-04-01

Oxygen therapy has been used routinely in normoxemic patients with suspected acute myocardial infarction (AMI) despite limited evidence supporting a beneficial effect. AMI is associated with a systemic inflammation. Here, we hypothesized that the inflammatory response to AMI is potentiated by oxygen therapy. The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) multicentre trial randomized patients with suspected AMI to receive oxygen at 6 L min -1 for 6-12 h or ambient air. For this prespecified subgroup analysis, we recruited patients with confirmed AMI from two sites for evaluation of inflammatory biomarkers at randomization and 5-7 h later. Ninety-two inflammatory biomarkers were analysed using proximity extension assay technology, to evaluate the effect of oxygen on the systemic inflammatory response to AMI. Plasma from 144 AMI patients was analysed whereof 76 (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a significant increase, whereas 13 were decreased 5-7 h after randomization. The inflammatory response did not differ between the two treatment groups neither did plasma troponin T levels. After adjustment for increase in troponin T over time, age and sex, the release of inflammation-related biomarkers was still similar in the groups. In a randomized controlled setting of normoxemic patients with AMI, the use of supplemental oxygen did not have any significant impact on the early release of systemic inflammatory markers. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Lymphatic dysregulation in intestinal inflammation: new insights into inflammatory bowel disease pathomechanisms.

PubMed

Becker, F; Yi, P; Al-Kofahi, M; Ganta, V C; Morris, J; Alexander, J S

2014-03-01

Alterations in the intestinal lymphatic network are well-established features of human and experimental inflammatory bowel disease (IBD). Such lymphangiogenic expansion might enhance classic intestinal lymphatic transport, eliminating excess accumulations of fluid, inflammatory cells and mediators, and could therefore be interpreted as an 'adaptive' response to acute and chronic inflammatory processes. However, whether these new lymphatic vessels are functional, unregulated or immature (and what factors may promote 'maturation' of these vessels) is currently an area under intense investigation. It is still controversial whether impaired lymphatic function in IBD is a direct consequence of the intestinal inflammation, or a preceding lymphangitis-like event. Current research has uncovered novel regulatory factors as well as new roles for familiar signaling pathways, which appear to be linked to inflammation-induced lymphatic alterations. The current review summarizes mechanisms amplifying lymphatic dysregulation and remodeling in intestinal inflammation at the organ, cell and molecular levels and discusses the influence of lymphangiogenesis and intestinal lymphatic transport function as they relate to IBD pathophysiology.

[Etiology of acute and chronic pyelonephritis in children in Khabarovsk region].

PubMed

Kozlova, E A; Kholodok, G N; Alekseeva, I N; Kozlov, V K

2008-01-01

Microflora of urinary tract was studied in 419 children aged 1 - 17 years and hospitalized due to acute or chronic pyelonephritis. Etiology of inflammatory process was established in 57.8% of cases. According to our study, etiologic structure of causative agents of pyelonephritis did not differ from all-Russian data. The leading positions belonged to Gram-negative microorganisms from Enterobacteriaceae family: Escherichia coli, Proteus mirabilis, and Klebsiella spp. Results of the study point to high susceptibility of main causative agents of pyelonephritis to cephalosporins, aminoglycosides, and fluoroquinolones. High resistance to aminopenicillines was noted. In several isolates from Enterobacteriaceae family significant resistance to nalidixic acid and furazidin was observed.

Medic - Abdominal Pain: A Decision Support Program for the Management of Acute Abdominal Pain. (User’s Manual)

DTIC Science & Technology

1989-10-11

presence of diverticular disease does not preclude development of acute appendicitis concxitantly. The initial medical treatment is the same as for...appendicitis see APPENDICITIS. c. Pelvic inflammatory disease see PID. d. Diverticulitis most commonly involves the descending (left) colon . Symptoms...Five additional categories are included for female patients. These are: pelvic inflammatory disease (PID), urinary tract infection (UTI), ovarian cyst

Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics

PubMed Central

Minkwitz, Susann; Schmock, Aysha; Bormann, Nicole; Kurtoglu, Alper; Tsitsilonis, Serafeim; Manegold, Sebastian

2018-01-01

Reasons for the development of chronic tendon pathologies are still under debate and more basic knowledge is needed about the different diseases. The aim of the present study was therefore to characterize different acute and chronic Achilles tendon disorders. Achilles tendon samples from patients with chronic tendinopathy (n = 7), chronic ruptures (n = 6), acute ruptures (n = 13), and intact tendons (n = 4) were analyzed. The histological score investigating pathological changes was significantly increased in tendinopathy and chronic ruptures compared to acute ruptures. Inflammatory infiltration was detected by immunohistochemistry in all tendon pathology groups, but was significantly lower in tendinopathy compared to chronic ruptures. Quantitative real-time PCR (qRT-PCR) analysis revealed significantly altered expression of genes related to collagens and matrix modeling/remodeling (matrix metalloproteinases, tissue inhibitors of metalloproteinases) in tendinopathy and chronic ruptures compared to intact tendons and/or acute ruptures. In all three tendon pathology groups markers of inflammation (interleukin (IL) 1β, tumor necrosis factor α, IL6, IL10, IL33, soluble ST2, transforming growth factor β1, cyclooxygenase 2), inflammatory cells (cluster of differentaition (CD) 3, CD68, CD80, CD206), fat metabolism (fatty acid binding protein 4, peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, adiponectin), and innervation (protein gene product 9.5, growth associated protein 43, macrophage migration inhibitory factor) were detectable, but only in acute ruptures significantly regulated compared to intact tendons. The study gives an insight into structural and molecular changes of pathological processes in tendons and might be used to identify targets for future therapy of tendon pathologies. PMID:29385715

The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review

PubMed Central

Famakin, Bolanle M.

2014-01-01

It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to recruitment of inflammatory cells and the production of more inflammatory mediators that result in activation of the adaptive immune response. Under ideal conditions, this inflammation gives way to tissue repair and attempts at regeneration. However, for reasons that are just being understood, immunosuppression occurs following acute stroke leading to post-stroke immunodepression. This review focuses on the current state of knowledge regarding innate and adaptive immune activation in response to focal cerebral ischemia as well as the immunodepression that can occur following stroke. A better understanding of the intricate and complex events that take place following immune response activation, to acute cerebral ischemia, is imperative for the development of effective novel immunomodulatory therapies for the treatment of acute stroke. PMID:25276490

Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

PubMed Central

Thom, Vivien; Arumugam, Thiruma V.; Magnus, Tim; Gelderblom, Mathias

2017-01-01

Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg. PMID:28824617

Treating acute cystitis with biodegradable micelle-encapsulated quercetin

PubMed Central

Wang, Bi Lan; Gao, Xiang; Men, Ke; Qiu, Jinfeng; Yang, Bowen; Gou, Ma Ling; Huang, Mei Juan; Huang, Ning; Qian, Zhi Yong; Zhao, Xia; Wei, Yu Quan

2012-01-01

Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy. PMID:22661886

Sex Differences in the Association between Stressor-Evoked Interleukin-6 Reactivity and C-Reactive Protein

PubMed Central

Lockwood, Kimberly G.; Marsland, Anna L.; Cohen, Sheldon; Gianaros, Peter J.

2016-01-01

Individuals differ consistently in the magnitude of their inflammatory responses to acute stressors, with females often showing larger responses than males. While the clinical significance of these individual differences remains unclear, it may be that greater inflammatory responses relate to increased systemic inflammation and thereby risk for chronic inflammatory disease. Here, we examined whether acute stressor-evoked interleukin (IL)-6 responses associate with resting levels of C-reactive protein (CRP), a marker of systemic inflammation, and whether this association differs by sex. Subjects were 57 healthy midlife adults (30–51 years; 33% female; 68% white). Blood was drawn before and 30-min after two mental stress tasks: a multisource interference task and a Stroop color word task. Hierarchical regressions controlling for age, sex, race, and BMI tested whether stressor-evoked IL-6 responses were associated with resting CRP and whether this association differed by sex. Results indicated that sex and stressor-evoked IL-6 responses interacted to predict CRP (ΔR2 = .08, B = −1.33, β = −.39, p = .02). In males, larger stressor-evoked IL-6 responses associated with higher CRP, whereas in females, stressor-evoked IL-6 responses showed a non-significant negative association with CRP. These findings indicate that inflammatory responses to acute stressors associate with resting levels of CRP; however, this association differs by sex. Previous literature suggests that there are sex differences in stressor-evoked IL-6 responses, but this is the first study to show sex differences in the relationship between acute inflammatory responses and systemic inflammation. The contribution of these sex differences to inflammatory disease risk warrants further investigation. PMID:27377561

Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

PubMed

Wandji, Bibiane Aimée; Bomba, Francis Desire Tatsinkou; Nkeng-Efouet, Pepin Alango; Piegang, Basile Nganmegne; Kamanyi, Albert; Nguelefack, Télesphore Benoît

2018-02-01

Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

Topical anti-inflammatory potential of Physalin E from Physalis angulata on experimental dermatitis in mice.

PubMed

Pinto, N B; Morais, T C; Carvalho, K M B; Silva, C R; Andrade, G M; Brito, G A C; Veras, M L; Pessoa, O D L; Rao, V S; Santos, F A

2010-08-01

The anti-inflammatory effect of physalin E, a seco-steroid isolated from Physalis angulata L. was evaluated on acute and chronic models of dermatitis induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and oxazolone, respectively, in mouse ear. The changes in ear edema/thickness, production of pro-inflammatory cytokines (TNF-alpha and IFN-gamma), myeloperoxidase (MPO) activity, and histological and immunohistochemical findings were analysed, as indicators of dermal inflammation. Similar to dexamethasone, topically applied Physalin E (0.125; 0.25 and 0.5 mg/ear) potently inhibited the TPA and oxazolone-induced dermatitis, leading to substantial reductions in ear edema/thickness, pro-inflammatory cytokines, and MPO activity. These effects were reversed by mifepristone, a steroid antagonist and confirmed by immunohistochemical and histopathological analysis. The data suggest that physalin E may be a potent and topically effective anti-inflammatory agent useful to treat the acute and chronic skin inflammatory conditions. 2010 Elsevier GmbH. All rights reserved.

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

Translation control: a multifaceted regulator of inflammatory response.

PubMed

Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen

2010-04-01

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, toxic shock, 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.

Antibiotics versus appendectomy in the management of acute appendicitis: a review of the current evidence

PubMed Central

Fitzmaurice, Gerard J.; McWilliams, Billy; Hurreiz, Hisham; Epanomeritakis, Emanuel

2011-01-01

Background Acute appendicitis remains the most common cause of the acute abdomen in young adults, and the mainstay of treatment in most centres is an appendectomy. However, treatment for other intra-abdominal inflammatory processes, such as diverticulitis, consists initially of conservative management with antibiotics. The aim of this study was to determine the role of antibiotics in the management of acute appendicitis and to assess if appendectomy remains the gold standard of care. Methods A literature search using MEDLINE and the Cochrane Library identified studies published between 1999 and 2009, and we reviewed all relevant articles. The articles were critiqued using the Public Health Resource Unit (2006) appraisal tools. Results Our search yielded 41 papers, and we identified a total of 13 papers within the criteria specified. All of these papers, while posing pertinent questions and demonstrating the role of antibiotics as a bridge to surgery, failed to adequately justify their findings that antibiotics could be used as a definitive treatment of acute appendicitis. Conclusion Appendectomy remains the gold standard of treatment for acute appendicitis based on the current evidence. PMID:21651835

Antibiotics versus appendectomy in the management of acute appendicitis: a review of the current evidence.

PubMed

Fitzmaurice, Gerard J; McWilliams, Billy; Hurreiz, Hisham; Epanomeritakis, Emanuel

2011-10-01

Acute appendicitis remains the most common cause of the acute abdomen in young adults, and the mainstay of treatment in most centres is an appendectomy. However, treatment for other intra-abdominal inflammatory processes, such as diverticulitis, consists initially of conservative management with antibiotics. The aim of this study was to determine the role of antibiotics in the management of acute appendicitis and to assess if appendectomy remains the gold standard of care. A literature search using MEDLINE and the Cochrane Library identified studies published between 1999 and 2009, and we reviewed all relevant articles. The articles were critiqued using the Public Health Resource Unit (2006) appraisal tools. Our search yielded 41 papers, and we identified a total of 13 papers within the criteria specified. All of these papers, while posing pertinent questions and demonstrating the role of antibiotics as a bridge to surgery, failed to adequately justify their findings that antibiotics could be used as a definitive treatment of acute appendicitis. Appendectomy remains the gold standard of treatment for acute appendicitis based on the current evidence.

Paradoxical effects of vitamin C in Chagas disease.

PubMed

Castanheira, J R P T; Castanho, R E P; Rocha, H; Pagliari, C; Duarte, M I S; Therezo, A L S; Chagas, E F B; Martins, L P A

2018-05-05

Trypanosoma cruzi infection stimulates inflammatory mediators which cause oxidative stress, and the use of antioxidants can minimize the sequelae of Chagas disease. In order to evaluate the efficacy of vitamin C in minimizing oxidative damage in Chagas disease, we orally administered ascorbic acid to Swiss mice infected with 5.0 × 10 4 trypomastigote forms of T. cruzi QM2 strain. These animals were treated for 60 days to investigate the acute phase and 180 days for the chronic phase. During the acute phase, the animals in the infected and treated groups demonstrated lower parasitemia and inflammatory processes were seen in more mice in these groups, probably due to the higher concentration of nitric oxide, which led to the formation of peroxynitrite. The decrease in reduced glutathione concentration in this group showed a circulating oxidant state, and this antioxidant was used to regenerate vitamin C. During the chronic phase, the animals in the infected and treated group showed a decrease in ferric reducing ability of plasma and uric acid concentrations as well as mobilization of bilirubin (which had higher plasma concentration), demonstrating cooperation between endogenous non-enzymatic antioxidants to combat increased oxidative stress. However, lower ferrous oxidation in xylenol orange concentrations was found in the infected and treated group, suggesting that vitamin C provided biological protection by clearing the peroxynitrite, attenuating the chronic inflammatory process in the tissues and favoring greater survival in these animals. Complex interactions were observed between the antioxidant systems of the host and parasite, with paradoxical actions of vitamin C. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of phonophoresis with Arnica montana onto acute inflammatory process in rat skeletal muscles: an experimental study.

PubMed

Alfredo, Patrícia P; Anaruma, Carlos A; Pião, Antônio C S; João, Silvia M A; Casarotto, Raquel A

2009-05-01

This study aimed at verifying the effects of phonophoresis associated with Arnica montana on the acute phase of an inflammatory muscle lesion. Forty Wistar male rats (300+/-50 g), of which the Tibialis Anterior muscle was surgically lesioned, were divided into four groups (n=10 each): control group received no treatment; the ultrasound group (US) was treated in pulsed mode with 1-MHz frequency, 0.5 W/cm(2) intensity (spatial and temporal average - SATA), duty cycle of 1:2 (2 ms on, 4 ms off, 50%), time of application 3 min per session, one session per day, for 3 days; the phonophoresis or ultrasound plus arnica (US+A) group was treated with arnica with the same US parameters plus arnica gel; and the arnica group (A) was submitted to massage with arnica gel, also for 3 min, once a day, for 3 days. Treatment started 24h after the surgical lesion. On the 4th day after lesion creation, animals were sacrificed and sections of the lesioned, inflamed muscle were removed for quantitative (mononuclear and polymorphonuclear cell count) and qualitative histological analysis. Collected data from the 4 groups were statistically analyzed and the significance level set at p<0.05. Results show higher mononuclear cell density in all three treated groups with no significant difference between them, but values were significantly different (p<0.0001) when compared to control group's. As to polymorphonuclear cell density, significant differences were found between control group (p=0.0134) and US, US+A and A groups; the arnica group presented lesser density of polymorphonuclear cells when compared (p=0.0134) to the other groups. No significant difference was found between US and US+A groups. While the massage with arnica gel proved to be an effective anti-inflammatory on acute muscle lesion in topic use, these results point to ineffectiveness of Arnica montana phonophoresis, US having seemingly checked or minimized its anti-inflammatory effect.

High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia.

PubMed

Nishimon, Shohei; Ohnuma, Tohru; Takebayashi, Yuto; Katsuta, Narimasa; Takeda, Mayu; Nakamura, Toru; Sannohe, Takahiro; Higashiyama, Ryoko; Kimoto, Ayako; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-Ichi; Tomino, Yasuhiko; Arai, Heii

2017-06-02

Inflammation may be involved in the pathophysiology of schizophrenia. However, few cross-sectional or longitudinal studies have examined changes in biomarker expression to evaluate diagnostic and prognostic efficacy in acute-stage schizophrenia. We compared serum inflammatory biomarker concentrations in 87 patients with acute-stage schizophrenia on admission to 105 age-, sex-, and body mass index (BMI)-matched healthy controls. The measured biomarkers were soluble tumor necrosis factor receptor 1 (sTNFR1) and adiponectin, which are associated with inflammatory responses, and pigment epithelium-derived factor (PEDF), which has anti-inflammatory properties. We then investigated biomarker concentrations and associations with clinical factors in 213 patients (including 42 medication-free patients) and 110 unmatched healthy controls to model conditions typical of clinical practice. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale and Global Assessment of Function. In 121 patients, biomarker levels and clinical status were evaluated at both admission and discharge. Serum sTNFR1 was significantly higher in patients with acute-stage schizophrenia compared to matched controls while no significant group differences were observed for the other markers. Serum sTNFR1 was also significantly higher in the 213 patients compared to unmatched controls. The 42 unmedicated patients had significantly lower PEDF levels compared to controls. Between admission and discharge, sTNFR1 levels decreased significantly; however, biomarker changes did not correlate with clinical symptoms. The discriminant accuracy of sTNFR1 was 93.2% between controls and patients, showing no symptom improvement during care. Inflammation and a low-level anti-inflammatory state may be involved in both schizophrenia pathogenesis and acute-stage onset. High serum sTNFR1 in the acute stage could be a useful prognostic biomarker for treatment response in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

UP-REGULATION OF IL-6, IL-8 AND CCL2 GENE EXPRESSION AFTER ACUTE INFLAMMATION: CORRELATION TO CLINICAL PAIN

PubMed Central

Wang, Xiao-Min; Hamza, May; Wu, Tai-Xia; Dionne, Raymond A.

2012-01-01

Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery clinical model of acute inflammation. Tissue injury resulted in a significant up-regulation in the gene expression of Interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). The up-regulation of IL-6 gene expression was significantly correlated to the up-regulation on the gene expression of IL-8, CCL2, CXCL1 and CXCL2. Interestingly, the tissue injury induced up-regulation of IL-6 gene expression, IL-8 and CCL2 were positively correlated to pain intensity at 3 hours post-surgery, the onset of acute inflammatory pain. However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that up-regulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect for ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs. PMID:19233564

Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure.

PubMed

Lal, Bikrant B; Alam, Seema; Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev

2018-01-11

There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury. A total of 84 children with acute-on-chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute-on-chronic liver failure. The median duration from acute-on-chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation. Acute kidney injury developed in 22.6% of children with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and presence of systemic inflammatory response syndrome were high risk factors for acute kidney injury. Development of acute kidney injury in a child with acute-on-chronic liver failure suggests poor outcome and need for early intervention. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neutrophils: Beneficial and Harmful Cells in Septic Arthritis

PubMed Central

Boff, Daiane; Crijns, Helena; Teixeira, Mauro M.

2018-01-01

Septic arthritis is an inflammatory joint disease that is induced by pathogens such as Staphylococcus aureus. Infection of the joint triggers an acute inflammatory response directed by inflammatory mediators including microbial danger signals and cytokines and is accompanied by an influx of leukocytes. The recruitment of these inflammatory cells depends on gradients of chemoattractants including formylated peptides from the infectious agent or dying cells, host-derived leukotrienes, complement proteins and chemokines. Neutrophils are of major importance and play a dual role in the pathogenesis of septic arthritis. On the one hand, these leukocytes are indispensable in the first-line defense to kill invading pathogens in the early stage of disease. However, on the other hand, neutrophils act as mediators of tissue destruction. Since the elimination of inflammatory neutrophils from the site of inflammation is a prerequisite for resolution of the acute inflammatory response, the prolonged stay of these leukocytes at the inflammatory site can lead to irreversible damage to the infected joint, which is known as an important complication in septic arthritis patients. Thus, timely reduction of the recruitment of inflammatory neutrophils to infected joints may be an efficient therapy to reduce tissue damage in septic arthritis. PMID:29401737

Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation.

PubMed

Kanzawa, Noriyuki; Nishigaki, Kazuo; Hayashi, Takaya; Ishii, Yuichi; Furukawa, Souichi; Niiro, Ayako; Yasui, Fumihiko; Kohara, Michinori; Morita, Kouichi; Matsushima, Kouji; Le, Mai Quynh; Masuda, Takao; Kannagi, Mari

2006-12-22

Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.

Microalgae-derived oxylipins decrease inflammatory mediators by regulating the subcellular location of NFκB and PPAR-γ.

PubMed

Ávila-Román, Javier; Talero, Elena; de Los Reyes, Carolina; García-Mauriño, Sofía; Motilva, Virginia

2018-02-01

Oxylipins (OXLs) are bioactive molecules generated by the oxidation of fatty acids that promote the resolution of acute inflammation and prevent chronic inflammatory processes through molecular mechanisms that are not well known. We have previously reported the anti-inflammatory activity of microalgae-derived OXLs and OXL-containing biomass in two inflammatory bowel disease (IBD) models: 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis and TNBS-induced recurrent colitis. In this study, we examined the in vitro anti-inflammatory mechanism of action of the most abundant OXLs isolated from Chlamydomonas debaryana (13S-HOTE and 13S-HODE) and Nannochloropsis gaditana (15S-HEPE). These OXLs decreased IL-1β and IL-6 pro-inflammatory cytokines production as well as iNOS and COX-2 expression levels in THP-1 macrophages. In addition, OXLs decreased IL-8 production in HT-29 colon cells, the major chemokine produced by these cells. The interaction of OXLs with NFκB and PPAR-γ signaling pathways was studied by confocal microscopy. In THP-1 macrophages and HT-29 colon cells, stimulated by LPS and TNFα respectively, a pre-treatment with 13S-HOTE, 13S-HODE and 15S-HEPE (100μM) resulted in a lower nuclear presence of NFκB in both cell lines. The study of the subcellular localization of PPAR-γ showed that the treatment of THP-1 and HT-29 cells with these OXLs caused the migration of PPAR-γ into the nucleus. Colocalization analysis of both transcription factors in LPS-stimulated THP-1 macrophages showed that the pre-treatment with 13S-HOTE, 13S-HODE or 15S-HEPE lowered nuclear colocalization similar to control value, and increased cytosolic localization above control level. These results indicate that these OXLs could act as agonist of PPAR-γ and consequently inhibit NFκB signaling pathway activation, thus lowering the production of inflammatory markers, highlighting the therapeutic potential of these OXLs in inflammatory diseases such as IBD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

PubMed Central

Kim, Ki Rim; Jeong, Chan-Kwon; Park, Kwang-Kyun; Choi, Jong-Hoon; Park, Jung Han Yoon; Lim, Soon Sung; Chung, Won-Yoon

2010-01-01

The anti-inflammatory activity of licorice (LE) and roated licorice (rLE) extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA) model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE. PMID:20300198

Forced swimming sabotages the morphological and synaptic maturation of newborn granule neurons and triggers a unique pro-inflammatory milieu in the hippocampus.

PubMed

Llorens-Martín, María; Jurado-Arjona, Jerónimo; Bolós, Marta; Pallas-Bazarra, Noemí; Ávila, Jesús

2016-03-01

Recent experimental data suggest that mood disorders are related to inflammatory phenomena and have led to the "inflammatory hypothesis of depression". Given that the hippocampus is one of the most affected areas in these disorders, we used a model of acute stress (the Porsolt test) to evaluate the consequences of forced swimming on two crucial events related to the pathophysiology of major depression: the functional maturation of newborn granule neurons; and the hippocampal inflammatory milieu. Using PSD95:GFP-expressing retroviruses, we found that forced swimming selectively alters the dendritic morphology of newborn neurons and impairs their connectivity by reducing the number and volume of their postsynaptic densities. In addition, acute stress triggered a series of morphological changes in microglial cells, together with an increase in microglial CD68 expression, thus suggesting the functional and morphological activation of this cell population. Furthermore, we observed an intriguing change in the hippocampal inflammatory milieu in response to forced swimming. Importantly, the levels of several molecules affected by acute stress (such as Interleukin-6 and eotaxin) have been described to also be altered in patients with depression and other mood disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice

USDA-ARS?s Scientific Manuscript database

Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesiz...

Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option?

PubMed

Ortiz, Gustavo; Salica, Juan P; Chuluyan, Eduardo H; Gallo, Juan E

2014-11-18

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.

N-acetyl cysteine improves the effects of corticosteroids in a mouse model of chlorine-induced acute lung injury.

PubMed

Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders; Jonasson, Sofia

2015-02-03

Chlorine (Cl2) causes tissue damage and a neutrophilic inflammatory response in the airways manifested by pronounced airway hyperreactivity (AHR). The importance of early anti-inflammatory treatment has previously been addressed. In the previous study, both high-dose and low-dose of dexamethasone (DEX) decreased the risk of developing delayed effects, such as persistent lung injuries, while only high-dose treatment could significantly counteract acute-phase effects. One aim of this study was to evaluate whether a low-dose of DEX in combination with the antioxidant N-acetyl cysteine (NAC) and if different treatments (Triptolide, Reparixin and Rolipram) administered 1h after Cl2-exposure could improve protection against acute lung injury in Cl2-exposed mice. BALB/c mice were exposed to 300 ppm Cl2 during 15 min. Assessment of AHR and inflammatory cells in bronchoalveolar lavage was analyzed 24h post exposure. Neither of DEX nor NAC reduced the AHR and displayed only minor effects on inflammatory cell influx when given as separate treatments. When given in combination, a protective effect on AHR and a significant reduction in inflammatory cells (neutrophils) was observed. Neither of triptolide, Reparixin nor Rolipram had an effect on AHR but Triptolide had major effect on the inflammatory cell influx. Treatments did not reduce the concentration of either fibrinogen or plasminogen activator inhibitor-1 in serum, thereby supporting the theory that the inflammatory response is not solely limited to the lung. These results provide a foundation for future studies aimed at identifying new concepts for treatment of chemical-induced lung injury. Studies addressing combination of anti-inflammatory and antioxidant treatment are highly motivated. Copyright © 2014. Published by Elsevier Ireland Ltd.

Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases?

PubMed

Iida, Tomoya; Wagatsuma, Kohei; Hirayama, Daisuke; Nakase, Hiroshi

2017-12-21

Osteopontin (OPN) is involved in a variety of biological processes, including bone remodeling, innate immunity, acute and chronic inflammation, and cancer. The expression of OPN occurs in various tissues and cells, including intestinal epithelial cells and immune cells such as macrophages, dendritic cells, and T lymphocytes. OPN plays an important role in the efficient development of T helper 1 immune responses and cell survival by inhibiting apoptosis. The association of OPN with apoptosis has been investigated. In this review, we described the role of OPN in inflammatory gastrointestinal and liver diseases, focusing on the association of OPN with apoptosis. OPN changes its association with apoptosis depending on the type of disease and the phase of disease activity, acting as a promoter or a suppressor of inflammation and inflammatory carcinogenesis. It is essential that the roles of OPN in those diseases are elucidated, and treatments based on its mechanism are developed.

Vitreous web after pars plana vitrectomy and bevacizumab with fluid-air exchange.

PubMed

Chiang, Allen; Reddy, Shantan; Tsui, Irena; Hubschman, Jean-Pierre

2011-01-01

Intravitreal bevacizumab may result in intraocular inflammation of infectious and non-infectious etiology. Appropriate recognition of a sterile process can circumvent unnecessary treatment for endophthalmitis. Observational case report. A marked web-like inflammatory response within the vitreous following intraoperative intravitreal bevacizumab is described in a patient with pre-proliferative diabetic retinopathy, macular edema, and epiretinal membrane who underwent pars plana vitrectomy, membrane peel, endolaser, and fluid-air exchange. Wide-field fundus photography captured the full extent of this reaction. On post-operative day one, the patient presented with vitreous opacities in the form of a web of multiple white strands inferior to an air bubble, with minimal anterior or vitreous cell. At one week, the inflammatory reaction had completely resolved. Existing reports of intraocular inflammation following intravitreal bevacizumab range from uveitis to infectious endophthalmitis. With wide-field fundus imaging, we report an acute, marked web-like inflammatory response following intraoperative intravitreal bevacizumab that resolved spontaneously.

Inflammasome Activity in Non-Microbial Lung Inflammation

PubMed Central

Ather, Jennifer L.; Martin, Rebecca A.; Ckless, Karina; Poynter, Matthew E.

2015-01-01

The understanding of interleukin-1 (IL-1) family cytokines in inflammatory disease has rapidly developed, due in part to the discovery and characterization of inflammasomes, which are multi-subunit intracellular protein scaffolds principally enabling recognition of a myriad of cellular stimuli, leading to the activation of caspase-1 and the processing of IL-1β and IL-18. Studies continue to elucidate the role of inflammasomes in immune responses induced by both microbes and environmental factors. This review focuses on the current understanding of inflammasome activity in the lung, with particular focus on the non-microbial instigators of inflammasome activation, including inhaled antigens, oxidants, cigarette smoke, diesel exhaust particles, mineral fibers, and engineered nanomaterials, as well as exposure to trauma and pre-existing inflammatory conditions such as metabolic syndrome. Inflammasome activity in these sterile inflammatory states contribute to diseases including asthma, chronic obstructive disease, acute lung injury, ventilator-induced lung injury, pulmonary fibrosis, and lung cancer. PMID:25642415

Acute asthma during pregnancy.

PubMed Central

Stenius-Aarniala, B. S.; Hedman, J.; Teramo, K. A.

1996-01-01

BACKGROUND: Acute asthma during pregnancy is potentially dangerous to the fetus. The aim of this study was to investigate the effect of an acute attack of asthma during pregnancy on the course of pregnancy or delivery, or the health of the newborn infant, and to identify undertreatment as a possible cause of the exacerbations. METHODS: Five hundred and four pregnant asthmatic subjects were prospectively followed and treated. The data on 47 patients with an attack of asthma during pregnancy were compared with those of 457 asthmatics with no recorded acute exacerbation and with 237 healthy parturients. RESULTS: Of 504 asthmatics, 177 patients were not initially treated with inhaled corticosteroids. Of these, 17% had an acute attack compared with only 4% of the 257 patients who had been on inhaled anti-inflammatory treatment from the start of pregnancy. There were no differences between the groups as to length of gestation, length of the third stage of labour, or amount of haemorrhage after delivery. No differences were observed between pregnancies with and without an exacerbation with regard to relative birth weight, incidence of malformations, hypoglycaemia, or need for phototherapy for jaundice during the neonatal period. CONCLUSIONS: Patients with inadequate inhaled anti-inflammatory treatment during pregnancy run a higher risk of suffering an acute attack of asthma than those treated with an anti-inflammatory agent. However, if the acute attack of asthma is relatively mild and promptly treated, it does not have a serious effect on the pregnancy, delivery, or the health of the newborn infant. PMID:8733495

Repeated, but Not Acute, Stress Suppresses Inflammatory Plasma Extravasation

NASA Astrophysics Data System (ADS)

Strausbaugh, Holly J.; Dallman, Mary F.; Levine, Jon D.

1999-12-01

Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of plasma extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of plasma extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial plasma extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of plasma extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases.

The effects of low-dose X-irradiation on the oxidative burst in stimulated macrophages.

PubMed

Schaue, D; Marples, B; Trott, K R

2002-07-01

Local irradiation with a dose of around 0.5 Gy is an effective treatment of acute necrotizing inflammations. The hypothesis that low doses of X-rays modulate the oxidative burst in activated macrophages, which plays a major role in the acute inflammatory process, was tested. Murine RAW 264.7 macrophages were stimulated with LPS/gammaIFN, PMA or zymosan and oxidative burst was measured using either DCFH-DA or by reduction of cytochrome-C. Radiation doses of 0.3-10 Gy were given shortly before or after stimulation. Low X-ray doses of <1 Gy significantly reduced the oxidative burst in activated macrophages, whereas higher doses had little effect on oxidative burst. The modulation of oxidative burst by low radiation doses may contribute to the therapeutic effectiveness of low-dose radiotherapy of acute necrotizing inflammations.

Surgical inflammatory stress: the embryo takes hold of the reins again

PubMed Central

2013-01-01

The surgical inflammatory response can be a type of high-grade acute stress response associated with an increasingly complex trophic functional system for using oxygen. This systemic neuro-immune-endocrine response seems to induce the re-expression of 2 extraembryonic-like functional axes, i.e. coelomic-amniotic and trophoblastic-yolk-sac-related, within injured tissues and organs, thus favoring their re-development. Accordingly, through the up-regulation of two systemic inflammatory phenotypes, i.e. neurogenic and immune-related, a gestational-like response using embryonic functions would be induced in the patient’s injured tissues and organs, which would therefore result in their repair. Here we establish a comparison between the pathophysiological mechanisms that are produced during the inflammatory response and the physiological mechanisms that are expressed during early embryonic development. In this way, surgical inflammation could be a high-grade stress response whose pathophysiological mechanisms would be based on the recapitulation of ontogenic and phylogenetic-related functions. Thus, the ultimate objective of surgical inflammation, as a gestational process, is creating new tissues/organs for repairing the injured ones. Since surgical inflammation and early embryonic development share common production mechanisms, the factors that hamper the wound healing reaction in surgical patients could be similar to those that impair the gestational process. PMID:23374964

[Puncture scrotostomy--a treatment method in acute inflammatory diseases of the scrotal organs].

PubMed

Shapoval, V I; Asimov, D A; Lesovoĭ, V N

1989-01-01

A method for the treatment of acute inflammatory diseases of the scrotal organs by means of puncture scrotostomy, which consists in passing the indwelling micro-irrigator into a cavity of the serous sheath of the testis and epididymis and administration via this route of antibacterial and resolving preparations for 4-5 days, is suggested. A method approved in treatment of 45 patients permits to avoid surgical intervention, and is highly effective.

Hydroalcoholic extract of Stevia rebaudiana bert. leaves and stevioside ameliorates lipopolysaccharide induced acute liver injury in rats.

PubMed

S, Latha; Chaudhary, Sheetal; R S, Ray

2017-11-01

Oxidative stress and hepatic inflammatory response is primarily implicated in the pathogenesis of LPS induced acute liver injury. Stevioside, a diterpenoidal glycoside isolated from the Stevia rebaudiana leaves, exerts potent anti-oxidant, anti-inflammatory and immunomodulatory activities. The present study was aimed to investigate the hepatoprotective effect of hydroalcoholic extract of Stevia rebaudiana leaves (STE EXT) and its major phytochemical constituent, stevioside (STE) in LPS induced acute liver injury. The hepatoprotective activity of STE EXT (500mg/kg p.o) and STE (250mg/kg p.o) was investigated in lipopolysaccharide (LPS 5mg/kg i.p.) induced acute liver injury in male wistar rats. Our results revealed that both STE EXT and STE treatment ameliorated LPS induced hepatic oxidative stress, evident from altered levels of reduced SOD, Catalase, GSH, MDA, NO. Histopathological observations revealed that both STE EXT and STE attenuated LPS induced structural changes and hepatocellular apoptosis providing additional evidence for its hepatoprotective effect. Further, STE EXT and STE significantly restored the elevated serum and tissue levels of AST and ALT in LPS treated rats. Furthermore, both STE EXT and STE rescued hepatocellular dysfunctions to normal by altering the level of proinflammatory cytokines such as TNF-α, IL-1β and IL-6 exhibiting its anti-inflammatory potential. In conclusion, both STE EXT and STE demonstrated excellent hepatoprotective effects against endotoxemia induced acute liver injury possibly through suppression of hepatic inflammatory response and oxidative stress, attributing to its medicinal importance in treating various liver ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway.

PubMed

Barcelos, Rômulo Pillon; Bresciani, Guilherme; Cuevas, Maria José; Martínez-Flórez, Susana; Soares, Félix Alexandre Antunes; González-Gallego, Javier

2017-07-01

Nonsteroidal anti-inflammatory drugs, such as diclofenac, are widely used to treat inflammation and pain in several conditions, including sports injuries. This study analyzes the influence of diclofenac on the toll-like receptor-nuclear factor kappa B (TLR-NF-κB) pathway in skeletal muscle of rats submitted to acute eccentric exercise. Twenty male Wistar rats were divided into 4 groups: control-saline, control-diclofenac, exercise-saline, and exercise-diclofenac. Diclofenac or saline were administered for 7 days prior to an acute eccentric exercise bout. The inflammatory status was evaluated through mRNA levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNF-α), and protein content of COX-2, IL-6, and TNF-α in vastus lateralis muscle. Data obtained showed that a single bout of eccentric exercise significantly increased COX-2 gene expression. Similarly, mRNA expression and protein content of other inflammation-related genes also increased after the acute exercise. However, these effects were attenuated in the exercise + diclofenac group. TLR4, myeloid differentiation primary response gene 88 (MyD88), and p65 were also upregulated after the acute eccentric bout and the effect was blunted by the anti-inflammatory drug. These findings suggest that pretreatment with diclofenac may represent an effective tool to ameliorate the pro-inflammatory status induced by acute exercise in rat skeletal muscle possibly through an attenuation of the TLR4-NF-κB signaling pathway.

Preventive rather than therapeutic treatment with high fiber diet attenuates clinical and inflammatory markers of acute and chronic DSS-induced colitis in mice.

PubMed

Silveira, Ana Letícia Malheiros; Ferreira, Adaliene Versiani Matos; de Oliveira, Marina Chaves; Rachid, Milene Alvarenga; da Cunha Sousa, Larissa Fonseca; Dos Santos Martins, Flaviano; Gomes-Santos, Ana Cristina; Vieira, Angelica Thomaz; Teixeira, Mauro Martins

2017-02-01

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with important impact on global health. Prebiotic and probiotic strategies are thought to be useful in the context of experimental IBD. Here, we compared the effects of preventive versus therapeutic treatment with a high fiber diet (prebiotic) in combination or not with Bifidobacterium longum (probiotic) in a murine model of chronic colitis. Colitis was induced by adding dextran sulfate sodium (DSS) to drinking water for 6 days (acute colitis) or for 5 cycles of DSS (chronic colitis). Administration of the high fiber diet protected from acute colitis. Protection was optimal when diet was started 20 days prior to DSS. A 5-day pretreatment with acetate, a short-chain fatty acid, provided partial protection against acute colitis. In chronic colitis, pretreatment with the high fiber diet attenuated clinical and inflammatory parameters of disease. However, when the treatment with the high fiber diet started after disease had been established, overall protection was minimal. Similarly, delayed treatment with acetate or B. longum did not provide any protection even when the probiotic was associated with the high fiber diet. Preventive use of a high fiber diet or acetate clearly protects mice against acute and chronic damage induced by DSS in mice. However, protection is lost when therapies are initiated after disease has been established. These results suggest that any therapy aimed at modifying the gut environment (e.g., prebiotic or probiotic strategies) should be given early in the course of disease.

Synthesis and Study of Analgesic and Anti-inflammatory Activities of Amide Derivatives of Ibuprofen.

PubMed

Ahmadi, Abbas; Khalili, Mohsen; Olama, Zahra; Karami, Shirin; Nahri-Niknafs, Babak

2017-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide and represent a mainstay in the therapy of acute and chronic pain and inflammation. The traditional NSAIDs like ibuprofen (I) contain free carboxylic acid group which can produce gastrointestinal (GI) damage for long-term use. In order to obtain the novel NSAIDs with less side effects; carboxylic acid moiety has been modified into various amide groups which is the most active area of research in this family. In this research, synthesis of various pharmacological heterocyclic amides of ibuprofen is described. All the new compounds were tested for their analgesic and anti-inflammatory activities in mice and compared with standard (Ibuprofen) and control (saline) groups. The results revealed that all the synthesized compounds (III-VI) exhibited more analgesic and anti-inflammatory activities in tail immersion (as a model of acute thermal pain), formalin (as a model of acute chemical and chronic pain) and paw edema (as a model of acute inflammation) tests when compared with standard and control animals. These pharmacological activities were significant for VI compared to other new compounds (III-V) which may be concern to more effective role of morpholin for the reduction of pain and inflammation compared to other used heterocyclic amines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

PubMed

Hoff Brait, Débora Regina; Mattos Vaz, Márcia Soares; da Silva Arrigo, Jucicléia; Borges de Carvalho, Luciana Noia; Souza de Araújo, Flávio Henrique; Vani, Juliana Miron; da Silva Mota, Jonas; Cardoso, Claudia Andrea Lima; Oliveira, Rodrigo Juliano; Negrão, Fábio Juliano; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2015-12-01

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of LPS-induced immune activation prior to trauma exposure on PTSD-like symptoms in mice.

PubMed

Deslauriers, Jessica; van Wijngaarde, Myrthe; Geyer, Mark A; Powell, Susan; Risbrough, Victoria B

2017-04-14

The prevalence of posttraumatic stress disorder (PTSD) is high in the armed services, with a rate up to 20%. Multiple studies have associated markers of inflammatory signaling prior to trauma with increased risk of PTSD, suggesting a potential role of the immune system in the development of this psychiatric disorder. One question that arises is if "priming" the immune system before acute trauma alters the stress response and increases enduring effects of trauma. We investigated the time course of inflammatory response to predator stress, a robust stressor that induces enduring PTSD-like behaviors, and the modulation of these effects via prior immune activation with the bacterial endotoxin, lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist. Mice exposed to predator stress exhibited decreased pro-/anti-inflammatory balance in the brain 6h after stress, suggesting that predator exposure acutely suppressed the immune system by increasing anti-inflammatory cytokines levels. Acute immune activation with LPS before a single predator stress did not alter the enduring avoidance behavior in stressed mice. Our findings suggest that acute inflammation, at least via TLR4 activation, is not sufficient to increase susceptibility for PTSD-like behaviors in this model. Future studies will examine if chronic inflammation is required to induce similar immune changes to those observed in PTSD patients in this model. Published by Elsevier B.V.

Treatment of Acute Pelvic Inflammatory Disease

PubMed Central

Sweet, Richard L.

2011-01-01

Pelvic inflammatory disease (PID), one of the most common infections in nonpregnant women of reproductive age, remains an important public health problem. It is associated with major long-term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, treatment of acute PID and its complications incurs substantial health care costs. Prevention of these long-term sequelae is dependent upon development of treatment strategies based on knowledge of the microbiologic etiology of acute PID. It is well accepted that acute PID is a polymicrobic infection. The sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, are present in many cases, and microorganisms comprising the endogenous vaginal and cervical flora are frequently associated with PID. This includes anaerobic and facultative bacteria, similar to those associated with bacterial vaginosis. Genital tract mycoplasmas, most importantly Mycoplasma genitalium, have recently also been implicated as a cause of acute PID. As a consequence, treatment regimens for acute PID should provide broad spectrum coverage that is effective against these microorganisms. PMID:22228985

Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models.

PubMed

Hu, Fuliang; Hepburn, H R; Li, Yinghua; Chen, M; Radloff, S E; Daya, S

2005-09-14

The anti-inflammatory effects of ethanol (EEP) and water (WSD) extracts in ICR mice and Wistar rats were analyzed. Both WSD and EEP exhibited significant anti-inflammatory effects in animal models with respect to thoracic capillary vessel leakage in mice, carrageenan-induced oedema, carrageenan-induced pleurisy, acute lung damage in rats. The mechanisms for the anti-inflammatory effects probably involve decreasing prostaglandin-E(2) (PGE(2)) and nitric oxide (NO) levels. In rats with Freund's complete adjuvant (FCA) induced arthritis, propolis extracts significantly inhibited the increase of interleukin-6 (IL-6) in inflamed tissues, but had no significant effect on levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). The results are consistent with the interpretation that EEP and WSD may exert these effects by inhibiting the activation and differentiation of mononuclear macrophages.

Equine respiratory pharmacology.

PubMed

Foreman, J H

1999-12-01

Differentiation of diseases of the equine respiratory tract is based on history, clinical signs, auscultation, endoscopy, imaging, and sampling of airway exudate. Upper respiratory therapies include surgical correction of airway obstructions; flushing of localized abscesses (strangles), guttural pouch disease, or sinusitis; and oral or parenteral antibiotic and anti-inflammatory therapy if deemed necessary. Pneumonia usually is treated with antimicrobials, anti-inflammatories, and bronchodilators. Pleural drainage is indicated if significant pleural effusion is present. The most commonly used therapies for early inflammatory and chronic allergic obstructive conditions include bronchodilators and anti-inflammatories. Acute respiratory distress, particularly acute pulmonary edema, is treated with diuretics (usually furosemide), intranasal oxygen, bronchodilators, corticosteroids, and alleviation of the underlying cause. Furosemide also had been used in North America as a race-day preventative for exercise-induced pulmonary hemorrhage (EIPH), but recent data have shown that furosemide may be a performance-enhancing agent itself.

Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice

PubMed Central

Doi, Kent; Okamoto, Koji; Negishi, Kousuke; Suzuki, Yoshifumi; Nakao, Akihide; Fujita, Toshiro; Toda, Akiko; Yokomizo, Takehiko; Kita, Yoshihiro; Kihara, Yasuyuki; Ishii, Satoshi; Shimizu, Takao; Noiri, Eisei

2006-01-01

Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells. PMID:16651609

Impact of acute exacerbations on platelet reactivity in chronic obstructive pulmonary disease patients.

PubMed

Muñoz-Esquerre, Mariana; Ferreiro, José Luis; Huertas, Daniel; Marcano, Ana Lucrecia; López-Sánchez, Marta; Roura, Gerard; Gómez-Hospital, Joan Antoni; Dorca, Jordi; Cequier, Angel; Santos, Salud

2018-01-01

A higher risk of atherothrombotic cardiovascular events, which are platelet-driven processes, has been described during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the relevance of platelet reactivity during AECOPD and whether this is affected by antiplatelet agents are not fully elucidated to date. This study aimed to evaluate whether platelet reactivity is augmented during an exacerbation in COPD patients with and without antiplatelet therapy and its association with systemic inflammatory parameters. Prospective, observational, ex vivo investigation was conducted in consecutive patients suffering an exacerbation of COPD. Platelet reactivity was assessed during AECOPD and at stable state. Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay expressed as P2Y 12 reactivity index (PRI), 2) multiple electrode aggregometry and 3) optical aggregometry. Systemic inflammatory parameters such as leukocyte count, interleukin-6 and fibrinogen were also assessed. Higher platelet reactivity was observed during AECOPD compared to stability measured by vasodilator-stimulated phosphoprotein (PRI: 75.2%±1.9% vs 68.8%±2.4%, p =0.001). This augmented platelet aggregability was also observed in the subset of patients on antiplatelet therapy (PRI: 72.8%±3.1% vs 61.7%±7.5%, p =0.071). Consistent findings were observed with all other platelet function tests. Patients with greater enhancement of inflammatory markers during AECOPD were more likely to present a higher increase in platelet reactivity. Platelet reactivity is increased during AECOPD, which may contribute to the augmented cardiovascular risk of these patients. Additionally, the increase in platelet reactivity might be associated with an increment in inflammatory markers during exacerbations.

A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1)

PubMed Central

Ritz, Thomas; Rosenfield, David; St. Laurent, Chris D.; Trueba, Ana F.; Werchan, Chelsey A.; Vogel, Pia D.; Auchus, Richard J.; Reyes-Serratos, Eduardo

2017-01-01

Calcium-binding protein spermatid-specific 1 (CABS1) is expressed in the human submandibular gland and has an anti-inflammatory motif similar to that in submandibular rat 1 in rats. Here, we investigate CABS1 in human saliva and its association with psychological and physiological distress and inflammation in humans. Volunteers participated across three studies: 1) weekly baseline measures; 2) a psychosocial speech and mental arithmetic stressor under evaluative threat; and 3) during academic exam stress. Salivary samples were analyzed for CABS1 and cortisol. Additional measures included questionnaires of perceived stress and negative affect; exhaled nitric oxide; respiration and cardiac activity; lung function; and salivary and nasal inflammatory markers. We identified a CABS1 immunoreactive band at 27 kDa in all participants and additional molecular mass forms in some participants. One week temporal stability of the 27-kDa band was satisfactory (test–retest reliability estimate = 0.62–0.86). Acute stress increased intensity of 18, 27, and 55 kDa bands; 27-kDa increases were associated with more negative affect and lower heart rate, sympathetic activity, respiration rate, and minute ventilation. In both acute and academic stress, changes in 27 kDa were positively associated with salivary cortisol. The 27-kDa band was also positively associated with VEGF and salivary leukotriene B4 levels. Participants with low molecular weight CABS1 bands showed reduced habitual stress and negative affect in response to acute stress. CABS1 is readily detected in human saliva and is associated with psychological and physiological indicators of stress. The role of CABS1 in inflammatory processes, stress, and stress resilience requires careful study. PMID:28381457

Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

PubMed Central

Coelho, Ana Maria M.; Sampietre, Sandra; Patzina, Rosely; Jukemura, Jose; Cunha, Jose Eduardo M.; Machado, Marcel C.C.

2007-01-01

Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy. PMID:18345325

/sup 67/Ga-citrate uptake by the parotid glands in sarcoidosis. [Effectiveness for differential diagnosis

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

Wiener, S.N.; Patel, B.P.

1979-03-01

Bilateral accumulation of /sup 66/Ga-citrate by the parotid glands was observed in 9 of 27 patients (33%) with sarcoidosis and in a subgroup of 12 with systemic symptoms such as fever or clinically acute, progressive disease (75%). Asymptomatic patients or those with probable sarcoidosis associated with hilar and/or paratracheal adenopathy will not have parotid uptake. Similarly, uptake seldom occurs in normal patients or in those with untreated lymphoma or Hodgkin disease. If other inflammatory or granulomatous processes such as tuberculosis can be excluded, and if there is no history of head and neck irradiation, then this finding in acutely illmore » patients suggests sarcoidosis.« less

ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly.

PubMed

Klyne, David M; Barbe, Mary F; van den Hoorn, Wolbert; Hodges, Paul W

2018-04-01

Prospective longitudinal study. To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related. Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months. CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery. This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific elevation of TNF, along with depressive symptoms, was associated with bad recovery. Depression and TNF may have a two-way relationship. These slides can be retrieved under Electronic Supplementary Material.

Involvement of TGF-β1/Smad3 Signaling in Carbon Tetrachloride-Induced Acute Liver Injury in Mice

PubMed Central

Niu, Liman; Cui, Xueling; Qi, Yan; Xie, Dongxue; Wu, Qian; Chen, Xinxin; Ge, Jingyan; Liu, Zhonghui

2016-01-01

Transforming growth factor-beta1 (TGF-β1) is a major factor in pathogenesis of chronic hepatic injury. Carbon tetrachloride (CCl4) is a liver toxicant, and CCl4-induced liver injury in mouse is a classical animal model of chemical liver injury. However, it is still unclear whether TGF-β1 is involved in the process of CCl4-induced acute chemical liver injury. The present study aimed to evaluate the role of TGF-β1 and its signaling molecule Smad3 in the acute liver injury induce by CCl4. The results showed that CCl4 induced acute liver injury in mice effectively confirmed by H&E staining of liver tissues, and levels of not only liver injury markers serum ALT and AST, but also serum TGF-β1 were elevated significantly in CCl4-treated mice, compared with the control mice treated with olive oil. Our data further revealed that TGF-β1 levels in hepatic tissue homogenate increased significantly, and type II receptor of TGF-β (TβRII) and signaling molecules Smad2, 3, mRNA expressions and Smad3 and phospho-Smad3 protein levels also increased obviously in livers of CCl4-treated mice. To clarify the effect of the elevated TGF-β1/Smad3 signaling on CCl4-induced acute liver injury, Smad3 in mouse liver was overexpressed in vivo by tail vein injection of Smad3-expressing plasmids. Upon CCl4 treatment, Smad3-overexpressing mice showed more severe liver injury identified by H&E staining of liver tissues and higher serum ALT and AST levels. Simultaneously, we found that Smad3-overexpressing mice treated with CCl4 showed more macrophages and neutrophils infiltration in liver and inflammatory cytokines IL-1β and IL-6 levels increment in serum when compared with those in control mice treated with CCl4. Moreover, the results showed that the apoptosis of hepatocytes increased significantly, and apoptosis-associated proteins Bax, cytochrome C and the cleaved caspase 3 expressions were up-regulated in CCl4-treated Smad3-overexpressing mice as well. These results suggested that TGF-β1/Smad3 signaling was activated during CCl4-induced acute liver injury in mice, and Smad3 overexpression aggravated acute liver injury by promoting inflammatory cells infiltration, inflammatory cytokines release and hepatocytes apoptosis. In conclusion, the activation of TGF-β signaling contributes to the CCl4-induced acute liver injury. Thus, TGF-β1/Smad3 may serve as a potential target for acute liver injury therapy. PMID:27224286

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research.

PubMed

Maes, Michael; Nowak, Gabriel; Caso, Javier R; Leza, Juan Carlos; Song, Cai; Kubera, Marta; Klein, Hans; Galecki, Piotr; Noto, Cristiano; Glaab, Enrico; Balling, Rudi; Berk, Michael

2016-07-01

Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.

Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial.

PubMed

Kuebler, Ulrike; Arpagaus, Angela; Meister, Rebecca E; von Känel, Roland; Huber, Susanne; Ehlert, Ulrike; Wirtz, Petra H

2016-10-01

Flavanol-rich dark chocolate consumption relates to lower risk of cardiovascular mortality, but underlying mechanisms are elusive. We investigated the effect of acute dark chocolate consumption on inflammatory measures before and after stress. Healthy men, aged 20-50years, were randomly assigned to a single intake of either 50g of flavanol-rich dark chocolate (n=31) or 50g of optically identical flavanol-free placebo-chocolate (n=34). Two hours after chocolate intake, both groups underwent the 15-min Trier Social Stress Test. We measured DNA-binding-activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, as well as plasma and whole blood mRNA levels of the pro-inflammatory cytokines IL-1β and IL-6, and the anti-inflammatory cytokine IL-10, prior to chocolate intake as well as before and several times after stress. We also repeatedly measured the flavanol epicatechin and the stress hormones epinephrine and cortisol in plasma and saliva, respectively. Compared to the placebo-chocolate-group, the dark-chocolate-group revealed a marginal increase in IL-10 mRNA prior to stress (p=0.065), and a significantly blunted stress reactivity of NF-κB-BA, IL-1β mRNA, and IL-6 mRNA (p's⩽0.036) with higher epicatechin levels relating to lower pro-inflammatory stress reactivity (p's⩽0.033). Stress hormone changes to stress were controlled. None of the other measures showed a significant chocolate effect (p's⩾0.19). Our findings indicate that acute flavanol-rich dark chocolate exerts anti-inflammatory effects both by increasing mRNA expression of the anti-inflammatory cytokine IL-10 and by attenuating the intracellular pro-inflammatory stress response. This mechanism may add to beneficial effects of dark chocolate on cardiovascular health. Copyright © 2016 Elsevier Inc. All rights reserved.

Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

PubMed

Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain. Georg Thieme Verlag KG Stuttgart · New York.

Modulation of Brain Hemichannels and Gap Junction Channels by Pro-Inflammatory Agents and Their Possible Role in Neurodegeneration

PubMed Central

Sáez, Pablo J.; Shoji, Kenji F.; Schalper, Kurt A.; Palacios–Prado, Nicolás; Velarde, Victoria; Giaume, Christian; Bennett, Michael V.L.; Sáez, Juan C.

2009-01-01

Abstract In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process. Antiox. Redox Signal. 11, 369–399. PMID:18816186

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo

PubMed Central

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-01-01

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25–100 μm wide) and minibeams (200–800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a+ thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool. PMID:27640676

Immunomodulatory therapies for acute pancreatitis

PubMed Central

Li, Jing; Yang, Wen-Juan; Huang, Lu-Ming; Tang, Cheng-Wei

2014-01-01

It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. PMID:25493006

[Axonopathy in the pathogenesis of multiple sclerosis, peripheral diffuse and local motor neuropathies and motor neuron disease].

PubMed

Merkulov, Iu A; Merkulova, D M; Iosifova, O A; Zavalishin, I A

2010-01-01

Two hundreds and seventy-six patients including 43 patients with multiple sclerosis, 24 - with acute inflammatory demyelinating polyneuropathy (AIDP), 144 - with chronic inflammatory demyelinating polyneuropathy (CIDP), 27 - with motor multifocal neuropathy (MMN), 38 - with lateral amyotrophic sclerosis (LAS) have been examined. Symptoms of axonal degeneration, manifested in denervation phenomena in both clinical and instrumental studies (electromyography, transcranial magnetic stimulation, MRT), were revealed in all groups of patients. The formation of excitation conduction blocks is an universal pathophysiological mechanism of the axonopathy development in AIDP, CIDP, MMN and LAS. Symptoms of axonopathy and peripheral demyelinization in patients with multiple sclerosis and LAS suggest the possibility of transformation of immunopathological process from the central nervous system to the peripheral one.

Impaired Resolution of Inflammation in Alzheimer's Disease: A Review.

PubMed

Whittington, Robert A; Planel, Emmanuel; Terrando, Niccolò

2017-01-01

Alzheimer's disease (AD) remains the leading cause of dementia worldwide, and over the last several decades, the role of inflammation in the pathogenesis of this neurodegenerative disorder has been increasingly elucidated. The initiation of the acute inflammatory response is counterbalanced by an active process termed resolution. This process is designed to restore homeostasis and promote tissue healing by the activation of neutrophilic apoptosis, promotion of neutrophil clearance by macrophages, and increasing anti-inflammatory cytokine levels, while concurrently leading to a diminution in pro-inflammatory mediators. The switch from the initiation to the resolution phase of inflammation is initially characterized by increased production of arachidonic acid-derived pro-resolving lipoxins and decreases in pro-inflammatory prostaglandin and leukotriene levels, subsequently followed by increases in specialized pro-resolving lipid mediators derived from omega-3 fatty acids (ω-3 FAs). There is mounting evidence that in AD, the resolution of inflammation is impaired, resulting in chronic inflammation and the exacerbation of the AD-related pathology. In this review, we examine preclinical and clinical evidence supporting the hypothesis that AD is a neurodegenerative disorder where the impairment or failure of resolution contributes to the disease process. Moreover, we review the literature supporting the potential therapeutic role of ω-3 FAs and specialized pro-resolving lipid mediators in the management of the disease. Lastly, we highlight areas that could strengthen the association of failed resolution to AD and should, therefore, be the focus of future scientific investigations in this research field.

Impaired Resolution of Inflammation in Alzheimer’s Disease: A Review

PubMed Central

Whittington, Robert A.; Planel, Emmanuel; Terrando, Niccolò

2017-01-01

Alzheimer’s disease (AD) remains the leading cause of dementia worldwide, and over the last several decades, the role of inflammation in the pathogenesis of this neurodegenerative disorder has been increasingly elucidated. The initiation of the acute inflammatory response is counterbalanced by an active process termed resolution. This process is designed to restore homeostasis and promote tissue healing by the activation of neutrophilic apoptosis, promotion of neutrophil clearance by macrophages, and increasing anti-inflammatory cytokine levels, while concurrently leading to a diminution in pro-inflammatory mediators. The switch from the initiation to the resolution phase of inflammation is initially characterized by increased production of arachidonic acid-derived pro-resolving lipoxins and decreases in pro-inflammatory prostaglandin and leukotriene levels, subsequently followed by increases in specialized pro-resolving lipid mediators derived from omega-3 fatty acids (ω-3 FAs). There is mounting evidence that in AD, the resolution of inflammation is impaired, resulting in chronic inflammation and the exacerbation of the AD-related pathology. In this review, we examine preclinical and clinical evidence supporting the hypothesis that AD is a neurodegenerative disorder where the impairment or failure of resolution contributes to the disease process. Moreover, we review the literature supporting the potential therapeutic role of ω-3 FAs and specialized pro-resolving lipid mediators in the management of the disease. Lastly, we highlight areas that could strengthen the association of failed resolution to AD and should, therefore, be the focus of future scientific investigations in this research field. PMID:29163531

Docosahexaenoic Acid Inhibits Cerulein-Induced Acute Pancreatitis in Rats

PubMed Central

Jeong, Yoo Kyung; Lee, Sle; Lim, Joo Weon

2017-01-01

Oxidative stress is an important regulator in the pathogenesis of acute pancreatitis (AP). Reactive oxygen species induce activation of inflammatory cascades, inflammatory cell recruitment, and tissue damage. NF-κB regulates inflammatory cytokine gene expression, which induces an acute, edematous form of pancreatitis. Protein kinase C δ (PKCδ) activates NF-κB as shown in a mouse model of cerulein-induced AP. Docosahexaenoic acid (DHA), an ω-3 fatty acid, exerts anti-inflammatory and antioxidant effects in various cells and tissues. This study investigated whether DHA inhibits cerulein-induced AP in rats by assessing pancreatic edema, myeloperoxidase activity, levels of lipid peroxide and IL-6, activation of NF-κB and PKCδ, and by histologic observation. AP was induced by intraperitoneal injection (i.p.) of cerulein (50 μg/kg) every hour for 7 h. DHA (13 mg/kg) was administered i.p. for three days before AP induction. Pretreatment with DHA reduced cerulein-induced activation of NF-κB, PKCδ, and IL-6 in pancreatic tissues of rats. DHA suppressed pancreatic edema and decreased the abundance of lipid peroxide, myeloperoxidase activity, and inflammatory cell infiltration into the pancreatic tissues of cerulein-stimulated rats. Therefore, DHA may help prevent the development of pancreatitis by suppressing the activation of NF-κB and PKCδ, expression of IL-6, and oxidative damage to the pancreas. PMID:28704954

A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model

PubMed Central

Fujiwara, Norio; Som, Angel T.; Pham, Loc-Duyen D.; Lee, Brian J.; Mandeville, Emiri T.; Lo, Eng H.; Arai, Ken

2017-01-01

A free radical scavenger edaravone is clinically used in Japan for acute stroke, and several basic researches have carefully examined the mechanisms of edaravone's protective effects. However, its actions on pro-inflammatory responses under stroke are still understudied. In this study, we subjected adult male Sprague-Dawley rats to 90-min middle cerebral artery (MCA) occlusion followed by reperfusion. Edaravone was treated twice via tail vein; after MCA occlusion and after reperfusion. As expected, edaravone-treated group showed less infarct volume and edema formation compared with control group at 24-hour after ischemic onset. Furthermore, edaravone reduced the levels of plasma interleukin (IL)-1β and matrix metalloproteinase-9 at 3-hour after ischemic onset. Several molecules besides IL-1β and MMP-9 are involved in inflammatory responses under stroke conditions. Therefore, we also examined whether edaravone treatment could decrease a wide range of pro-inflammatory cytokines/chemokines by testing rat plasma samples with a rat cytokine array. MCAO rats showed elevations in plasma levels of CINC-1, Fractalkine, IL-1α, IL-1ra, IL-6, IL-10, IP-10, MIG, MIP-1α, and MIP-3α, and all these increases were reduced by edaravone treatment. These data suggest that free radical scavengers may reduce systemic inflammatory responses under acute stroke conditions, and therefore, oxidative stress can be still a viable target for acute stroke therapy. PMID:27589890

Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin.

PubMed

Recio, María-Carmen; Cerdá-Nicolás, Miguel; Potterat, Olivier; Hamburger, Matthias; Ríos, José-Luis

2006-05-01

The effects of a supercritical CO2 (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED50 values of 78 mg/kg and 165 mg/kg P. O., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62% and 32% oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37% and 33% reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The DCM extract inhibited oedema formation and neutrophil infiltration in subchronic inflammation in mice induced by repeated application of TPA. The extract showed activity after oral and topical administration by reducing the various parameters of the inflammatory response. The DCM extract (1 mg/ear) inhibited the delayed-type hypersensitivity (DTH) reaction induced by application of dinitrofluorobenzene (DNFB) after topical application. The response during the induction phase (24 h) was decreased by 48%, and the inflammatory phase (48 to 96 h) was reduced by 53 to 56%. The extract had no effect in this model when administered orally. The DCM extract (200 mg/kg P. O.) inhibited the acetic acid-induced writhing by 49%.

Acute lymphocytic cholangitis and liver failure in an Amur tiger (Panthera tigris altaica).

PubMed

Crook, Erika K; Carpenter, Nancy A

2014-03-01

An adult male Amur tiger (Panthera tigris altaica) with confirmed inflammatory bowel disease developed acute severe icterus, bilirubinuria, bilirubinemia, and elevated bile acids after a diet change. Liver biopsies showed moderate lymphoplasmacytic cholangiohepatitis (lymphocytic cholangitis). The tiger developed neurologic signs including ataxia, tremors, and seizures, as well as epistaxis. Therapy consisted of antibiotics, a steroid anti-inflammatory, vitamins, pro-coagulants, and liver-supportive medicines. The tiger improved from acute liver failure within 3 wk, while the epistaxis began at 3.5 wk and did not resolve until 10.5 wk. The long-term maintenance plan consists of oral prednisolone, metronidazole, ursodiol, and an all muscle-meat beef diet.

Evidence for Anti-Inflammatory Effects of Exercise in CKD

PubMed Central

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

2014-01-01

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

Design of novel potent antihyperlipidemic agents with antioxidant/anti-inflammatory properties: exploiting phenothiazine's strong antioxidant activity.

PubMed

Matralis, Alexios N; Kourounakis, Angeliki P

2014-03-27

Because atherosclerosis is an inflammatory process involving a series of pathological events such as dyslipidemia, oxidative stress, and blood clotting mechanisms, we hereby report the synthesis and evaluation of novel compounds in which antioxidant, anti-inflammatory, and squalene synthase (SQS) inhibitory/hypolipidemic activities are combined in simple molecules through design. The coupling of two different pharmacophores afforded compounds 1-12, whose biological profile was markedly improved compared to those of parent lead structures (i.e., the hypolipidemic 2-hydroxy-2-aryl-(benzo)oxa(or thia)zine and the antioxidant phenothiazine). Most derivatives strongly inhibited in vitro microsomal lipid and LDL peroxidation, exhibiting potent free-radical scavenging activity. They further significantly inhibited SQS activity and showed remarkable antidyslipidemic activity in vivo in animal models of acute and high-fat-induced hyperlipidemia. Finally, several compounds showed anti-inflammatory activity in vitro, inhibiting cycloxygenase (COX-1/2) activity. The multimodal properties of the new compounds and especially their combined antioxidant/SQS/COX inhibitory activity render them interesting lead compounds for further evaluation against atherosclerosis.

Anti-inflammatory activity of Elaeagnus angustifolia fruit extract on rat paw edema.

PubMed

Motevalian, Manijeh; Shiri, Mehdi; Shiri, Saeedeh; Shiri, Zahra; Shiri, Hadi

2017-07-26

The Elaeagnus angustifolia fruit has been traditionally used in Iranian herbal medicine to treat diarrhea and rheumatoid arthritis. In the present study, the effects of E. angustifolia fruit extract on the acute and chronic phases of formalin-induced rat paw edema were examined. The acute and chronic anti-inflammatory effects of E. angustifolia fruit extract were investigated through the subcutaneous injection of 100 μL of formalin (2.5%) into a rat's hind paw. Thirty minutes before the procedure, the experimental groups were treated intraperitoneally with hydroalcoholic fruit extracts of E. angustifolia (concentrations of 100, 300, 700, and 1000 mg/kg); sodium salicylate (SS, 400 mg/kg) and distilled water were used as positive and negative control groups, respectively. Treatment with SS and the fruit extracts were performed daily for 8 days, and the degree of edema was measured by using mercury plethysmometer and digital caliper. In the acute anti-inflammatory study, the extract showed a significant anti-inflammatory effect in a dose-dependent manner. The results of 1000 mg/kg of the extract was significantly different compared with the negative control group (p<0.05) and was comparable to sodium salicylate (p<0.05). Results from the chronic study suggested that E. angustifolia extract significantly reduced paw edema and inflammation in a dose-dependent manner. The results also showed that the measurement by digital caliper and mercury plethysmometer were both reliable and might be applied interchangeably (p<0.01). Phytochemical tests indicated that the hydroalcoholic fruit extract of E. angustifolia was positive for cardiac glycosides, flavonoids, terpenoids, and saponins. Based on our findings, the E. angustifolia fruit extract probably has acute and chronic anti-inflammatory activities to support its applications in folk medicine.

Inflammatory Milieu and Cardiovascular Homeostasis in Children With Obstructive Sleep Apnea.

PubMed

Smith, David F; Hossain, Md M; Hura, Arjan; Huang, Guixia; McConnell, Keith; Ishman, Stacey L; Amin, Raouf S

2017-04-01

Biomarkers of atherosclerosis (pro-inflammatory cytokines and acute phase reactants) are elevated in children with obstructive sleep apnea (OSA). However, their association with cardiovascular endpoints in children are not understood. We hypothesized that biomarkers of atherosclerosis in children with OSA correlate with pulse transit time (PTT), a surrogate measure of vascular stiffness, with some positively influencing and others negatively influencing PTT. Children with OSA and matched controls were recruited to the study. Pro-inflammatory cytokines and acute phase reactants were measured at 6:00 pm and 6:00 am. Polysomnography with beat-to-beat blood pressure was performed. PTT during wakefulness and stage 2 sleep was calculated. Diurnal variation of biomarkers and their associations with PTT was estimated. Factor analysis was used to determine the effect of groups of cytokines on PTT. One hundred fifty-five children participated in the study; 90 were healthy controls and 65 had OSA. Children with OSA exhibited a different diurnal variation of biomarkers than healthy controls, with pro-inflammatory cytokines peaking in the morning and acute phase reactants peaking in the afternoon. Structural equation modeling demonstrated that interleukins 6 and 8, tumor necrosis factor-α, and sCD40L had a shortening effect, while serum amyloid A, C-reactive protein, and adiponectin had a prolonging effect on PTT. As a result, there was no difference in PTT between the two groups. The differential relationships of acute phase reactants and pro-inflammatory cytokines with PTT suggest that in children with OSA, these mediators may have opposing actions to maintain cardiovascular homeostasis. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness.

PubMed

Marcella, J J; Ursell, P C; Goldberger, M; Lovejoy, W; Fenoglio, J J; Weiss, M B

1983-08-01

Kawasaki syndrome, an acute systemic inflammatory illness of unknown origin usually affecting children, may develop into a serious illness complicated by coronary artery aneurysms or myocarditis. This report describes an adult with Kawasaki syndrome studied by right ventricular endomyocardial biopsy and cardiac catheterization during the acute and recovery phases of illness. The initial biopsy specimen showed acute myocarditis and was associated with hemodynamic evidence of biventricular dysfunction, a severely depressed left ventricular ejection fraction and global hypokinesia. With time, there was spontaneous and rapid resolution of the inflammatory cell infiltrate with concurrent return to normal myocardial function. Right ventricular endomyocardial biopsy studies early in the course of the cardiac disease associated with Kawasaki syndrome may correlate with ventricular function and may be useful for monitoring immunosuppressive therapy in patients with this syndrome.

Analgesic Effect of Xenon in Rat Model of Inflammatory Pain.

PubMed

Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V

2017-02-01

The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.

Statin withdrawal: clinical implications and molecular mechanisms.

PubMed

Cubeddu, Luigi X; Seamon, Matthew J

2006-09-01

Retrospective analyses of data from the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM), the National Registry of Myocardial Infarction 4, and the Global Registry of Acute Coronary Events (GRACE) trials revealed that the benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on acute coronary outcomes are rapidly lost and outcomes worsened if statins are discontinued during a patient's hospitalization for an acute coronary syndrome. Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-elevation myocardial infarction increased the hospital morbidity and mortality rate versus continued therapy (11.9% vs 5.7%, p<0.01). Data from the Treating New Targets (TNT) study, however, suggested that short-term discontinuation of statin therapy in patients with stable cardiac conditions may not substantially increase the risk of acute coronary syndromes. In patients with acute coronary syndromes who discontinue statins, the rapid increase in risk of an event may result not only from the lost benefits from the therapy, but also from rebound inhibition of vascular protective substances and activation of vascular deleterious substances. Statins inhibit cholesterol synthesis in vascular cells. By reducing levels of isoprenoid intermediates, statins increase the production of nitric oxide and downregulate angiotensin II AT(1) receptors, endothelin-1, vascular inflammatory adhesion molecules, and inflammatory cytokines. These benefits are rapidly lost and often transiently reversed when statins are acutely discontinued. Acute removal of pleiotropic effects and rebound vascular dysfunction may be more important in an acute coronary event, where inflammation promotes rupture of atherosclerotic plaques and inflammatory and prothrombosis markers are present in high concentration, than in stable chronic vascular disease. In the absence of data from randomized controlled trials, current information suggests that statin therapy should be continued, and possibly boosted, during hospitalization for an acute coronary syndrome. Because statins are discontinued during the early hospitalization of many patients, practitioners must ensure that statins are not omitted, unless contraindicated, from the treatment of patients with acute coronary syndromes.

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

PubMed

Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status.

PubMed

Huang, Xianfeng; Liu, Yuanyuan; Lu, Yingxun; Ma, Chunhua

2015-05-01

Acute lung injury (ALI) represents a clinical syndrome that results from complex responses of the lung to a multitude of direct and indirect insults. This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings suggest that the protective mechanism of EUL may be attributed partly to decreased production of proinflammatory cytokines through the regulating inflammation and redox status. The results support that use of EUL is beneficial in the treatment of ALI. Copyright © 2015 Elsevier B.V. All rights reserved.

Blocking NF-κB: an inflammatory issue.

PubMed

Rahman, Arshad; Fazal, Fabeha

2011-11-01

The nuclear factor (NF)-κB is considered the master regulator of inflammatory responses. Studies in mouse models have established this transcription factor as an important mediator of many inflammatory disease states, including pulmonary diseases such as acute lung injury and acute respiratory distress syndrome. Endothelial cells provide the first barrier for leukocytes migrating to the inflamed sites and hence offer an attractive cellular context for targeting NF-κB for treatment of these diseases. However, recent studies showing that NF-κB also plays an important role in resolution phase of inflammation and in tissue repair and homeostasis have challenged the view of therapeutic inhibition of NF-κB. This article reviews the regulation of NF-κB in the context of endothelial cell signaling and provides a perspective on why "dampening" rather than "abolishing" NF-κB activation may be a safe and effective treatment strategy for inflammation-associated pulmonary and other inflammatory diseases.

Propagation prevention: a complementary mechanism for "lung protective" ventilation in acute respiratory distress syndrome.

PubMed

Marini, John J; Gattinoni, Luciano

2008-12-01

To describe the clinical implications of an often neglected mechanism through which localized acute lung injury may be propagated and intensified. Experimental and clinical evidence from the medical literature relevant to the airway propagation hypothesis and its consequences. The diffuse injury that characterizes acute respiratory distress syndrome is often considered a process that begins synchronously throughout the lung, mediated by inhaled or blood-borne noxious agents. Relatively little attention has been paid to possibility that inflammatory lung injury may also begin focally and propagate sequentially via the airway network, proceeding mouth-ward from distal to proximal. Were this true, modifications of ventilatory pattern and position aimed at geographic containment of the injury process could help prevent its generalization and limit disease severity. The purposes of this communication are to call attention to this seldom considered mechanism for extending lung injury that might further justify implementation of low tidal volume/high positive end-expiratory pressure ventilatory strategies for lung protection and to suggest additional therapeutic measures implied by this broadened conceptual paradigm.

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids.

PubMed

Jonasson, Sofia; Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders

2013-09-01

Chlorine (Cl2) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl2-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200ppm Cl2 during 15min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24h or 14days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100mg/kg) was administered intraperitoneally 1, 3, 6, or 12h following Cl2 exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1h was dose-dependent; high-dose significantly reduced acute airway inflammation (100mg/kg) but not treatment with the relatively low-dose (10mg/kg). Both doses reduced AHR 14days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl2 exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl2 exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

Emergence of new-onset psychotic disorder following recovery from LGI1 antibody-associated limbic encephalitis

PubMed Central

Moran, Nick

2017-01-01

Neuronal autoantibodies targeting cell surface antigens have been described in association with autoimmune encephalitides which frequently feature psychosis and other psychiatric disturbances alongside neurological signs and symptoms. Little has been written however about the long-term psychiatric status of individuals following recovery from the acute phase of autoimmune encephalitis, despite case series and anecdotal evidence suggesting this may be a cause of considerable disability. Here, we describe a man aged 58 years with no psychiatric history who developed a severe and acute psychotic disorder following resolution of a protracted course of limbic encephalitis associated with antibodies to leucine-rich glioma inactivated 1 protein. No indications of a gross ongoing inflammatory or encephalopathic process were present at presentation of his psychosis. Possible aetiologies of his acute psychosis are discussed. This case highlights the importance of ongoing psychiatric follow-up of patients following an episode of autoimmune encephalitis. PMID:28363946

Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders.

PubMed

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2018-06-08

Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth. Inflammatory factors stimulate the recruitment, expansion, and activation of MDSCs in tumors and inflamed tissues. The immunosuppression generated by MDSCs has an important role in the resolution of acute inflammation but in chronic inflammatory disorders, the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors, chronic infections, and many degenerative diseases. Currently, MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases. Interestingly, there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine. We will briefly describe the immune suppressive functions of MDSCs in cancers and age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories, e.g. flavonoids, terpenoids, retinoids, curcumins, and β-glucans, which possess the MDSC-dependent antitumor and anti-inflammatory properties. Copyright © 2018 Elsevier B.V. All rights reserved.

Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice.

PubMed

Shigemori, Suguru; Watanabe, Takafumi; Kudoh, Kai; Ihara, Masaki; Nigar, Shireen; Yamamoto, Yoshinari; Suda, Yoshihito; Sato, Takashi; Kitazawa, Haruki; Shimosato, Takeshi

2015-11-25

Mucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy. We developed a strain of gmLAB, Lactococcus lactis NZ9000 (NZ-HO), which secretes the anti-inflammatory molecule recombinant mouse heme oxygenase-1 (rmHO-1). The effects of short-term continuous oral dosing with NZ-HO were evaluated in mice with dextran sulfate sodium (DSS)-induced acute colitis as a model of inflammatory bowel diseases (IBD). We identified the secretion of rmHO-1 by NZ-HO. rmHO-1 was biologically active as determined with spectroscopy. Viable NZ-HO was directly delivered to the colon via oral administration, and rmHO-1 was secreted onto the colonic mucosa in mice. Acute colitis in mice was induced by free drinking of 3 % DSS in water and was accompanied by an increase in the disease activity index score and histopathological changes. Daily oral administration of NZ-HO significantly improved these colitis-associated symptoms. In addition, NZ-HO significantly increased production of the anti-inflammatory cytokine interleukin (IL)-10 and decreased the expression of pro-inflammatory cytokines such as IL-1α and IL-6 in the colon compared to a vector control strain. Oral administration of NZ-HO alleviates DSS-induced acute colitis in mice. Our results suggest that NZ-HO may be a useful mucosal therapeutic agent for treating IBD.

Fermented herbal formula KIOM-MA-128 protects against acute colitis induced by dextran sodium sulfate in mice.

PubMed

Kim, Dong-Gun; Lee, Mi-Ra; Yoo, Jae-Myung; Park, Kwang-Il; Ma, Jin-Yeul

2017-07-05

Colitis is a well-known subtype of inflammatory bowel disease and is caused by diverse factors. Previous research has shown that KIOM-MA elicits anti-inflammatory and anti-allergic effects on various diseases. KIOM-MA-128, our novel herbal formula, was generated from KIOM-MA using probiotics to improve the therapeutic efficacy. We investigated whether KIOM-MA-128 has protective activity in a mouse model of acute colitis induced by dextran sodium sulfate (DSS). Colitis was induced by DSS administered to ICR mice in drinking water. KIOM-MA-128 (125 or 250 mg/kg) was orally administered once per day. The body weights of the mice were measured daily, and colonic endoscopies were performed at 5 and 8 days. Colon length as well as histological and cytokine changes were observed at the end of drug administration. KIOM-MA-128 has pharmacological activity in an acute colitis model. KIOM-MA-128 reduced the loss of body weight and disease activity index (DAI) and inhibited the abnormally short colon lengths and the colonic damage in this mouse model of acute colitis. Moreover, KIOM-MA-128 suppressed pro-inflammatory cytokine expression and maintained the integrity of the tight junctions during DSS-induced colitis. The results indicated that KIOM-MA-128 protects against DSS-induced colitis in mice and suggested that this formula might be a candidate treatment for inflammatory bowel disease (IBD).

Allergic contact dermatitis from color film developers: clinical and histologic features.

PubMed

Brancaccio, R R; Cockerell, C J; Belsito, D; Ostreicher, R

1993-05-01

We evaluated two patients with allergic contact dermatitis that resulted from exposure to color film developers. A lichenoid eruption developed in one patient, whereas an eruption more characteristic of an acute spongiotic dermatitis developed in the second patient. Histologic findings in the first case were those of a "lichenoid dermatitis" but with features distinct from classic lichen planus. The biopsy specimens from the second patient showed a subacute spongiotic process with a bandlike infiltrate suggestive of an evolving lichenoid process. Contact allergy to color developers may result in eruptions similar to lichen planus. This process appears to evolve from an acute spongiotic dermatitis in its early phase to a lichenoid dermatitis in fully developed and more chronic forms. Although the histologic features are those of a "lichenoid" dermatitis, some features, such as the presence of spongiosis, eosinophils, and a less intense inflammatory infiltrate, may enable distinction between lichenoid allergic contact dermatitis and true lichen planus. In addition, clinicopathologic correlation with patch test results should permit accurate diagnosis in most cases.

Aged red garlic extract reduces lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages and acute pulmonary inflammation through haeme oxygenase-1 induction.

PubMed

Park, H-J; Jeon, B T; Kim, H C; Roh, G S; Shin, J-H; Sung, N-J; Han, J; Kang, D

2012-05-01

It is known that garlic has antioxidative and anti-inflammatory properties. Aged red garlic (ARG), a novel aged garlic formulation, has higher antioxidant effects than fresh raw garlic. This study was performed to examine the anti-inflammatory effects of ARG extract (ARGE). The anti-inflammatory effects of ARGE were evaluated in the lipopolysaccharide (LPS)-treated Raw 264.7 macrophages and acute lung inflammatory mice. NO production was determined by the Griess method, and iNOS, HO-1 and COX-2 expressions were measured using Western blot analysis. Histology and inflammation extent of lung were analysed using haematoxylin-eosin staining and immunohistochemistry. ARGE treatment markedly reduced LPS-induced nitrite production in RAW 264.7 macrophages and reduced inducible nitric oxide synthase (iNOS) expression. Treatment of cells with ARGE led to a significant increase in haeme oxygenase-1 (HO-1) protein expression, which was mediated by stimulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Treatment with zinc protoporphyrin, a selective inhibitor of HO-1, significantly reversed the ARGE-mediated inhibition of nitrite production (P < 0.05). In LPS-induced inflammatory mice, ARGE treatment down-regulated iNOS and COX-2 expressions, while it up-regulated HO-1 expression. These results show that ARGE reduces LPS-induced nitric oxide production in RAW 264.7 macrophages through HO-1 induction and suggest that ARGE may have potential effects on prevention and treatment of acute inflammatory lung injury. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

MAR binding protein SMAR1 favors IL-10 mediated regulatory T cell function in acute colitis

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

Mirlekar, Bhalchandra; Patil, Sachin; Bopanna, Ramanamurthy

2015-08-21

T{sub reg} cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by T{sub reg} cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of T{sub reg} phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic T{sub reg} cells and is required for their ability to accumulate at inflammatory site and to sustain high levels ofmore » Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing T{sub reg} cells in SMAR1{sup −/−} mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic T{sub reg} cells that controls acute colitis. This data highlights a critical role of SMAR1 in maintaining T{sub reg} physiology during inflammatory disorders. - Highlights: • SMAR1 is essential to sustain high level of Foxp3 and IL-10 in T{sub reg} cells. • SMAR1{sup −/−} T{sub reg} cells produce pro-inflammatory cytokine IL-17 leads to inflammation. • IL-10 administration can control the inflammation in SMAR1{sup −/−} mice. • Both Foxp3 and SMAR1 maintain T{sub reg} phenotype that controls colitis.« less

Diagnosis and treatment of bacterial prostatitis.

PubMed

Videčnik Zorman, Jerneja; Matičič, Mojca; Jeverica, Samo; Smrkolj, Tomaž

2015-01-01

Prostate inflammation is a common syndrome, especially in men under 50. It usually presents with voiding symptoms and pain in the genitourinary area, and sometimes as sexual dysfunction. Based on clinical and laboratory characteristics, prostatitis is classified as acute bacterial prostatitis, chronic bacterial prostatitis, chronic inflammatory and non-inflammatory prostatitis or chronic pelvic pain syndrome, and asymptomatic inflammatory prostatitis. Bacterial prostatitis is most often caused by infection with uropathogens, mainly Gram-negative bacilli, but Gram-positive and atypical microorganisms have also been identified as causative organisms of chronic prostatitis. According to reports by several authors, Chlamydia trachomatis and Trichomonas vaginalis are some of the most common pathogens, making chronic prostatitis a sexually transmitted disease. Diagnosis and treatment of acute and chronic bacterial prostatitis in particular can be challenging.

Mitochondrial MnSOD mRNA expression in human chorioamniotic membranes and its association with labor, inflammation and infection

PubMed Central

Than, Nandor Gabor; Romero, Roberto; Tarca, Adi L.; Draghici, Sorin; Erez, Offer; Chaiworapongsa, Tinnakorn; Kim, Yeon Mee; Kim, Sun Kwon; Vaisbuch, Edi; Tromp, Gerard

2010-01-01

Objective Human parturition is characterized by the activation of genes involved in acute inflammatory in the fetal membranes. Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that scavenges reactive oxygen species (ROS). MnSOD is up-regulated in sites of inflammation and has an important role in the down-regulation of acute inflammatory processes. Therefore, the aim of this study was to determine the differences in MnSOD mRNA expression in the fetal membranes in patients with term and preterm labor as well as in acute chorioamnionitis. Study design Fetal membranes were obtained from patients in the following groups: 1) term not in labor (n=29); 2) term in labor (n=29); 3) spontaneous preterm labor with intact mebranes (n=16); 4) PTL with histological chorioamnionitis (n=12); 5) preterm prelabor rupture of membranes (PPROM; n=17); and 6) PPROM with histological chorioamnionitis (n=21). MnSOD mRNA expression in the membranes was determined by quantitative real-time RT-PCR. Results 1) MnSOD mRNA expression was higher in the fetal membranes of patients at term in labor than those not in labor (2.4-fold; p=0.02); 2) the amount of MnSOD mRNA in the fetal membranes was higher in PTL than in term labor or in PPROM (7.2-fold, p=0.03; 3.2-fold, p=0.03, respectively); 3) MnSOD mRNA expression was higher when histological chorioamnionitis was present both among patients with PPROM (3.8-fold, p=0.02) and with PTL (5.4-fold, p=0.02) than in patients with these conditions without histological chorioamnionitis; 4) expression of MnSOD mRNA was higher in PTL with chorioamnionitis than in PPROM with chorioamnionitis (4.3-fold, p=0.03); Conclusion The increase in MnSOD mRNA expression by fetal membranes in term labor and in histological chorioamnionitis in PTL and PPROM suggests that the fetus deploys anti-oxidant mechanisms to constrain the inflammatory processes in the chorioamniotic membranes. PMID:19900038

[The effect of an inflammatory reaction on the resistance of mice to infection by Listeria monocytogenes and Salmonella typhimurium].

PubMed

Fauve, R M; Hevin, B

1975-12-22

Following subcutaneous acute inflammatory reactions in mice, the blood clearance of virulent Salmonella typhimurium was enhanced and the multiplication of Listeria monocytogenes in spleen and liver was decreased.

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

2017-11-01

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 protein 72 analysis did not disclose any diagnosis or mortality group differences regarding either rs6457452 or rs1061581 haplotypes. Sepsis presents with similar profiles in adult and pediatric patients, characterized by enhanced inflammatory hormonal response and by repressed innate immunity, metabolism, and myocardial contractility. These features early distinguish sepsis from systemic inflammatory response syndrome across all age groups.

[HLA-B27 Positive Acute Anterior Uveitis - A Translational Perspective].

PubMed

Heiligenhaus, Arnd; Kasper, Maren; Grajewski, Rafael

2017-05-01

Background HLA-B27 positive acute anterior uveitis is the most common type of uveitis, and it is an autoimmune disease that can be triggered by infections. The precise mechanism of the interaction between involved microbes (mostly gram negative bacteria) and the host immune system is not clear. The disease probably results from an imbalance between pro- and anti-inflammatory components. Project description This article gives a compact overview about the current knowledge of the clinic and the etiopathogenesis of acute anterior uveitis as a basis for future research approaches. The goal of the current research is to classify the cellular and molecular pathogenetic factors in acute anterior uveitis. In this regard, a project on uveitis within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye", examines the hypothesis that dysregulation of regulatory cell populations and anti-inflammatory cytokines, such as interleukin-10 (IL-10), might contribute to the development of ocular autoimmunity following infections. The goal is to establish new markers for individual susceptibility in the risk group of the HLA-B27 positive population, because only about 1% of the HLA-B27 positive population will eventually develop acute anterior uveitis. Conclusions Translational research approaches to identify predisposed risk groups from the HLA-B27 population could improve patient care both on a prophylactic and a therapeutic level. Georg Thieme Verlag KG Stuttgart · New York.

Hydroxysafflor yellow A suppress oleic acid-induced acute lung injury via protein kinase A

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

Wang, Chaoyun; Huang, Qingxian; Wang, Chunhua

Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO{sub 2}), carbon dioxide tension, pH, and themore » PaO{sub 2}/fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22{sup phox} levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI. - Highlights: • Oleic acid (OA) cause acute lung injury (ALI) via inhibiting cAMP/PKA signal pathway. • Blocking protein kinase A (PKA) activation may enhance Cytokine release, increase NADPH oxidase activation and reduce activities of antioxidant enzymes. • Hydroxysafflor yellow A (HSYA) up regulate cAMP/PKA signal pathway in lung tissue induced by OA. • HSYA attenuate OA mediated lung injury via reducing inflammatory cytokine release and improving antioxidant capacity.« less

Neutrophil Extracellular Traps and Fibrin in Otitis Media: Analysis of Human and Chinchilla Temporal Bones.

PubMed

Schachern, Patricia A; Kwon, Geeyoun; Briles, David E; Ferrieri, Patricia; Juhn, Steven; Cureoglu, Sebahattin; Paparella, Michael M; Tsuprun, Vladimir

2017-10-01

Bacterial resistance in acute otitis can result in bacterial persistence and biofilm formation, triggering chronic and recurrent infections. To investigate the middle ear inflammatory response to bacterial infection in human and chinchilla temporal bones. Six chinchillas underwent intrabullar inoculations with 0.5 mL of 106 colony-forming units (CFUs) of Streptococcus pneumoniae, serotype 2. Two days later, we counted bacteria in middle ear effusions postmortem. One ear from each chinchilla was processed in paraffin and sectioned at 5 µm. The opposite ear was embedded in epoxy resin, sectioned at a thickness of 1 µm, and stained with toluidine blue. In addition, we examined human temporal bones from 2 deceased donors with clinical histories of otitis media (1 with acute onset otitis media, 1 with recurrent infection). Temporal bones had been previously removed at autopsy, processed, embedded in celloidin, and cut at a thickness of 20 µm. Sections of temporal bones from both chinchillas and humans were stained with hematoxylin-eosin and immunolabeled with antifibrin and antihistone H4 antibodies. Histopatological and imminohistochemical changes owing to otitis media. Bacterial counts in chinchilla middle ear effusions 2 days after inoculation were approximately 2 logs above initial inoculum counts. Both human and chinchilla middle ear effusions contained bacteria embedded in a fibrous matrix. Some fibers in the matrix showed positive staining with antifibrin antibody, others with antihistone H4 antibody. In acute and recurrent otitis media, fibrin and neutrophil extracellular traps (NETs) are part of the host inflammatory response to bacterial infection. In the early stages of otitis media the host defense system uses fibrin to entrap bacteria, and NETs function to eliminate bacteria. In chronic otitis media, fibrin and NETs appear to persist.

A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy.

PubMed

Chinen, Naofumi; Koyama, Yasushi; Sato, Shinji; Suzuki, Yasuo

2016-01-01

A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy.

Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats.

PubMed

Zhang, Hong-Bo; Sun, Li-Chao; Zhi, Li-da; Wen, Qian-Kuan; Qi, Zhi-Wei; Yan, Sheng-Tao; Li, Wen; Zhang, Guo-Qiang

2017-10-01

Sepsis is a systemic inflammatory response syndrome caused by severe infections. Astilbin is a dihydroflavonol derivative found in many medicinal and food plants with multiple pharmacological functions. To investigate the effects of astilbin on sepsis-induced acute lung injury (ALI), cecal ligation and puncture was performed on rats to establish a sepsis-induced ALI model; these rats were then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration were determined to evaluate the effects of astilbin on sepsis-induced ALI. We found that astilbin treatment significantly attenuates sepsis-induced lung injury and improves survival rate, lung injury scores, lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration. Astilbin treatment also dramatically decreased the production of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression and production of macrophage inhibitory factor (MIF), which inhibits the inflammatory response. Collectively, these data suggest that astilbin has a protective effect against sepsis-induced ALI by inhibiting MIF-mediated inflammatory responses. This study provides a molecular basis for astilbin as a new medical treatment for sepsis-induced ALI.

The Surgically Induced Stress Response

PubMed Central

Finnerty, Celeste C.; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A.; Herndon, David N.

2013-01-01

The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes which induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Although the stress response to acute trauma evolved to improve chances of survival following injury, in modern surgical practice the stress response can be detrimental. PMID:24009246

Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection: A case report.

PubMed

Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

2016-12-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. We report a case of acute-onset CIDP that was initially diagnosed as GBS. A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered.

Rehabilitation of a marathon runner with Guillain-Barré syndrome.

PubMed

Fisher, Tara Beth; Stevens, Jennifer E

2008-12-01

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy that affects nerve roots and peripheral nerves leading to motor neuropathy and flaccid paralysis. This case report describes the physical therapy examination, intervention, and outcomes for a marathon runner with GBS. The patient was a 30-year-old male marathon runner who presented with acutely evolving motor and sensory deficits that initially stabilized and then worsened. Both GBS and chronic inflammatory demyelinating polyradiculoneuropathy were considered as diagnoses, and medical treatment included a combination of intravenous administration of immunoglobulins, plasmapheresis, and corticosteroids. During his stay in an acute inpatient rehabilitation facility, the intervention was focused on regaining functional independence and strength with care not to induce fatigue or relapse. After three weeks in an acute inpatient rehabilitation facility, the patient showed marked gains in Functional Independence Measure scores and muscle performance as measured by manual muscle testing.

Acute urinary retention due to benign inflammatory nervous diseases.

PubMed

Sakakibara, Ryuji; Yamanishi, Tomonori; Uchiyama, Tomoyuki; Hattori, Takamichi

2006-08-01

Both neurologists and urologists might encounter patients with acute urinary retention due to benign inflammatory nervous diseases. Based on the mechanism of urinary retention, these disorders can be divided into two subgroups: disorders of the peripheral nervous system (e.g., sacral herpes) or the central nervous system (e.g., meningitis-retention syndrome [MRS]). Laboratory abnormalities include increased herpes virus titers in sacral herpes, and increased myelin basic protein in the cerebrospinal fluid (CSF) in some cases with MRS. Urodynamic abnormality in both conditions is detrusor areflexia; the putative mechanism of it is direct involvement of the pelvic nerves in sacral herpes; and acute spinal shock in MRS. There are few cases with CSF abnormality alone. Although these cases have a benign course, management of the acute urinary retention is necessary to avoid bladder injury due to overdistension. Clinical features of sacral herpes or MRS differ markedly from those of the original "Elsberg syndrome" cases.

Glucocorticoid exposure alters the pathogenesis of Theiler’s murine encephalomyelitis virus during acute infection

PubMed Central

Young, Erin E.; Prentice, Thomas W.; Satterlee, Danielle; McCullough, Heath; Sieve, Amy N.; Johnson, Robin R.; Welsh, Thomas H.; Welsh, C. Jane R.; Meagher, Mary W.

2008-01-01

Previous research has shown that chronic restraint stress exacerbates Theiler’s virus infection, a murine model for CNS inflammation and multiple sclerosis. The current set of experiments was designed to evaluate the potential role of glucocorticoids in the deleterious effects of restraint stress on acute CNS inflammatory disease. Exposure to chronic restraint stress resulted in elevated levels of corticosterone as well as increased clinical scores and weight loss (Experiment 1). In addition, corticosterone administration alone exacerbated behavioral signs of TMEV-induced sickness (i.e. decreased body weight, increased symptoms of encephalitis, and increased mortality) and reduced inflammation in the CNS (Experiment 2). Infected subjects receiving exogenous corticosterone showed exacerbation of acute phase measures of sickness and severe mortality as well as decreased viral clearance from CNS (Experiment 3). These findings indicate that corticosterone exposure alone is sufficient to exacerbate acute CNS inflammatory disease. PMID:18538803

[Prevention of acute purulent inflammatory diseases of the fingers and hand with decamethoxine].

PubMed

Kravets, V P

1992-01-01

Resulting from disease-prevention work among population of the district, use of BF-6D glue for treatment of microtraumas to skin of the hands, the number of patients with inflammatory diseases reduced by 14.7%.

Crohn's disease: management in adults, children and young people - concise guidance .

PubMed

Tun, Gloria Sz; Cripps, Sarah; Lobo, Alan J

2018-06-01

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. Individuals with CD present with acute inflammatory exacerbations as well as acute and chronic complications. Management requires specialist input from gastroenterologists, colorectal surgeons, nurse specialists and pharmacists as well as general and primary care physicians to allow appropriate selection of treatment options including surgery and rapid assessment and treatment of those with acute exacerbations. Monitoring of the individual and their medication is crucial in preventing and recognising complications including those associated with treatment. This concise guideline focuses on recommendations from National Institute for Health and Care Excellence (NICE) -Clinical -Guideline 152 (CG152) considered of key importance for implementation. © Royal College of Physicians 2018. All rights reserved.

Inhibition of 2-AG hydrolysis differentially regulates blood brain barrier permeability after injury.

PubMed

Piro, Justin R; Suidan, Georgette L; Quan, Jie; Pi, YeQing; O'Neill, Sharon M; Ilardi, Marissa; Pozdnyakov, Nikolay; Lanz, Thomas A; Xi, Hualin; Bell, Robert D; Samad, Tarek A

2018-05-14

Acute neurological insults caused by infection, systemic inflammation, ischemia, or traumatic injury are often associated with breakdown of the blood-brain barrier (BBB) followed by infiltration of peripheral immune cells, cytotoxic proteins, and water. BBB breakdown and extravasation of these peripheral components into the brain parenchyma result in inflammation, oxidative stress, edema, excitotoxicity, and neurodegeneration. These downstream consequences of BBB dysfunction can drive pathophysiological processes and play a substantial role in the morbidity and mortality of acute and chronic neurological insults, and contribute to long-term sequelae. Preserving or rescuing BBB integrity and homeostasis therefore represents a translational research area of high therapeutic potential. Induction of general and localized BBB disruption in mice was carried out using systemic administration of LPS and focal photothrombotic ischemic insult, respectively, in the presence and absence of the monoacylglycerol lipase (MAGL) inhibitor, CPD-4645. The effects of CPD-4645 treatment were assessed by gene expression analysis performed on neurovascular-enriched brain fractions, cytokine and inflammatory mediator measurement, and functional assessment of BBB permeability. The mechanism of action of CPD-4645 was studied pharmacologically using inverse agonists/antagonists of the cannabinoid receptors CB1 and CB2. Here, we demonstrate that the neurovasculature exhibits a unique transcriptional signature following inflammatory insults, and pharmacological inhibition of MAGL using a newly characterized inhibitor rescues the transcriptional profile of brain vasculature and restores its functional homeostasis. This pronounced effect of MAGL inhibition on blood-brain barrier permeability is evident following both systemic inflammatory and localized ischemic insults. Mechanistically, the protective effects of the MAGL inhibitor are partially mediated by cannabinoid receptor signaling in the ischemic brain insult. Our results support considering MAGL inhibitors as potential therapeutics for BBB dysfunction and cerebral edema associated with inflammatory brain insults.

Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse

PubMed Central

Rayes, Julie; Wichaiyo, Surasak; Haining, Elizabeth J.; Lowe, Kate; Grygielska, Beata; Laloo, Ryan; Flodby, Per; Borok, Zea; Crandall, Edward D.; Thickett, David R.; Watson, Steve P.

2017-01-01

There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (AECI)-specific or hematopoietic-specific podoplanin deficient, mice were established using cre-loxP strategies. Combining these with intratracheal (IT) instillations of lipopolysaccharide (LPS), we demonstrate that arterial oxygen saturation decline in response to IT-LPS in platelet-specific CLEC-2-deficient mice is significantly augmented. An increase in bronchoalveolar lavage (BAL) neutrophils and protein was also observed 48 h post-IT-LPS, with significant increases in pro-inflammatory chemokines detected in BAL of platelet-specific CLEC-2-deficient animals. Deletion of podoplanin from hematopoietic cells but not AECIs also reduces lung function and increases pro-inflammatory chemokine expression following IT-LPS. Furthermore, we demonstrate that following IT-LPS, platelets are present in BAL in aggregates with neutrophils, which allows for CLEC-2 interaction with podoplanin expressed on BAL inflammatory alveolar macrophages. Taken together, these data suggest that the platelet CLEC-2-podoplanin signaling axis regulates the severity of lung inflammation in mice and is a possible novel target for therapeutic intervention in patients at risk of developing ARDS. PMID:28839100

Inhibitory Effects of Emodin, Thymol, and Astragalin on Leptospira interrogans-Induced Inflammatory Response in the Uterine and Endometrium Epithelial Cells of Mice.

PubMed

Zhang, Wenlong; Lu, Xiaojie; Wang, Wei; Ding, Zhuang; Fu, Yunhe; Zhou, Xiaofei; Zhang, Naisheng; Cao, Yongguo

2017-04-01

Leptospirosis is a systemic infection that causes, among others, acute kidney injury, acute liver disease, muscle pain, vasculitis, bleeding disorders, and reproductive loss. In an effort to reduce uterine inflammatory responses induced by Leptospira, we evaluated the anti-inflammation effects of emodin, thymol, and astragalin in a mouse model. Our results showed that treatment with emodin, thymol, and astragalin alleviated uterine inflammation induced by leptospira infection via suppression of pro-inflammatory cytokine expression and prevented tissue damage. Furthermore, we used primary endometrium epithelial cells to show that treatment with these chemicals inhibited the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Western blot results showed that these chemicals suppressed the phosphorylation of p38, p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. These results indicate that treatment with emodin, thymol, and astragalin suppressed inflammatory response by regulating NF-κB and mitogen-activated protein kinase signaling pathways in leptospira-infected uterine and endometrium epithelial cells of mice.

RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury.

PubMed

Zhang, Zhuo; Zhou, Jie; Liao, Changli; Li, Xiaobing; Liu, Minghua; Song, Daqiang; Jiang, Xian

2017-04-01

Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.

Therapeutic effects of silibinin on LPS-induced acute lung injury by inhibiting NLRP3 and NF-κB signaling pathways.

PubMed

Tian, Lin; Li, Weimin; Wang, Tan

2017-07-01

Silibinin, a natural product extracted from Silybum marianum (milk thistle), has been reported to have anti-inflammatory effect. The aim of this study was to explore the therapeutic effects and potential mechanisms of silibinin on lipopolysaccharide (LPS)-stimulated inflammatory responses in acute lung injury (ALI). Male BALB/c mice were conditioned with silibinin 1 h after intranasal instillation of LPS. After 12 h, the myeloperoxidase (MPO) level in lung tissues, the wet/dry (W/D) ratio, inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), and histopathological examination of lung were detected. Our results showed that silibinin inhibited LPS-induced histopathological changes and MPO activity, as well as the wet/dry (W/D) ratio in the lung tissues. Furthermore, silibinin significantly inhibited LPS-induced inflammatory cytokines production in the BALF. In addition, silibinin suppressed LPS-induced NF-κB activation and the expression of NLRP3 inflammasome. These results indicate that silibinin exerts its anti-inflammatory effect by inhibiting NF-κB and NLRP3 signaling pathways. Copyright © 2017. Published by Elsevier Ltd.

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

PubMed Central

Almeida, Caroline de Souza; Andrade-Oliveira, Vinicius; Câmara, Niels Olsen Saraiva; Jacysyn, Jacqueline F.; Faquim-Mauro, Eliana L.

2015-01-01

Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a local anti-inflammatory profile in mice. PMID:25853847

Characterization of acute and long-term sulfur mustard-induced skin injuries in hairless guinea-pigs using non-invasive methods.

PubMed

Dachir, Shlomit; Cohen, Maayan; Fishbeine, Eliezer; Sahar, Rita; Brandies, Rachel; Horwitz, Vered; Kadar, Tamar

2010-02-01

Skin exposure to sulfur mustard (HD) results in erythema, edema and severe injury, which take long time to heal and might impose a heavy burden on the health system. Despite many years of research, there is no treatment that prevents the development of the cytotoxic effects of HD causing acute and prolonged damage to the skin. Therefore, it is of great importance to develop treatments that will ameliorate the extent of injury and improve as well as shorten the healing process. The aim of the present study was to establish a small animal model for a long-term HD-induced skin injury using the hairless guinea-pig (HGP) and to further test the efficacy of anti-inflammatories in ameliorating the pathology. HGPs were exposed to HD vapor on four sites for various time durations (1, 5, 10, 15 and 30 min). Clinical evaluation was conducted using reflectance colorimetry, transepidermal water loss and wound-area measurements. Biochemical [prostaglandin (PGE) content and metalloproteinase-9 (MMP-9) activity] and histopathological evaluations were conducted up to 2 weeks post-exposure. Typical symptoms of HD skin injury developed including erythema and edema and the extent of injury was closely related to the exposure duration. Histological evaluation revealed severe edema, infiltration of inflammatory cells, damage to basal cells and vesication. By 2 weeks, healing was not completed, impaired basement membrane and epithelial hyperplasia were observed. PGE content and MMP-9 activity increased at 2 h post-exposure; however, while PGE returned to baseline levels within 24 h, MMP-9 remained elevated at least up to 48 h. Furthermore, a short-term, topical, anti-inflammatory post-exposure treatment was effective in reducing the extent of the acute injury. These results indicate that the effects of HD on HGP skin are similar to previously shown effects in the pig model and in humans and therefore support the use of the HGP as an animal model for long-term effects of HD on skin injury and for studying the efficacy of anti-inflammatory treatments.

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice.

PubMed

Ramírez-Espinosa, Juan José; Saldaña-Ríos, Johann; García-Jiménez, Sara; Villalobos-Molina, Rafael; Ávila-Villarreal, Gabriela; Rodríguez-Ocampo, Angélica Nallelhy; Bernal-Fernández, Germán; Estrada-Soto, Samuel

2017-12-28

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice ( p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1β and TNF-α were diminished after 10 days' treatment compared with control group ( p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

PubMed

Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

2017-07-01

Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA 1c . Methods HbA 1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA 1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA 1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA 1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

The Role of Regulatory T Cell in Nontypeable Haemophilus influenzae-Induced Acute Exacerbation of Chronic Obstructive Pulmonary Disease

PubMed Central

Guan, Xuewa; Lu, Yanjiao; Wang, Guoqiang; Fang, Keyong; Wang, Ziyan; Pang, Zhiqiang; Guo, Yingqiao; Lu, Junying; Yuan, Yuze; Ran, Nan

2018-01-01

Chronic obstructive pulmonary disease (COPD) is associated with irreversible persistent airflow limitation and enhanced inflammation. The episodes of acute exacerbation (AECOPD) largely depend on the colonized pathogens such as nontypeable Haemophilus influenzae (NTHi), one of the most commonly isolated bacteria. Regulatory T cells (Tregs) are critical in controlling inflammatory immune responses and maintaining tolerance; however, their role in AECOPD is poorly understood. In this study, we hypothesized a regulatory role of Tregs, as NTHi participated in the progress of COPD. Immunological pathogenesis was investigated in a murine COPD model induced by cigarette smoke (CS). NTHi was administrated through intratracheal instillation for an acute exacerbation. Weight loss and lung function decline were observed in smoke-exposed mice. Mice in experimental groups exhibited serious inflammatory responses via histological and cytokine assessment. Expression levels of Tregs and Th17 cells with specific cytokines TGF-β1 and IL-17 were detected to assess the balance of pro-/anti-inflammatory influence partially. Our findings suggested an anti-inflammatory activity of Tregs in CS-induced model. But this activity was suppressed after NTHi administration. Collectively, these data suggested that NTHi might play a necessary role in downregulating Foxp3 to impair the function of Tregs, helping development into AECOPD. PMID:29725272

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits.

PubMed

Panchal, Shital S; Patidar, Rajesh K; Jha, Abhishek B; Allam, Ahmed A; Ajarem, Jamaan; Butani, Shital B

2017-01-01

Purpose . γ -Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods . Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF- α and IL-6. Structural damage in eye was examined by histopathological studies. Results . In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF- α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions . Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage.

Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study.

PubMed

Kaspar, Felix; Jelinek, Herbert F; Perkins, Steven; Al-Aubaidy, Hayder A; deJong, Bev; Butkowski, Eugene

2016-01-01

This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Cohort study with repeated-measures design. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (-20%; p = 0.047) and a decrease of MCP-1 (-17.9%; p = 0.03). This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population.

PubMed

Rajendran, Karthick; Devarajan, Nalini; Ganesan, Manohar; Ragunathan, Malathi

2012-08-14

Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD) including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI) patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product) is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6) and high sensitivity - C reactive protein (hs-CRP). Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling.

PubMed

Zhang, Wen-zhou; Jiang, Zheng-kui; He, Bao-xia; Liu, Xian-ben

2015-08-01

Arctigenin, a bioactive component of Arctium lappa (Nubang), has anti-inflammatory activity. Here, we investigated the effects of arctigenin on lipopolysaccharide (LPS)-induced acute lung injury. Mice were divided into four groups: control, LPS, LPS + DMSO, and LPS + Arctigenin. Mice in the LPS + Arctigenin group were injected intraperitoneally with 50 mg/kg of arctigenin 1 h before an intratracheal administration of LPS (5 mg/kg). Lung tissues and bronchoalveolar lavage fluids (BALFs) were collected. Histological changes of the lung were analyzed by hematoxylin and eosin staining. Arctigenin decreased LPS-induced acute lung inflammation, infiltration of inflammatory cells into BALF, and production of pro-inflammatory cytokines. Moreover, arctigenin pretreatment reduced the malondialdehyde level and increased superoxide dismutase and catalase activities and glutathione peroxidase/glutathione disulfide ratio in the lung. Mechanically, arctigenin significantly reduced the production of nitric oxygen and inducible nitric oxygen synthase (iNOS) expression, enhanced the expression of heme oxygenase-1, and decreased the phosphorylation of mitogen-activated protein kinases (MAPKs). Arctigenin has anti-inflammatory and antioxidative effects on LPS-induced acute lung injury, which are associated with modulation of MAPK, HO-1, and iNOS signaling.

A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model.

PubMed

Fujiwara, Norio; Som, Angel T; Pham, Loc-Duyen D; Lee, Brian J; Mandeville, Emiri T; Lo, Eng H; Arai, Ken

2016-10-28

A free radical scavenger edaravone is clinically used in Japan for acute stroke, and several basic researches have carefully examined the mechanisms of edaravone's protective effects. However, its actions on pro-inflammatory responses under stroke are still understudied. In this study, we subjected adult male Sprague-Dawley rats to 90-min middle cerebral artery (MCA) occlusion followed by reperfusion. Edaravone was treated twice via tail vein; after MCA occlusion and after reperfusion. As expected, edaravone-treated group showed less infarct volume and edema formation compared with control group at 24-h after an ischemic onset. Furthermore, edaravone reduced the levels of plasma interleukin (IL)-1β and matrix metalloproteinase-9 at 3-h after ischemic onset. Several molecules besides IL-1β and MMP-9 are involved in inflammatory responses under stroke conditions. Therefore, we also examined whether edaravone treatment could decrease a wide range of pro-inflammatory cytokines/chemokines by testing rat plasma samples with a rat cytokine array. MCAO rats showed elevations in plasma levels of CINC-1, Fractalkine, IL-1α, IL-1ra, IL-6, IL-10, IP-10, MIG, MIP-1α, and MIP-3α, and all these increases were reduced by edaravone treatment. These data suggest that free radical scavengers may reduce systemic inflammatory responses under acute stroke conditions, and therefore, oxidative stress can be still a viable target for acute stroke therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Jobelyn® exhibited anti-inflammatory, antioxidant, and membrane-stabilizing activities in experimental models.

PubMed

Umukoro, Solomon; Oluwole, Oluwafemi Gabriel; Eduviere, Anthony T; Adrian, Omogbiya Itievere; Ajayi, Abayomi M

2015-09-01

Jobelyn® (JB) is an African sorghum-based food supplement claimed to be efficacious for the treatment of rheumatoid arthritis (RA). Although in vitro studies confirmed its anti-inflammatory property, no study had shown the effect of JB using in vivo animal models of inflammation. Thus, its effects on acute and chronic inflammation in rats were evaluated in this study. Its effect on rat red blood cell (RBC) lysis was also assessed. Acute inflammation was induced with intraplanter injection of carrageenan and increase in rat paw volume was measured using plethysmometer. The volume of fluid exudates, number of leukocytes, concentrations of malondialdehyde (MDA), and glutathione (GSH) in the fluid were measured on day 5 after induction of chronic inflammation with carrageenan in the granuloma air pouch model. RBC lysis induced by hypotonic medium as determined by release of hemoglobin was measured spectrophotometerically. JB (50-200 mg/kg) given orally produced a significant inhibition of acute inflammation induced by carrageenan in rats. It reduced the volume and number of leukocytes in inflammatory fluid in the granuloma air pouch model of chronic inflammation. It further decreased the levels of MDA in the fluid suggesting antioxidant property. JB elevated the concentrations of GSH in inflammatory exudates indicating free radical scavenging activity. It also significantly inhibited RBC lysis caused by hypotonic medium, suggesting membrane-stabilizing property. JB has in vivo anti-inflammatory activity, which may be related to its antioxidant and membrane-stabilizing properties, supporting its use for the treatment of arthritic disorder.

NAD+-dependent sirtuin 1 and 6 proteins coordinate a switch from glucose to fatty acid oxidation during the acute inflammatory response.

PubMed

Liu, Tie Fu; Vachharajani, Vidula T; Yoza, Barbara K; McCall, Charles E

2012-07-27

The early initiation phase of acute inflammation is anabolic and primarily requires glycolysis with reduced mitochondrial glucose oxidation for energy, whereas the later adaptation phase is catabolic and primarily requires fatty acid oxidation for energy. We reported previously that switching from the early to the late acute inflammatory response following TLR4 stimulation depends on NAD(+) activation of deacetylase sirtuin 1 (SirT1). Here, we tested whether NAD(+) sensing by sirtuins couples metabolic polarity with the acute inflammatory response. We found in TLR4-stimulated THP-1 promonocytes that SirT1 and SirT 6 support a switch from increased glycolysis to increased fatty acid oxidation as early inflammation converts to late inflammation. Glycolysis enhancement required hypoxia-inducing factor-1α to up-regulate glucose transporter Glut1, phospho-fructose kinase, and pyruvate dehydrogenase kinase 1, which interrupted pyruvate dehydrogenase and reduced mitochondrial glucose oxidation. The shift to late acute inflammation and elevated fatty acid oxidation required peroxisome proliferator-activated receptor γ coactivators PGC-1α and β to increase external membrane CD36 and fatty acid mitochondrial transporter carnitine palmitoyl transferase 1. Metabolic coupling between early and late responses also required NAD(+) production from nicotinamide phosphoryltransferase (Nampt) and activation of SirT6 to reduce glycolysis and SirT1 to increase fatty oxidation. We confirmed similar shifts in metabolic polarity during the late immunosuppressed stage of human sepsis blood leukocytes and murine sepsis splenocytes. We conclude that NAD(+)-dependent bioenergy shifts link metabolism with the early and late stages of acute inflammation.

Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties.

PubMed

Nagao, Saori; Taguchi, Kazuaki; Sakai, Hiromi; Yamasaki, Keishi; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

Carbon monoxide (CO) has attracted attention as a possible therapeutic agent for affecting anti-inflammatory and antioxidant activities. Previously, CO-bound hemoglobin vesicle (CO-HbV) was developed as a nanotechnology-based CO donor, and its safety profile and therapeutic potential as a clinically applicable carrier of CO were examined in vitro and in vivo. In the present study, the therapeutic efficacy of CO-HbV against severe acute pancreatitis was examined with secondary distal organ-injured model mice that were fed with a choline-deficient ethionine-supplemented diet. A CO-HbV treatment significantly reduced the mortality of the acute pancreatitis model mice compared to saline and HbV. Biochemical and histological evaluations clearly showed that CO-HbV suppressed acute pancreatitis by inhibiting the production of systemic proinflammatory cytokines, neutrophil infiltration, and oxidative injuries in pancreatic tissue. Interestingly, CO-HbV also diminished the subsequent damage to distal organs including liver, kidneys, and lungs. This could be due to the suppression of neutrophil infiltration into tissues and the subsequently enhanced oxidative injuries. In contrast, O 2 -bound HbV, the inactive form of CO-HbV, was ineffective against both pancreatitis and distal organ injuries, confirming that CO was directly responsible for the protective effects of CO-HbV in acute pancreatitis. These findings suggest that CO-HbV has anti-inflammatory and antioxidant characteristics of CO and consequently exerts a superior protective effect against acute pancreatitis-induced multiorgan damage.

The investigation of anti-inflammatory activity of Yi Guanjian decoction by serum metabonomics approach.

PubMed

Shui, Sufang; Cai, Xiaorong; Huang, Rongqing; Xiao, Bingkun; Yang, Jianyun

2017-01-30

Yi Guanjian (YGJ), one of the Chinese herbal medicines most commonly used in western countries, reported to possess significant anti-inflammatary effects that inhibit the process of inflammation. However, the mechanisms underlying its anti-inflammation effects remain largely unresolved. This study was aimed to investigate the anti-inflammatory activity of YGJ and to explore its potential anti-inflammatory mechanisms by serum metabonomics approach. An xylene-induced mouse right-ear-edema model was used as an inflammatory response in vivo model. Ear edema, prostaglandin E2 (PGE 2 ) and Tumor-Necrosis-Factor-alpha (TNF-α) were detected. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after YGJ administration and further integration of metabolic networks. The results showed that YGJ alleviated ear edema and decreased serum PGE 2 and TNF-α levels. Fourteen biomarkers were screened, and the levels were all reversed to different degrees after YGJ administration. These biomarkers were mainly related to linoleic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism and citrate cycle (TCA cycle). In metabolic networks, glycine and pyruvate were node molecules. This indicated that YGJ could significantly inhibit inflammatory response triggered by acute local stimulation and exerted anti-inflammatory activity mainly by regulating node molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With Low Back Pain and the Effects of Spinal Manipulation: A Nonrandomized Clinical Trial.

PubMed

Teodorczyk-Injeyan, Julita A; McGregor, Marion; Triano, John J; Injeyan, Stephen H

2018-01-01

The involvement of inflammatory components in the pathophysiology of low back pain (LBP) is poorly understood. It has been suggested that spinal manipulative therapy (SMT) may exert anti-inflammatory effects. The purpose of this study was to determine the involvement of inflammation-associated chemokines (CC series) in the pathogenesis of nonspecific LBP and to evaluate the effect of SMT on that process. Patients presenting with nonradicular, nonspecific LBP (minimum pain score 3 on 10-point visual analog scale) were recruited according to stringent inclusion criteria. They were evaluated for appropriateness to treat using a high velocity low amplitude manipulative thrust in the lumbar-lumbosacral region. Blood samples were obtained at baseline and following the administration of a series of 6 high velocity low amplitude manipulative thrusts on alternate days over the period of 2 weeks. The in vitro levels of CC chemokine ligands (CCL2, CCL3, and CCL4) production and plasma levels of an inflammatory biomarker, soluble E-selectin (sE-selectin), were determined at baseline and at the termination of treatments 2 weeks later. Compared with asymptomatic controls baseline production of all chemokines was significantly elevated in acute (P=0.004 to <0.0001), and that of CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production was significantly higher (P<0.0001) in the acute versus chronic LBP group. sE-selectin levels were significantly higher (P=0.003) in chronic but not in acute LBP patients. Following SMT, patient-reported outcomes showed significant (P<0.0001) improvements in visual analog scale and Oswestry Disability Index scores. This was accompanied by a significant decline in CCL3 production (P<0.0001) in both groups of patients. Change scores for CCL4 production differed significantly (P<0.0001) only for the acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin levels was noted in either group. The production of chemotactic cytokines is significantly and protractedly elevated in LBP patients. Changes in chemokine production levels, which might be related to SMT, differ in the acute and chronic LBP patient cohorts.

Acute ileitis facilitates infection with multidrug resistant Pseudomonas aeruginosa in human microbiota-associated mice.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa has become a serious issue in prevention of its spread particularly among hospitalized patients. It is, however, unclear whether distinct conditions such as acute intestinal inflammation facilitate P. aeruginosa infection of vertebrate hosts. To address this, we analysed P. aeruginosa infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral Toxoplasma gondii challenge. When perorally infected with P. aeruginosa at day 3 post ileitis induction, hma mice displayed higher intestinal P. aeruginosa loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by P. aeruginosa (except for lowered bifidobacterial populations), and the infection did not further enhance ileal immune cell responses. Pro-inflammatory cytokines including IFN-γ and IL-12p70 were similarly increased in ileum and mesenteric lymph nodes of P. aeruginosa infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in P. aeruginosa infected as compared to uninfected controls. Immune responses were not restricted to the intestines as indicated by elevated pro-inflammatory cytokine levels in liver and kidney upon ileitis induction. However, except for hepatic TNF-α levels, P. aeruginosa infection did not result in more distinct pro-inflammatory cytokine secretion in liver and kidney of hma mice with ileitis. Whereas viable intestinal bacteria were more frequently detected in systemic compartments such as spleen and cardiac blood of P. aeruginosa infected than uninfected mice at day 7 following ileitis induction, P. aeruginosa infection did not exacerbate systemic pro-inflammatory sequelae, but resulted in lower IL-10 serum levels. Acute intestinal inflammation facilitates infection of the vertebrate host with MDR bacteria including P. aeruginosa and might also pose particularly hospitalized patients at risk for acquisition. Since acute T. gondii induced inflammation might mask immunopathology caused by P. aeruginosa , a subacute or chronic inflammation model might be better suited to investigate the potential role of P. aeruginosa infection in the aggravation of intestinal disease.

Acute and chronic rejection: compartmentalization and kinetics of counterbalancing signals in cardiac transplants.

PubMed

Kaul, A M K; Goparaju, S; Dvorina, N; Iida, S; Keslar, K S; de la Motte, C A; Valujskikh, A; Fairchild, R L; Baldwin, W M

2015-02-01

Acute and chronic rejection impact distinct compartments of cardiac allografts. Intramyocardial mononuclear cell infiltrates define acute rejection, whereas chronic rejection affects large arteries. Hearts transplanted from male to female C57BL/6 mice undergo acute rejection with interstitial infiltrates at 2 weeks that resolve by 6 weeks when large arteries develop arteriopathy. These processes are dependent on T cells because no infiltrates developed in T cell-deficient mice and transfer of CD4 T cells restored T cell as well as macrophage infiltrates and ultimately neointima formation. Markers of inflammatory macrophages were up-regulated in the interstitium acutely and decreased as markers of wound healing macrophages increased chronically. Programmed cell death protein, a negative costimulator, and its ligand PDL1 were up-regulated in the interstitium during resolution of acute rejection. Blocking PDL1:PD1 interactions in the acute phase increased interstitial T cell infiltrates. Toll-like receptor (TLR) 4 and its endogenous ligand hyaluronan were increased in arteries with neointimal expansion. Injection of hyaluronan fragments increased intragraft production of chemokines. Our data indicate that negative costimulatory pathways are critical for the resolution of acute interstitial infiltrates. In the arterial compartment recognition of endogenous ligands including hyaluronan by the innate TLRs may support the progression of arteriopathy. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Evolutionary medicine and chronic inflammatory state--known and new concepts in pathophysiology.

PubMed

Straub, Rainer H

2012-05-01

During the last 10 years, a series of exciting observations has led to a new theory of pathophysiology using insights from evolutionary biology and neuroendocrine immunology to understand the sequelae of chronic inflammatory disease. According to this theory, disease sequelae can be explained based on redirection of energy-rich fuels from storage organs to the activated immune system. These disease sequelae are highly diverse and include the following: sickness behavior, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, increase of adipose tissue near inflamed tissue, alterations of steroid hormone axes, elevated sympathetic tone and local sympathetic nerve fiber loss, decreased parasympathetic tone, hypertension, inflammation-related anemia, and osteopenia. Since these disease sequelae can be found in many animal models of chronic inflammatory diseases with mammals (e.g., monkeys, mice, rats, rabbits, etc.), the evolutionary time line goes back at least 70 million years. While the initial version of this theory could explain prominent sequelae of chronic inflammatory disease, it did not however address two features important in the pathogenesis of immune-mediated diseases: the time point when an acute inflammatory disease becomes chronic, and the appearance of hypertension in chronic inflammation. To address these aspects more specifically, a new version of the theory has been developed. This version defines more precisely the moment of transition from acute inflammatory disease to chronic inflammatory disease as a time in which energy stores become empty (complete energy consumption). Depending on the amount of stored energy, this time point can be calculated to be 19-43 days. Second, the revised theory addresses the mechanisms of essential hypertension since, on the basis of water loss, acute inflammatory diseases can stimulate water retention using a positively selected water retention system (identical to the energy provision system). In chronic smoldering inflammation, however, there is no increased water loss. In contrast, there is increased water generation in inflamed tissue and inflammatory cells, and the activation of the water retention system persists. This combination leads to a net increase of the systemic fluid volume, which is hypothesized to be the basis of essential hypertension (prevalence in adults 22-32%).

Cytokine levels (IL-4, IL-6, IL-8 and TGFβ) as potential biomarkers of systemic inflammatory response in trauma patients.

PubMed

Volpin, Gershon; Cohen, Miri; Assaf, Michael; Meir, Tamar; Katz, Rina; Pollack, Shimon

2014-06-01

Much research is now being conducted in order to understand the role of cytokines in the development of the inflammatory response following trauma. The purpose of this study was to evaluate whether serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma. We conducted a prospective study with 71 individuals of whom 13 (18.3 %) were healthy controls and 58 (81.7 %) were traumatized orthopaedic patients who were categorized into two groups: 31 (43.6 %) with moderate injuries and 27 (38.1 %) patients with severe orthopaedic trauma. Thirty cc of heparinized blood were drawn from each individual within a few hours after the injury. Serum levels of pro-inflammatory, regulatory and anti-inflammatory cytokines were measured in each individual participant. High levels of pro-inflammatory cytokines IL-1β,-6,-8,-12, tumour necrosis factor alpha and interferon gamma were found in all injured patients compared to healthy controls. Only IL-6 and IL-8 were significantly higher in the injured patients. Levels of the regulatory cytokines, transformed growth factor beta (TGF-β) and IL-10 were higher in the injured patients, but significant only for TGF-β. Levels of IL-4 were significantly lower in the injured groups as compared to the controls. Secretion of large amounts of pro-inflammatory cytokines and decreased level of anti-inflammatory cytokines during the acute phase of trauma may lead to the development of systemic inflammatory response syndrome (SIRS) in unstable polytraumatized patients. SIRS may result in life threatening conditions as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). High levels of IL-6, IL-8, TGFβ and low levels of IL-4 were found to be reliable markers for the existence of immune reactivity in trauma patients. More research is needed to study pattern of cytokine levels along the acute period of injury, after surgical interventions and during recovery.

Early Anti-inflammatory and Pro-angiogenic Myocardial Effects of Intravenous Serelaxin Infusion for 72 H in an Experimental Rat Model of Acute Myocardial Infarction.

PubMed

Sanchez-Mas, Jesus; Lax, Antonio; Asensio-Lopez, Mari C; Lencina, Miriam; Fernandez-Del Palacio, Maria J; Soriano-Filiu, Angela; de Boer, Rudolf A; Pascual-Figal, Domingo A

2017-12-01

Sprague Dawley rats were subjected to acute myocardial infarction (AMI) by permanent ligation of the left anterior descending coronary artery. At the time of AMI, a subcutaneous mini-osmotic pump was implanted and animals were randomized into three groups, according to the intravenous therapy received during the first 72 h: placebo-treated (saline), serelaxin10-treated (SRLX10 = 10 μg/kg/day), or serelaxin30-treated (SRLX30 = 30 μg/kg/day). Treatment with SRLX30 reduced the expression of inflammatory cytokines and chemokines, as well as the infiltration of macrophages, and increased the expression of pro-angiogenic markers and vessel density in the infarcted myocardium after 7 days. SRLX30 did not reduce early myocardial fibrosis but reduced myocardial levels of sST2 and galectin-3. No significant effects were observed with SRLX10 treatment. A significant correlation was observed between plasma levels of serelaxin and effect measures. The results suggest serelaxin has a protective effect in early processes of cardiac remodeling after AMI.

Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

PubMed Central

Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia

2017-01-01

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

PubMed Central

Leal, Ermelindo C.; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E.; Kokkotou, Efi; Mooney, David J.; LoGerfo, Frank W.; Pradhan-Nabzdyk, Leena; Veves, Aristidis

2016-01-01

Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. PMID:25871534

Impairment of VGLUT2 but not VGLUT1 signaling reduces neuropathy-induced hypersensitivity.

PubMed

Leo, Sandra; Moechars, Dieder; Callaerts-Vegh, Zsuzsanna; D'Hooge, Rudi; Meert, Theo

2009-11-01

Glutamate is the major excitatory neurotransmitter in the central nervous system with an important role in nociceptive processing. Storage of glutamate into vesicles is controlled by vesicular glutamate transporters (VGLUT). Null mutants for VGLUT1 and VGLUT2 were poorly viable, thus, pain-related behavior was presently compared between heterozygote VGLUT1 and VGLUT2 mice and their respective wild-type littermates using a test battery that included a variety of assays for thermal and mechanical acute nociception, and inflammatory and neuropathic pain syndromes. Behavioral analysis of VGLUT1 mutant mice did not show important behavioral changes in the pain conditions tested. Reduction of VGLUT2 also resulted in unaltered acute nociceptive and inflammatory-induced pain behavior. Interestingly, VGLUT2 heterozygote mice showed an attenuation or absence of some typical neuropathic pain features (e.g., absence of mechanical and cold allodynia after spared nerve injury). Chronic constriction injury in VGLUT2 heterozygote mice showed also reduced levels of cold allodynia, but had no impact on mechanical thresholds. Together, these data suggest that VGLUT2, but not VGLUT1, plays a role in neuropathy-induced allodynia and hypersensitivity, and might be a therapeutic target to prevent and/or treat neuropathic pain.

The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice.

PubMed

Chen, Tong; Mou, Yi; Tan, Jiani; Wei, Linlin; Qiao, Yixue; Wei, Tingting; Xiang, Pengjun; Peng, Sixun; Zhang, Yihua; Huang, Zhangjian; Ji, Hui

2015-03-01

CDDO-Me, initiated in a phase II clinical trial, is a potential useful therapeutic agent for cancer and inflammatory dysfunctions, whereas the therapeutic efficacy of CDDO-Me on LPS-induced acute lung injury (ALI) has not been reported as yet. The purpose of the present study was to explore the protective effect of CDDO-Me on LPS-induced ALI in mice and to investigate its possible mechanism. BalB/c mice received CDDO-Me (0.5mg/kg, 2mg/kg) or dexamethasone (5mg/kg) intraperitoneally 1h before LPS stimulation and were sacrificed 6h later. W/D ratio, lung MPO activity, number of total cells and neutrophils, pulmonary histopathology, IL-6, IL-1β, and TNF-α in the BALF were assessed. Furthermore, we estimated iNOS, IL-6, IL-1β, and TNF-α mRNA expression and NO production as well as the activation of the three main MAPKs, AkT, IκB-α and p65. Pretreatment with CDDO-Me significantly ameliorated W/D ratio, lung MPO activity, inflammatory cell infiltration, and inflammatory cytokine production in BALF from the in vivo study. Additionally, CDDO-Me had beneficial effects on the intervention for pathogenesis process at molecular, protein and transcriptional levels in vitro. These analytical results provided evidence that CDDO-Me could be a potential therapeutic candidate for treating LPS-induced ALI. Copyright © 2015 Elsevier B.V. All rights reserved.

Tocopherol Supplementation Reduces NO Production and Pulmonary Inflammatory Response to Bleomycin

PubMed Central

Shi, Jin Dong; Golden, Thea; Guo, Chang-Jiang; Tu, Shui Ping; Scott, Pamela; Lee, Mao-Jung; Yang, Chung S.; Gow, Andrew J.

2013-01-01

Bleomycin causes acute lung injury through production of reactive species and initiation of inflammation. Previous work has shown alteration to the production of reactive oxygen species results in attenuation of injury. Vitamin E, in particular, γ-tocopherol, isoform, has the potential to scavenge reactive oxygen and nitrogen species. This study examines the utility of dietary supplementation with tocopherols in reducing bleomycin-mediated acute lung injury. Male C57BL6/J mice were intratracheally instilled with PBS or 2 units/kg bleomycin. Animals were analyzed 3 and 8 days post instillation at the cellular, tissue, and organ levels. Results showed successful delivery of tocopherols to the lung via dietary supplementation. Also, increases in reactive oxygen and nitrogen species due to bleomycin are normalized in those mice fed tocopherol diet. Injury was not prevented but inflammation progression was altered, in particular macrophage activation and function. Inflammatory scores based on histology demonstrate limited progression of inflammation in those mice treated with bleomycin and fed tocopherol diet compared to control diet. Upregulation of enzymes and cytokines involved in pro-inflammation were limited by tocopherol supplementation. Day 3 functional changes in elastance in response to bleomycin are prevented, however, 8 days post injury the effect of the tocopherol diet is lost. The effect of tocopherol supplementation upon the inflammatory process is demonstrated by a shift in the phenotype of macrophage activation. The effect of these changes on resolution and the progression of pulmonary fibrosis has yet to be elucidated. PMID:23669183

Anti-Inflammatory Activity of Polysaccharide Fraction of Curcuma longa (NR-INF-02).

PubMed

Illuri, Ramanaiah; Bethapudi, Bharathi; Anandhakumar, Senthilkumar; Murugan, Sasikumar; Joseph, Joshua Allan; Mundkinajeddu, Deepak; Agarwal, Amit; Velusami, Chandrasekaran Chinampudur

2015-04-07

The aim of the study was to investigate the safety and anti-inflammatory effects of polysaccharide fraction (F1) of Curcuma longa (NR-INF-02) in classical rodent models of inflammation. F1 was evaluated for its acute oral toxicity and found to be safe upto 5000 mg/kg body weight in rats. The anti-inflammatory activity of F1 was evaluated in acute (carrageenan - induced paw edema; xylene - induced ear edema) and chronic (cotton pellet - induced granuloma) models of inflammation. The results of the study demonstrated that F1 significantly (p ≤ 0.05) inhibited carrageenan-induced paw edema at 1 h and 3 h at doses of 11.25, 22.5 and 45 mg/kg body weight in rats. Also, F1 at doses of 15.75, 31.5 and 63 mg/kg significantly inhibited the xylene induced ear edema in mice. In a chronic model, F1 at 11.25, 22.5 and 45 mg/kg doses produced significant reduction of wet and dry weights of cotton pellets in rats. Overall results indicated that F1 of NR-INF-02 significantly attenuated acute and chronic inflammation in rodent models. This study emphasizes on the importance of Curcuma longa polysaccharide's role in acute and chronic inflammation.

Anti-Inflammatory Activity of Polysaccharide Fraction of Curcuma longa Extract (NR-INF-02).

PubMed

Illuri, Ramanaiah; Bethapudi, Bharathi; Anandakumar, Senthilkumar; Murugan, Sasikumar; Joseph, Joshua A; Mundkinajeddu, Deepak; Agarwal, Amit; Chandrasekaran, C V

2015-01-01

The aim of the study was to investigate the safety and anti-inflammatory effects of polysaccharide fraction (F1) of Curcuma longa extract (NR-INF-02) in classical rodent models of inflammation. F1 was evaluated for its acute oral toxicity and found to be safe upto 5000 mg/kg body weight in rats. The anti-inflammatory activity of F1 was evaluated in acute (carrageenan - induced paw edema; xylene - induced ear edema) and chronic (cotton pellet - induced granuloma) models of inflammation. The results of the study demonstrated that F1 significantly (p ≤ 0.05) inhibited carrageenan-induced paw edema at 1 h and 3 h at doses of 11.25, 22.5 and 45 mg/kg body weight in rats. Also, F1 at doses of 15.75, 31.5 and 63 mg/kg significantly inhibited the xylene induced ear edema in mice. In a chronic model, F1 at 11.25, 22.5 and 45 mg/kg doses produced significant reduction of wet and dry weights of cotton pellets in rats. Overall results indicated that F1 of NR-INF-02 significantly attenuated acute and chronic inflammation in rodent models. This study emphasizes on the importance of Curcuma longa polysaccharide's role in acute and chronic inflammation.

Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

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

Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr; Abdelmegeed, Mohamed A.; Song, Byoung-Joon, E-mail: bj.song@nih.gov

Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigatedmore » in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.« less

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw

PubMed Central

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-01-01

Background and purpose: α-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of α-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. Experimental approach: The biological activities of α-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-κB and up-regulated expression of kinin B1 receptors. Key results: Treatment with either α-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-κB induced by LPS in the rat paw. However, only α-humulene significantly reduced the increase in TNF-α and IL-1β levels, paw oedema and the up-regulation of B1 receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Conclusions and Implications: Both α-humulene and trans-caryophyllene inhibit the LPS-induced NF-κB activation and neutrophil migration, although only α-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-α and IL-1β and the in vivo up-regulation of kinin B1 receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes α-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases. PMID:17471174

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw.

PubMed

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-07-01

alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors. Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis

PubMed Central

Ramesh, Geeta; Borda, Juan T; Gill, Amy; Ribka, Erin P; Morici, Lisa A; Mottram, Peter; Martin, Dale S; Jacobs, Mary B; Didier, Peter J; Philipp, Mario T

2009-01-01

Background Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. Methods We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG). Results ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. Conclusion Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context. PMID:19706181

Anti-inflammatory effect of thalidomide alone or in combination with augmentin in Klebsiella pneumoniae B5055 induced acute lung infection in BALB/c mice.

PubMed

Kumar, Vijay; Chhibber, Sanjay

2008-09-11

Thalidomide (alpha-naphtylimidoglutarimide), a psychoactive drug that readily crosses blood-brain barrier, has been shown to exhibit anti-inflammatory, anti-angiogenic, immunomodulatory properties through a mechanism that is not fully established. Keeping these properties in mind, we tried to find out the anti-inflammatory properties of thalidomide in mouse model of acute inflammation by introducing K. pneumoniae B5055 in BALB/c mice via intranasal route. The intranasal instillation of bacteria in this mouse model of acute pneumonia induced inflammation accompanied with significant increase in neutrophil infiltration in the lungs and also increased production of mediators of inflammation (i.e. malondialdehyde, myeloperoxidase and nitric oxide) in the lung tissue. The animals, which received thalidomide alone orally or in combination with augmentin, 30 min prior to bacterial instillation into the lungs via intranasal route, showed significant (P<0.05) decrease in neutrophil influx into the lungs and there was significant (P<0.05) decrease in the production of malondialdehyde, nitric oxide and myeloperoxidase activity. But the augmentin treatment alone did not decrease the malondialdehyde, myeloperoxidase and nitric oxide significantly (P>0.05) as compared to the control group. We therefore conclude that thalidomide ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P<0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, it can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in case of acute lung infection.

Allergic rhinitis and inflammatory airway disease: interactions within the unified airspace.

PubMed

Marple, Bradley F

2010-01-01

Allergic rhinitis (AR), the most common chronic allergic condition in outpatient medicine, is associated with immense health care costs and socioeconomic consequences. AR's impact may be partly from interacting of respiratory conditions via allergic inflammation. This study was designed to review potential interactive mechanisms of AR and associated conditions and consider the relevance of a bidirectional "unified airway" respiratory inflammation model on diagnosis and treatment of inflammatory airway disease. MEDLINE was searched for pathophysiology and pathophysiological and epidemiologic links between AR and diseases of the sinuses, lungs, middle ear, and nasopharynx. Allergic-related inflammatory responses or neural and systemic processes fostering inflammatory changes distant from initial allergen provocation may link AR and comorbidities. Treating AR may benefit associated respiratory tract comorbidities. Besides improving AR outcomes, treatment inhibiting eosinophil recruitment and migration, normalizing cytokine profiles, and reducing asthma-associated health care use in atopic subjects would likely ameliorate other upper airway diseases such as acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis media with effusion. Epidemiological concordance of AR with several airway diseases conforms to a bidirectional "unified airway" respiratory inflammation model based on anatomic and histological upper and lower airway connections. Epidemiology and current understanding of inflammatory, humoral, and neural processes make links between AR and disorders including asthma, otitis media, NP, and CRS plausible. Combining AR with associated conditions increases disease burden; worsened associated illness may accompany worsened AR. AR pharmacotherapies include antihistamines, leukotriene antagonists, intranasal corticosteroids, and immunotherapy; treatments attenuating proinflammatory responses may also benefit associated conditions.

Endothelial Barrier Protection by Local Anesthetics: Ropivacaine and Lidocaine Block Tumor Necrosis Factor-α–induced Endothelial Cell Src Activation

PubMed Central

Piegeler, Tobias; Votta-Velis, E. Gina; Bakhshi, Farnaz R.; Mao, Mao; Carnegie, Graeme; Bonini, Marcelo G.; Schwartz, David E.; Borgeat, Alain; Beck-Schimmer, Beatrice; Minshall, Richard D.

2014-01-01

Background Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase–Akt–nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability. Methods Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed. Results Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10−10 M for ropivacaine; IC50 = 5.864 × 10−10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10−10 M for ropivacaine; IC50 = 6.377 × 10−10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated. Conclusions Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial cells by attenuating p85 recruitment to TNF-receptor-1. The resultant decrease in Akt, endothelial nitric oxide synthase, and Src phosphorylation reduced neutrophil adhesion and endothelial hyperpermeability. This novel anti-inflammatory “side-effect” of ropivacaine and lidocaine may provide therapeutic benefit in acute inflammatory disease. PMID:24525631

Endothelial barrier protection by local anesthetics: ropivacaine and lidocaine block tumor necrosis factor-α-induced endothelial cell Src activation.

PubMed

Piegeler, Tobias; Votta-Velis, E Gina; Bakhshi, Farnaz R; Mao, Mao; Carnegie, Graeme; Bonini, Marcelo G; Schwartz, David E; Borgeat, Alain; Beck-Schimmer, Beatrice; Minshall, Richard D

2014-06-01

Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase-Akt-nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability. Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed. Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10 M for ropivacaine; IC50 = 5.864 × 10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10 M for ropivacaine; IC50 = 6.377 × 10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated. Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial cells by attenuating p85 recruitment to TNF-receptor-1. The resultant decrease in Akt, endothelial nitric oxide synthase, and Src phosphorylation reduced neutrophil adhesion and endothelial hyperpermeability. This novel anti-inflammatory "side-effect" of ropivacaine and lidocaine may provide therapeutic benefit in acute inflammatory disease.

Computed tomography findings mimicking appendicitis as a manifestation of colorectal cancer☆

PubMed Central

Watchorn, Richard E.; Poder, Liina; Wang, Zhen J.; Yeh, Benjamin M.; Webb, Emily M.; Coakley, Fergus V.

2009-01-01

The primary computed tomography (CT) signs of appendicitis can also be seen with other inflammatory or neoplastic processes. We report on two cases in which appendiceal dilatation and peri-appendiceal fluid or stranding were the dominant imaging manifestations of colorectal carcinoma in the ascending colon. This study highlights the need to closely examine the ascending colon in patients with a suspected CT diagnosis of acute appendicitis, since these findings may be secondary to an inconspicuous colorectal carcinoma. PMID:19857802

NF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases.

PubMed

Lin, T-H; Pajarinen, J; Lu, L; Nabeshima, A; Cordova, L A; Yao, Z; Goodman, S B

Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a critical step for proper bone-healing and bone-remodeling processes. On the other hand, chronic inflammation with excessive proinflammatory cytokines disrupts the balance of skeletal homeostasis involving osteoblastic (bone formation) and osteoclastic (bone resorption) activities. NF-κB is a transcriptional factor that regulates the inflammatory response and bone-remodeling processes in both bone-forming and bone-resorption cells. In vitro and in vivo evidences suggest that NF-κB is an important potential therapeutic target for inflammation-associated bone disorders by modulating inflammation and bone-remodeling process simultaneously. The challenges of NF-κB-targeting therapy in bone disorders include: (1) the complexity of canonical and noncanonical NF-κB pathways; (2) the fundamental roles of NF-κB-mediated signaling for bone regeneration at earlier phases of tissue damage and acute inflammation; and (3) the potential toxic effects on nontargeted cells such as lymphocytes. Recent developments of novel inhibitors with differential approaches to modulate NF-κB activity, and the controlled release (local) or bone-targeting drug delivery (systemic) strategies, have largely increased the translational application of NF-κB therapy in bone disorders. Taken together, temporal modulation of NF-κB pathways with the combination of recent advanced bone-targeting drug delivery techniques is a highly translational strategy to reestablish homeostasis in the skeletal system. © 2017 Elsevier Inc. All rights reserved.

NF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases

PubMed Central

Lin, T.-h.; Pajarinen, J.; Lu, L.; Nabeshima, A.; Cordova, L.A.; Yao, Z.; Goodman, S.B.

2017-01-01

Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a critical step for proper bone-healing and bone-remodeling processes. On the other hand, chronic inflammation with excessive proinflammatory cytokines disrupts the balance of skeletal homeostasis involving osteoblastic (bone formation) and osteoclastic (bone resorption) activities. NF-κB is a transcriptional factor that regulates the inflammatory response and bone-remodeling processes in both bone-forming and bone-resorption cells. In vitro and in vivo evidences suggest that NF-κB is an important potential therapeutic target for inflammation-associated bone disorders by modulating inflammation and bone-remodeling process simultaneously. The challenges of NF-κB-targeting therapy in bone disorders include: (1) the complexity of canonical and noncanonical NF-κB pathways; (2) the fundamental roles of NF-κB-mediated signaling for bone regeneration at earlier phases of tissue damage and acute inflammation; and (3) the potential toxic effects on nontargeted cells such as lymphocytes. Recent developments of novel inhibitors with differential approaches to modulate NF-κB activity, and the controlled release (local) or bone-targeting drug delivery (systemic) strategies, have largely increased the translational application of NF-κB therapy in bone disorders. Taken together, temporal modulation of NF-κB pathways with the combination of recent advanced bone-targeting drug delivery techniques is a highly translational strategy to reestablish homeostasis in the skeletal system. PMID:28215222

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

PubMed Central

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

2012-01-01

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

Effects of Ghrelin miRNA on Inflammation and Calcium Pathway in Pancreatic Acinar Cells of Acute Pancreatitis.

PubMed

Tang, Xiping; Tang, Guodu; Liang, Zhihai; Qin, Mengbin; Fang, Chunyun; Zhang, Luyi

The study investigated the effects of endogenous targeted inhibition of ghrelin gene on inflammation and calcium pathway in an in vitro pancreatic acinar cell model of acute pancreatitis. Lentiviral expression vector against ghrelin gene was constructed and transfected into AR42J cells. The mRNA and protein expression of each gene were detected by reverse transcription polymerase chain reaction, Western blotting, or enzyme-linked immunosorbent assay. The concentration of intracellular calcium ([Ca]i) was determined by calcium fluorescence mark probe combined with laser scanning confocal microscopy. Compared with the control group, cerulein could upregulate mRNA and protein expression of inflammatory factors, calcium pathway, ghrelin, and [Ca]i. mRNA and protein expression of inflammatory factors increased significantly in cells transfected with ghrelin miRNA compared with the other groups. Intracellular calcium and expression of some calcium pathway proteins decreased significantly in cells transfected with ghrelin miRNA compared with the other groups. Targeted inhibition of ghrelin gene in pancreatic acinar cells of acute pancreatitis can upregulate the expression of the intracellular inflammatory factors and alleviate the intracellular calcium overload.

The Nitrated Fatty Acid 10-Nitro-oleate Diminishes Severity of LPS-Induced Acute Lung Injury in Mice

PubMed Central

Reddy, Aravind T.; Lakshmi, Sowmya P.; Reddy, Raju C.

2012-01-01

Acute lung injury (ALI) is an inflammatory condition culminating in respiratory failure. There is currently no effective pharmacological treatment. Nitrated fatty acids (NFAs) have been shown to exert anti-inflammatory effects. We therefore hypothesized that delivery of NFAs directly to the site of inflammation would reduce the severity of ALI. Pulmonary delivery of 10-nitro-oleate following endotoxin-induced ALI in mice reduced markers of lung inflammation and injury, including capillary leakage, lung edema, infiltration of neutrophils into the lung, and oxidant stress, as well as plasma levels of proinflammatory cytokines. Nitro-oleate delivery likewise downregulated expression of proinflammatory genes by alveolar macrophages, key cells in regulation of lung inflammation. These effects may be accounted for by the observed increases in the activity of PPAR-γ and the PPAR-γ-induced antioxidant transcription factor Nrf2, together with the decreased activity of NF-κB. Our results demonstrate that pulmonary delivery of NFAs reduces severity of acute lung injury and suggest potential utility of these molecules in other inflammatory lung diseases. PMID:22919366

The role of the immune system in central nervous system plasticity after acute injury.

PubMed

Peruzzotti-Jametti, Luca; Donegá, Matteo; Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

2014-12-26

Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways.

PubMed

Jo, Il-Joo; Bae, Gi-Sang; Choi, Sun Bok; Kim, Dong-Goo; Shin, Joon-Yeon; Seo, Seung-Hee; Choi, Mee-Ok; Kim, Tae-Hyeon; Song, Ho-Joon; Park, Sung-Joo

2014-08-15

Acute pancreatitis (AP) is a complicated disease which is largely undiscovered. Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have anti-inflammatory, antioxidant, and anti-cancer activities in various disease models. However, the effects of fisetin on AP have not been determined. Pre- and post- treatment of mice with fisetin reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (pancreatic weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and production of inflammatory cytokines. In pancreatic acinar cells, fisetin also inhibited cell death and production of inflammatory cytokines. In addition, fisetin inhibited activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-κB in vivo and in vitro. In conclusion, these results suggest that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial agent in the treatment of AP and its pulmonary complications. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibition of plasmin attenuates murine acute graft-versus-host disease mortality by suppressing the matrix metalloproteinase-9-dependent inflammatory cytokine storm and effector cell trafficking.

PubMed

Sato, A; Nishida, C; Sato-Kusubata, K; Ishihara, M; Tashiro, Y; Gritli, I; Shimazu, H; Munakata, S; Yagita, H; Okumura, K; Tsuda, Y; Okada, Y; Tojo, A; Nakauchi, H; Takahashi, S; Heissig, B; Hattori, K

2015-01-01

The systemic inflammatory response observed during acute graft-versus-host disease (aGVHD) is driven by proinflammatory cytokines, a 'cytokine storm'. The function of plasmin in regulating the inflammatory response is not fully understood, and its role in the development of aGVHD remains unresolved. Here we show that plasmin is activated during the early phase of aGVHD in mice, and its activation correlated with aGVHD severity in humans. Pharmacological plasmin inhibition protected against aGVHD-associated lethality in mice. Mechanistically, plasmin inhibition impaired the infiltration of inflammatory cells, the release of membrane-associated proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and Fas-ligand directly, or indirectly via matrix metalloproteinases (MMPs) and alters monocyte chemoattractant protein-1 (MCP-1) signaling. We propose that plasmin and potentially MMP-9 inhibition offers a novel therapeutic strategy to control the deadly cytokine storm in patients with aGVHD, thereby preventing tissue destruction.

Anti-inflammatory activity of Ambrosia artemisiaefolia and Rhoeo spathacea.

PubMed

Pérez G, R M

1996-09-01

Alcoholic extracts of the leaves of Ambrosia artemisiaefolia and Rhoeo spathacea have been investigated for anti-inflammatory activity using various experimental models of inflammation (croton oil ear oedema, carrageenan-induced edema, cotton pellet granuloma and formaldehyde induced arthritis) and the results compared with phenylbutazone and bethamethasone, standard anti-inflammatory drugs. These extracts at doses of 50, 100 and 150mg/kg of A. artemisiaefolia and R. spathacea, showed significant inhibition of acute oedema in rats and mice induced by the phlogistic agents, carrageenan and croton oil, in a dose-dependant manner. The ethanol extracts reduced cotton pellet granuloma and caused a statistically significant inhibitory effect on edema in the chronic model of formaldehyde arthritis in rats. Since Ambrosia artemisiaefolia and Rhoeo spathacea were found to be effective in both acute and chronic phases of inflammation they can be considered as general anti-inflammatory agents. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Cellular and molecular interactions of mesenchymal stem cells in innate immunity.

PubMed

Spaggiari, Grazia Maria; Moretta, Lorenzo

2013-01-01

In recent years, human mesenchymal stem/stromal cells (MSC) have attracted major attention for their possible clinical applications. In addition to their tissue regenerative capacity, they display immune-modulatory properties for which they have been used in the treatment of acute graft-versus-host disease and autoimmune diseases. Various studies have analyzed the inhibitory effect exerted by MSC on cells belonging to acquired or to innate immunity. In this context, MSC have been shown to inhibit proliferation and function of natural killer (NK) cells and to hinder the generation of dendritic cells and macrophages, thus interfering with inflammatory processes and with the generation of type I immune responses. In addition, MSC promote the differentiation of regulatory cells and participate in the regeneration of tissues damaged as a consequence of the inflammatory process. Different molecular mechanisms are involved in the immunosuppressive effect. Further investigation on the biology of MSC and on the regulatory events involved in their functional activities can help to optimize their use in clinical practice.

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

PubMed

Yue, Rongzheng; Zuo, Chuan; Zeng, Jing; Su, Baihai; Tao, Ye; Huang, Songmin; Zeng, Rui

2017-11-01

To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p < .05) and ameliorated the contrast-induced acute kidney injury (p < .05) and significantly reduced Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (Myd88), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression and relative mRNA expression levels (p < .05) and significantly decreased expression levels of downstream inflammatory factors (p < .05). Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

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

Okunieff, Paul; Xu Jianhua; Hu Dongping

2006-07-01

Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to themore » hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.« less

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

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

Zhang, Da-Gang

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl{sub 4})-induced acute liver injury. Mice were intraperitoneally injected with CCl{sub 4} (0.15 ml/kg). In CCl{sub 4} + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl{sub 4}. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl{sub 4}-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatmentmore » inhibited CCl{sub 4}-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl{sub 4}-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl{sub 4}-induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl{sub 4}-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl{sub 4}-induced acute liver injury. These results suggest that OCA protects against CCl{sub 4}-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl{sub 4}-induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl{sub 4}-induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.« less

[Morphological changes of the intestine in experimental acute intestinal infection in the treatment of colloidal silver].

PubMed

Polov'ian, E S; Chemich, N D; Moskalenko, R A; Romaniuk, A N

2012-06-01

At the present stage of infectionist practice in the treatment of acute intestinal infections caused by opportunistic microorganisms, colloidal silver is used with a particle size of 25 nm as an alternative to conventional causal therapy. In 32 rats, distributed in 4 groups of 8 animals each (intact; healthy, got colloidal silver; with a modeled acute intestinal infection in the basic treatment and with the addition of colloidal silver), histological examination was performed of small and large intestine of rats. Oral administration of colloidal silver at a dose of 0.02 mg/day to intact rats did not lead to changes in morphometric parameters compared to the norm, and during early convalescence in rats with acute intestinal infections were observed destructive and compensatory changes in the intestine, which depended on the treatment regimen. With the introduction of colloidal silver decreased activity of the inflammatory process and the severity of morphological changes in tissues of small and large intestine, indicating that the positive effect of study drug compared with baseline therapy.

Comparison of active constituents, acute toxicity, anti-nociceptive and anti-inflammatory activities of Porana sinensis Hemsl., Erycibe obtusifolia Benth. and Erycibe schmidtii Craib.

PubMed

Chen, Zhiyong; Liao, Liping; Zhang, Zijia; Wu, Lihong; Wang, Zhengtao

2013-11-25

Erycibe obtusifolia and Erycibe schmidtii, which belong to the same genus as Erycibe, are widely used in traditional medicine for the treatment of joint pain and rheumatoid arthritis (RA). Porana sinensis has become a widely used substitute for Erycibe obtusifolia and Erycibe schmidtii as they have declined in the wild. In the present work, the content of the main active components, the acute toxicity, the anti-nociceptive and anti-inflammatory activities of Porana sinensis, Erycibe obtusifolia and Erycibe schmidtii were compared, and the mechanisms of anti-nociceptive and anti-inflammatory activities were discussed. A quantitative HPLC (high performance liquid chromatography) method was first developed to compare the content of the main active components (scopoletin, scopolin and chlorogenic acid). The anti-inflammatory and anti-nociceptive activities of 40% ethanolic extracts of the three plants were compared using the models of xylene-induced ear edema, formalin-induced inflammation, carrageenan-induced air pouch inflammation, acetic acid-induced writhing and formalin-induced nociception. The acute toxicity of the 40% ethanolic extracts of the three plants was studied. The assay suggested a large content of scopoletin, scopolin and chlorogenic acid in the three plants. The 40% ethanolic extracts of the three plants were almost non-toxic at the dose of 5g/kg and all of them showed significant anti-inflammatory effects in the tests of xylene-induced ear edema and formalin-induced inflammation. In the carrageenan-induced air pouch inflammation test, the synthesis of PGE2 was significantly inhibited by all the extracts. They significantly inhibited the number of contortions induced by acetic acid and the second phase of the formalin-induced licking response. Naloxone was not able to reverse the analgesic effect of these extracts. The study identifies the similarity of the three plants in their main active components as well as acute toxicity, anti-nociceptive and anti-inflammatory activities. It supports the use of Porana sinensis as a suitable substitute, but further studies are needed to confirm this. © 2013 Elsevier Ireland Ltd. All rights reserved.

Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice

PubMed Central

Grady, Eileen F; Yoshimi, Shandra K; Maa, John; Valeroso, Dahlia; Vartanian, Robert K; Rahim, Shamila; Kim, Edward H; Gerard, Craig; Gerard, Norma; Bunnett, Nigel W; Kirkwood, Kimberly S

2000-01-01

Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis.Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1-R agonists/antagonists in rats and NK1-R(+/+)/(−/−) mice. The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized.In rats, both SP and the NK1-R selective agonist [Sar9 Met(O2)11]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1-R antagonist CP 96,345. Selective agonists of the NK-2 or NK-3 receptors had no effect.In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1-R antagonist CP 96,345.In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1-R knockout mice.In NK1-R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals.Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis. PMID:10821777

Effects of acute systemic inflammation on the interplay between sad mood and affective cognition.

PubMed

Benson, Sven; Brinkhoff, Alexandra; Lueg, Larissa; Roderigo, Till; Kribben, Andreas; Wilde, Benjamin; Witzke, Oliver; Engler, Harald; Schedlowski, Manfred; Elsenbruch, Sigrid

2017-12-11

Experimental endotoxemia is a translational model to study inflammatory mechanisms involved in the pathophysiology of mood disorders including depression. Disturbed affective cognition constitutes a core aspect in depression, but has never been studied in the context of inflammation. We combined experimental endotoxemia with an established experimental mood induction procedure to assess the interaction between acute inflammation and sad mood and their effects on affective cognition. In this randomized cross-over study, N = 15 healthy males received endotoxin (0.8 ng/kg lipopolysaccharide iv) on one study day and placebo an otherwise identical study day. The affective Go/Nogo task was conducted after experimental induction of neutral and sad mood. Inflammatory markers were assessed hourly. Endotoxin application induced a transient systemic inflammation, characterized by increased leukocyte counts, TNF-alpha and interleukin-6 plasma concentrations (all p < 0.01, interaction effects). Mood induction led to greater sadness ratings, with highest ratings when sad mood was induced during inflammation (p < 0.05, interaction effect). Based on a 2 (endotoxin vs. placebo) × 2 (sad vs. neutral mood) × 2 (sad vs. happy Go/Nogo target words) factorial design, we observed a significant target × endotoxin condition interaction (p < 0.01) reflecting slower responses to sad targets during endotoxemia. Additionally, we found a valence × mood interaction (p < 0.05), reflecting slower reaction times to sad targets in sad mood. In summary, acute inflammation and sad mood are risk factors for disturbed affective cognition. The results may reflect a mood-congruency effect, with prolonged and sustained processing of mood-congruent information during acute inflammation, which may contribute to depression risk.

Hfe Deficiency Impairs Pulmonary Neutrophil Recruitment in Response to Inflammation

PubMed Central

Benesova, Karolina; Vujić Spasić, Maja; Schaefer, Sebastian M.; Stolte, Jens; Baehr-Ivacevic, Tomi; Waldow, Katharina; Zhou, Zhe; Klingmueller, Ursula; Benes, Vladimir; Mall, Marcus A.; Muckenthaler, Martina U.

2012-01-01

Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe−/− mice) affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe−/− and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS) and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe−/− mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe−/− and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis. PMID:22745741

Inflammation: friend or foe for animal production?

PubMed

Broom, Leon J; Kogut, Michael H

2018-02-01

Inflammation is an essential immune response that seeks to contain microbial infection and repair damaged tissue. Increased pro-inflammatory mediators have been associated with enhanced resistance to a range of important poultry and pig pathogens. However, inflammation may also have undesirable consequences, including potentially exacerbating tissue damage and diverting nutrients away from productive purposes. The negative effects of inflammation have led to the active pursuit of anti-inflammatory feed additives and/or strategies. These approaches may, however, impair the ability of an animal to respond appropriately and effectively to the array of pathogens that are likely to be encountered in commercial production, and specifically young animals who may be particularly reliant on innate immune responses. Thus, promoting an animal's capacity to mount a rapid, acute inflammatory response to control and contain the infection and the timely transition to anti-inflammatory, tissue repair processes, and a homeostatic state are suggested as the optimum scenario to maintain an animal's resistance to pathogens and minimize non-productive nutrient losses. Important future studies will help to unravel the trade-offs, and relevant metabolic pathways, between robust immune defense and optimum productive performance, and thus provide real insight into methods to appropriately influence this relationship. © 2017 Poultry Science Association Inc.

Removal of inflammatory ascites is associated with dynamic modification of local and systemic inflammation along with prevention of acute lung injury: in vivo and in silico studies.

PubMed

Emr, Bryanna; Sadowsky, David; Azhar, Nabil; Gatto, Louis A; An, Gary; Nieman, Gary F; Vodovotz, Yoram

2014-04-01

Sepsis-induced inflammation in the gut/peritoneal compartment occurs early in sepsis and can lead to acute lung injury (ALI). We have suggested that inflammatory ascites drives the pathogenesis of ALI and that removal of ascites with an abdominal wound vacuum prevents ALI. We hypothesized that the time- and compartment-dependent changes in inflammation that determine this process can be discerned using principal component analysis (PCA) and Dynamic Bayesian Network (DBN) inference. To test this hypothesis, data from a previous study were analyzed using PCA and DBN. In that study, two groups of anesthetized, ventilated pigs were subjected to experimental sepsis via intestinal ischemia/reperfusion and placement of a peritoneal fecal clot. The control group (n = 6) had the abdomen opened at 12 h after injury (T12) with attachment of a passive drain. The peritoneal suction treatment (PST) group (n = 6) was treated in an identical fashion except that a vacuum was applied to the peritoneal cavity at T12 to remove ascites and maintained until T48. Multiple inflammatory mediators were measured in ascites and plasma and related to lung function (PaO2/FIO2 ratio and oxygen index) using PCA and DBN. Peritoneal suction treatment prevented ALI based on lung histopathology, whereas control animals developed ALI. Principal component analysis revealed that local to the insult (i.e., ascites), primary proinflammatory cytokines play a decreased role in the overall response in the treatment group as compared with control. In both groups, multiple, nested positive feedback loops were inferred from DBN, which included interrelated roles for bacterial endotoxin, interleukin 6, transforming growth factor β1, C-reactive protein, PaO2/FIO2 ratio, and oxygen index. von Willebrand factor was an output in control, but not PST, ascites. These combined in vivo and in silico studies suggest that in this clinically realistic paradigm of sepsis, endotoxin drives the inflammatory response in the ascites, interplaying with lung dysfunction in a feed-forward loop that exacerbates inflammation and leads to endothelial dysfunction, systemic spillover, and ALI; PST partially modifies this process.

The PGC-1 coactivators promote an anti-inflammatory environment in skeletal muscle in vivo

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

Eisele, Petra Sabine; Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich; Furrer, Regula

The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is abundantly expressed in trained muscles and regulates muscle adaptation to endurance exercise. Inversely, mice lacking a functional PGC-1α allele in muscle exhibit reduced muscle functionality and increased inflammation. In isolated muscle cells, PGC-1α and the related PGC-1β counteract the induction of inflammation by reducing the activity of the nuclear factor κB (NFκB). We now tested the effects of these metabolic regulators on inflammatory reactions in muscle tissue of control and muscle-specific PGC-1α/-1β transgenic mice in vivo in the basal state as well as after an acute inflammatory insult. Surprisingly, we observed amore » PGC-1-dependent alteration of the cytokine profile characterized by an increase in anti-inflammatory factors and a strong suppression of the pro-inflammatory interleukin 12 (IL-12). In conclusion, the anti-inflammatory environment in muscle that is promoted by the PGC-1s might contribute to the beneficial effects of these coactivators on muscle function and provides a molecular link underlying the tight mutual regulation of metabolism and inflammation. - Highlights: • Muscle PGC-1s are insufficient to prevent acute systemic inflammation. • The muscle PGC-1s however promote a local anti-inflammatory environment. • This anti-inflammatory environment could contribute to the therapeutic effect of the PGC-1s.« less

Ibuprofen does not reverse ventilatory acclimatization to chronic hypoxia.

PubMed

De La Zerda, D J; Stokes, J A; Do, J; Go, A; Fu, Z; Powell, F L

2017-07-27

Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic ventilatory response that is blocked by non-steroidal anti-inflammatory drugs administered during sustained hypoxia. We tested the hypothesis that inflammatory signals are necessary to sustain ventilatory acclimatization to hypoxia once it is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH, [Formula: see text] =70Torr) for 11-12days and treated with ibuprofen or saline for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood gas responses to O 2 and CO 2 were not affected by ibuprofen after acclimatization had been established. Immunohistochemistry and image analysis showed acute (1h) hypoxia activated microglia in a medullary respiratory center (nucleus tractus solitarius, NTS) and this was blocked by ibuprofen administered from the beginning of hypoxic exposure. Microglia returned to the control state after 7days of CH and were not affected by ibuprofen administered for 2 more days of CH. In contrast, NTS astrocytes were activated by CH but not acute hypoxia and activation was not reversed by administering ibuprofen for the last 2days of CH. Hence, ibuprofen cannot reverse ventilatory acclimatization or astrocyte activation after they have been established by sustained hypoxia. The results are consistent with a model for microglia activation or other ibuprofen-sensitive processes being necessary for the induction but not maintenance of ventilatory acclimatization to hypoxia. Copyright © 2017 Elsevier B.V. All rights reserved.

The A2a adenosine receptor modulates the reinforcement efficacy and neurotoxicity of MDMA.

PubMed

Ruiz-Medina, Jessica; Ledent, Catherine; Carretón, Olga; Valverde, Olga

2011-04-01

Adenosine is an endogenous purine nucleoside that plays a neuromodulatory role in the central nervous system. A2a adenosine receptors have been involved in reward-related processes, inflammatory phenomena and neurotoxicity reactions. In the present study, we investigated the role of A2a adenosine receptors on the acute pharmacological effects, reinforcement and neuroinflammation induced by MDMA administration. First, the acute effects of MDMA on body temperature, locomotor activity and anxiety-like responses were measured in A2a knockout mice and wild-type littermates. Second, MDMA reinforcing properties were evaluated using the intravenous self-administration paradigm. Finally, we assessed striatal astrogliosis and microgliosis as markers of MDMA neurotoxicity. Our results showed that acute MDMA produced a biphasic effect on body temperature and increased locomotor activity and anxiogenic-like responses in both genotypes. However, MDMA reinforcing properties were dramatically affected by the lack of A2a adenosine receptors. Thus, wild-type mice maintained MDMA self-administration under a fixed ratio 1 reinforcement schedule, whereas the operant response appeared completely abolished in A2a knockout mice. In addition, the MDMA neurotoxic regime produced an enhanced inflammatory response in striatum of wild-type mice, revealed by a significant increase in glial expression, whereas such activation was attenuated in mutant mice. This is the first report indicating that A2a adenosine receptors play a key role in reinforcement and neuroinflammation induced by the widely used psychostimulant.

Biomarkers for the acute respiratory distress syndrome: how to make the diagnosis more precise

PubMed Central

García-Laorden, M. Isabel; Lorente, José A.; Flores, Carlos; Slutsky, Arthur S.

2017-01-01

The acute respiratory distress syndrome (ARDS) is an acute inflammatory process of the lung caused by a direct or indirect insult to the alveolar-capillary membrane. Currently, ARDS is diagnosed based on a combination of clinical and physiological variables. The lack of a specific biomarker for ARDS is arguably one of the most important obstacles to progress in developing novel treatments for ARDS. In this article, we will review the current understanding of some appealing biomarkers that have been measured in human blood, bronchoalveolar lavage fluid (BALF) or exhaled gas that could be used for identifying patients with ARDS, for enrolling ARDS patients into clinical trials, or for better monitoring of patient’s management. After a literature search, we identified several biomarkers that are associated with the highest sensitivity and specificity for the diagnosis or outcome prediction of ARDS: receptor for advanced glycation end-products (RAGE), angiopoietin-2 (Ang-2), surfactant protein D (SP-D), inteleukin-8, Fas and Fas ligand, procollagen peptide (PCP) I and III, octane, acetaldehyde, and 3-methylheptane. In general, these are cell-specific for epithelial or endothelial injury or involved in the inflammatory or infectious response. No biomarker or biomarkers have yet been confirmed for the diagnosis of ARDS or prediction of its prognosis. However, it is anticipated that in the near future, using biomarkers for defining ARDS, or for determining those patients who are more likely to benefit from a given therapy will have a major effect on clinical practice. PMID:28828358

Correlative mRNA and Protein Expression of Middle and Inner Ear Inflammatory Cytokines during Mouse Acute Otitis Media

PubMed Central

Trune, Dennis R.; Kempton, Beth; Hausman, Frances A.; Larrain, Barbara E.; MacArthur, Carol J.

2015-01-01

Although the inner ear has long been reported to be susceptible to middle ear disease, little is known of the inflammatory mechanisms that might cause permanent sensorineural hearing loss. Recent studies have shown inner ear tissues are capable of expressing inflammatory cytokines during otitis media. However, little quantitative information is available concerning cytokine gene expression in the inner ear and the protein products that result. Therefore, this study was conducted of mouse middle and inner ear during acute otitis media to measure the relationship between inflammatory cytokine genes and their protein products with quantitative RT-PCR and ELISA, respectively. Balb/c mice were inoculated transtympanically with heat-killed Haemophilus influenzae and middle and inner ear tissues collected for either quantitative RT-PCR microarrays or ELISA multiplex arrays. mRNA for several cytokine genes was significantly increased in both the middle and inner ear at 6 hours. In the inner ear, these included MIP-2 (448 fold), IL-6 (126 fold), IL-1β (7.8 fold), IL-10 (10.7 fold), TNFα (1.8 fold), and IL-1α (1.5 fold). The 24 hour samples showed a similar pattern of gene expression, although generally at lower levels. In parallel, the ELISA showed the related cytokines were present in the inner ear at concentrations higher by 2 to 122 fold higher at 18 hours, declining slightly from there at 24 hours. Immunohistochemistry with antibodies to a number of these cytokines demonstrated they occurred in greater amounts in the inner ear tissues. These findings demonstrate considerable inflammatory gene expression and gene products in the inner ear following acute otitis media. These higher cytokine levels suggest one potential mechanism for the permanent hearing loss seen in some cases of acute and chronic otitis media. PMID:25922207

Correlative mRNA and protein expression of middle and inner ear inflammatory cytokines during mouse acute otitis media.

PubMed

Trune, Dennis R; Kempton, Beth; Hausman, Frances A; Larrain, Barbara E; MacArthur, Carol J

2015-08-01

Although the inner ear has long been reported to be susceptible to middle ear disease, little is known of the inflammatory mechanisms that might cause permanent sensorineural hearing loss. Recent studies have shown inner ear tissues are capable of expressing inflammatory cytokines during otitis media. However, little quantitative information is available concerning cytokine gene expression in the inner ear and the protein products that result. Therefore, this study was conducted of mouse middle and inner ear during acute otitis media to measure the relationship between inflammatory cytokine genes and their protein products with quantitative RT-PCR and ELISA, respectively. Balb/c mice were inoculated transtympanically with heat-killed Haemophilus influenzae and middle and inner ear tissues collected for either quantitative RT-PCR microarrays or ELISA multiplex arrays. mRNA for several cytokine genes was significantly increased in both the middle and inner ear at 6 h. In the inner ear, these included MIP-2 (448 fold), IL-6 (126 fold), IL-1β (7.8 fold), IL-10 (10.7 fold), TNFα (1.8 fold), and IL-1α (1.5 fold). The 24 h samples showed a similar pattern of gene expression, although generally at lower levels. In parallel, the ELISA showed the related cytokines were present in the inner ear at concentrations higher by 2-122 fold higher at 18 h, declining slightly from there at 24 h. Immunohistochemistry with antibodies to a number of these cytokines demonstrated they occurred in greater amounts in the inner ear tissues. These findings demonstrate considerable inflammatory gene expression and gene products in the inner ear following acute otitis media. These higher cytokine levels suggest one potential mechanism for the permanent hearing loss seen in some cases of acute and chronic otitis media. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

PubMed Central

Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau

2015-01-01

Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6 -/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6 -/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6 -/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6 -/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis. PMID:26691857

Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

PubMed

Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; da Silva, Josiane Mello; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira; Scio, Elita

2014-01-01

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β -carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

Immune and Inflammatory Role in Renal Disease

PubMed Central

Ryan, Michael J.

2013-01-01

Chronic and acute renal diseases, irrespective of the initiating cause, have inflammation and immune system activation as a common underlying mechanism. The purpose of this review is to provide a broad overview of immune cells and inflammatory proteins that contribute to the pathogenesis of renal disease, and to discuss some of the physiological changes that occur in the kidney as a result of immune system activation. An overview of common forms of acute and chronic renal disease is provided, followed by a discussion of common therapies that have antiinflammatory or immunosuppressive effects in the treatment of renal disease. PMID:23720336

Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination

PubMed Central

Guglielmetti, C.; Veraart, J.; Roelant, E.; Mai, Z.; Daans, J.; Van Audekerke, J.; Naeyaert, M.; Vanhoutte, G.; Delgado y Palacios, R.; Praet, J.; Fieremans, E.; Ponsaerts, P.; Sijbers, J.; Van der Linden, A.; Verhoye, M.

2016-01-01

Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, MK, RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stage of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event. PMID:26525654

THE ACUTE PHASE RESPONSE INDUCED BY BRONCHOSCOPY WITH LAVAGE

EPA Science Inventory

Bronchoscopy has been used to evaluate the inflammatory responses in vitro and in vivo. The procedure may affect acute inflammation in the lower respiratory tract. We reviewed consecutive bronchoscopies done in normal healthy non-smokers between April, 1998 and April, 2004. The...

Identification of relevant functional issues for the care of patients with acute arthritis by health professionals, using the ICF framework and a multi-disciplinary focus group approach.

PubMed

Zochling, J; Grill, E; Alten, R; Ernst, J; Stucki, G; Braun, J

2007-01-01

To identify the most relevant problems to be addressed in the multi-disciplinary care of patients with acute arthritis using focus groups of health professionals followed by a Delphi process. Focus group and Delphi methodology were applied. The focus groups were conducted at three specialist rheumatology hospital clinics in Germany, each group comprising rheumatologists, nurses, physiotherapists, occupational therapists, psychologists and social workers. The participants were asked to decide which categories of the International Classification of Functioning, Disability and Health (ICF) are relevant to the care of patients with acute inflammatory arthritis. The results from the focus groups were then followed by an anonymous Delphi process. Twenty-six health professionals participated in the 3 focus groups. 167 of the second-level ICF categories (63% of all second-level categories) were considered as relevant by the rheumatology health professionals. Items from all four components, Body Functions, Body Structures, Activities and Participation and Environmental Factors were represented. Agreement between focus groups and between different health professional groups was substantial for all components with the exception of Environmental Factors (Cohen's kappa 0.23). The involvement of experts from different health professions is a valuable tool to identify typical patient characteristics, expressed as distinct ICF categories, to aid in patient care in the acute rheumatology setting. Acute patient care cannot and should not be separated from ongoing long-term management.

Genetic Response of Rat Supraspinatus Tendon and Muscle to Exercise

PubMed Central

Rooney, Sarah Ilkhanipour; Tobias, John W.; Bhatt, Pankti R.; Kuntz, Andrew F.; Soslowsky, Louis J.

2015-01-01

Inflammation is a complex, biologic event that aims to protect and repair tissue. Previous studies suggest that inflammation is critical to induce a healing response following acute injury; however, whether similar inflammatory responses occur as a result of beneficial, non-injurious loading is unknown. The objective of this study was to screen for alterations in a subset of inflammatory and extracellular matrix genes to identify the responses of rat supraspinatus tendon and muscle to a known, non-injurious loading condition. We sought to define how a subset of genes representative of specific inflammation and matrix turnover pathways is altered in supraspinatus tendon and muscle 1) acutely following a single loading bout and 2) chronically following repeated loading bouts. In this study, Sprague-Dawley rats in the acute group ran a single bout of non-injurious exercise on a flat treadmill (10 m/min, 1 hour) and were sacrificed 12 or 24 hours after. Rats in the chronic group ran 5 days/wk for 1 or 8 weeks. A control group maintained normal cage activity. Supraspinatus muscle and tendon were harvested for RNA extractions, and a custom Panomics QuantiGene 2.0 multiplex assay was used to detect 48 target and 3 housekeeping genes. Muscle/tendon and acute/chronic groups had distinct gene expression. Components of the arachidonic acid cascade and matrix metalloproteinases and their inhibitors were altered with acute and chronic exercise. Collagen expression increased. Using a previously validated model of non-injurious exercise, we have shown that supraspinatus tendon and muscle respond to acute and chronic exercise by regulating inflammatory- and matrix turnover-related genes, suggesting that these pathways are involved in the beneficial adaptations to exercise. PMID:26447778

Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist.

PubMed

Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T

2014-07-01

Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1), in acute/chronic pancreatitis; however, the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues and the effects of CX3CL1 on activated PSCs. CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues was evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated PSCs were examined with real-time polymerase chain reaction, BrdU (5-bromo-2-deoxyuridine) assays, and Western blotting. In normal pancreas, acinar cells expressed CX3CR1 within granule-like formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal, and activated PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1 did not induce inflammatory genes expression in activated PSCs, but induced proliferation. CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis, and the CX3CR1s are activated. CX3CL1 induces proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSC proliferation in pancreatitis where CX3CL1 levels are elevated.

Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas, acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist

PubMed Central

Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T.

2014-01-01

Objectives Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1) in acute/chronic pancreatitis, however the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues, and the effects of CX3CL1 on activated-PSCs. Methods CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues were evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated-PSCs were examined with realtime-PCR, BrdU assays and Western Blotting. Results In normal pancreas, acinar cells expressed CX3CR1 within granule-like-formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal and activated-PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1, did not induce inflammatory-genes expression in activated-PSCs, but induced proliferation. Conclusions CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis and the CX3CR1s are activated. CX3CL1 induces proliferation of activated-PSCs without increasing release of inflammatory-mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSCs proliferation in pancreatitis where CX3CL1 levels are elevated. PMID:24681877

Acute kidney injury post-major orthopaedic surgery: A single-Centre case-control study.

PubMed

Ying, Tracey; Chan, Samantha; Lane, Stephen; Somerville, Christine

2018-02-01

To identify risk factors for acute kidney injury following major orthopaedic surgery. We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. We reviewed the patients' history of cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus along with presence of sepsis and obesity. Associations of hypothetical risk factors were estimated using conditional logistic regression. We identified 164 cases of AKI in an elderly cohort (median age = 73 years). Controlling for baseline comorbidities, both diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were found to be associated with a twofold risk of acute kidney injury (diuretic - OR 2.06 95% CI:1.30-3.26, P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use OR 2.09 95% CI:1.31-3.32, P < 0.005). A dose-effect model accounting for perioperative nonsteroidal anti-inflammatory drug administration demonstrated a linear relationship between the number of times these drugs were given and postoperative acute kidney injury risk (OR 1.35 95% CI:1.05-1.73, P = 0.02). We identified perioperative diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to be significantly associated with postoperative AKI. Further prospective studies are required to confirm this. © 2016 Asian Pacific Society of Nephrology.

Overexpression of alpha(1)-acid glycoprotein in transgenic mice leads to sensitisation to acute colitis.

PubMed

Hochepied, T; Wullaert, A; Berger, F G; Baumann, H; Brouckaert, P; Steidler, L; Libert, C

2002-09-01

alpha(1)-Acid glycoprotein (alpha(1)-AGP) is an acute phase protein in most mammalian species whose concentration rises 2-5-fold during an acute phase reaction. Its serum concentration has often been used as a marker of disease, including inflammatory bowel disease (IBD). High alpha(1)-AGP levels were found to have a prognostic value for an increased risk of relapse in IBD. To investigate a possible role for increased serum levels of alpha(1)-AGP in the development of IBD. Dextran sodium sulphate (DSS) 2% was added to the drinking water of transgenic mice, overexpressing the rat alpha(1)-AGP gene, to induce acute colitis, thus mimicking the conditions of relapse. Clinical parameters, inflammatory parameters, and histological analyses on colon sections were performed. Homozygous alpha(1)-AGP-transgenic mice started losing weight and showed rectal bleeding significantly earlier than heterozygous transgenic or wild-type mice. Survival time of homozygous transgenic mice was significantly shorter compared with heterozygous and wild-type mice. The higher susceptibility of homozygous alpha(1)-AGP-transgenic mice to DSS induced acute colitis was also reflected in higher local myeloperoxidase levels, higher inflammation scores of the colon, and higher systemic levels of interleukin 6 and serum amyloid P component. Local inflammatory parameters were also significantly different in heterozygous transgenic mice compared with wild-type mice, indicating a local dosage effect. In homozygous transgenic mice, significantly higher amounts of bacteria were found in organs but IgA levels were only slightly lower than those of control mice. Sufficiently high serum levels of alpha(1)-AGP result in a more aggressive development of acute colitis.

Luteolin Suppresses Inflammatory Mediator Expression by Blocking the Akt/NFκB Pathway in Acute Lung Injury Induced by Lipopolysaccharide in Mice.

PubMed

Li, Yi-Ching; Yeh, Chung-Hsin; Yang, Ming-Ling; Kuan, Yu-Hsiang

2012-01-01

Acute lung injury (ALI), instilled by lipopolysaccharide (LPS), is a severe illness with excessive mortality and has no specific treatment strategy. Luteolin is an anti-inflammatory flavonoid and widely distributed in the plants. Pretreatment with luteolin inhibited LPS-induced histological changes of ALI and lung tissue edema. In addition, LPS-induced inflammatory responses, including increased vascular permeability, tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), were also reduced by luteolin in a concentration-dependent manner. Furthermore, luteolin suppressed activation of NFκB and its upstream molecular factor, Akt. These results suggest that the protection mechanism of luteolin is by inhibition of NFκB activation possibly via Akt.

A Method of Treatment of Purulent-Inflammatory Diseases of the Hand in Outpatient Clinic with Using Electromagnetic Microwave Field

NASA Astrophysics Data System (ADS)

Rabenok, L.; Grimalsky, V.; De La Hidalga-W., J.

2006-09-01

The report is devoted to applications of the microwave therapy. 50 patients with acute purulent-inflammatory diseases of the hand were examined with using our method of treatment with electromagnetic (EM) microwave field in an outpatient clinic. We used a portable apparatus that operates in the millimeter (mm) wave range in 4 regimes. The intensity of EM radiation was 2-10 mW/cm2. A peculiarity of the method was an absence of any antibacterial medicine during the treatment. We conclude that using EM microwave fields seems very efficient in a complex treatment of acute purulent-inflammatory diseases of the hand in an outpatient clinic. An interpretation of the obtained results is given due to the resonant character of the interaction of EM radiation with molecular and cellular structures.

Anti-inflammatory effects of aqueous extract of Mangifera indica in Wistar rats.

PubMed

Oluwole, Oluwafemi Gabriel; Esume, Celestine

2015-05-01

Recent studies in standard laboratories have indicated that a typical mango stem bark aqueous extract (Magnifera indica Linn) possess anti-malaria and anti-fever properties. Recent information also exists in the literature, suggesting its potency as a very effective anti-inflammatory plant extract. This study will therefore contribute immensely to the systemic search for a useful, less toxic and natural bioactive medicinal compound. This study investigated the anti-inflammatory effects of the aqueous extract of Mangifera indica (MI) in a carrageenin-induced rat paw oedema model of acute inflammation. Rats (n=5) were treated orally with MI (50, 100 and 200 mg/kg), acetylsalicylic acid (100 mg/kg) or distilled water (3 mL). Thirty minutes later, acute inflammation was induced with a sub-plantar injection of 0.1 mL of 1% carrageenin solution into the right hind paw of the rats. The paw oedema sizes were measured with the aid of a Vernier calliper over a period of 3 hours. The aqueous extract of MI (50-200 mg/kg, p.o.) produced a dose-dependent and significant inhibition of the acute inflammation induced by the carrageenin in rats when compared with controls. The percentage inhibition of oedema formation produced by MI (200 mg/kg, p.o.) was similar to that elicited by acetylsalicylic acid (100 mg/kg, p.o.). The results of this preliminary investigation suggest that MI contains active compounds with an anti-inflammatory activity. However, more detailed studies using additional models are necessary to further characterise the effects of MI in inflammatory disorders.

Fluid resuscitation with lactated Ringer’s solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial

PubMed Central

Herrera-Marante, Iván; González-Camacho, Verónica; Bonjoch, Laia; Quesada-Vázquez, Noé; Almenta-Saavedra, Isabel; Miralles-Maciá, Cayetano; Acevedo-Piedra, Nelly G; Roger-Ibáñez, Manuela; Sánchez-Marin, Claudia; Osuna-Ligero, Rosa; Gracia, Ángel; Llorens, Pere; Zapater, Pedro; Singh, Vikesh K; Moreu-Martín, Rocío; Closa, Daniel

2017-01-01

Background Little is known regarding the optimal type of fluid resuscitation in acute pancreatitis (AP). Objective The objective of this article was to compare the effect of lactated Ringer’s solution (LR) vs normal saline (NS) in the inflammatory response in AP. Methods We conducted a triple-blind, randomized, controlled trial. Patients ≥ 18 admitted with AP were eligible. Patients were randomized to receive LR or NS. Primary outcome variables were number of systemic inflammatory response syndrome (SIRS) criteria at 24 hours, 48 hours and 72 hours and blood C-reactive protein (CRP) levels at 48 hours and 72 hours. In vitro complementary experiments were performed to further explore the interaction between pH, lactate and inflammation. Results Nineteen patients receiving LR and 21 receiving NS were analyzed. The median (p25–p75) number of SIRS criteria at 48 hours were 1 (1–2) for NS vs 1 (0–1) for LR, p = 0.060. CRP levels (mg/l) were as follows: at 48 hours NS 166 (78–281) vs LR 28 (3–124), p = 0.037; at 72 hours NS 217 (59–323) vs LR 25 (3–169), p = 0.043. In vitro, LR inhibited the induction of inflammatory phenotype of macrophages and NF-κB activation. This effect was not observed when using Ringer’s solution without lactate, suggesting a direct anti-inflammatory effect of lactate. Conclusions Lactated Ringer’s is associated with an anti-inflammatory effect in patients with acute pancreatitis. PMID:29435315

Targeting myeloid differentiation protein 2 by the new chalcone L2H21 protects LPS-induced acute lung injury.

PubMed

Zhang, Yali; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Pan, Zheer; Huang, Yi; Mei, Liqin; Dai, Yuanrong; Liu, Xing; Shan, Xiaoou; Liang, Guang

2017-04-01

Acute inflammatory diseases are the leading causes of mortality in intensive care units. Myeloid differentiation 2 (MD-2) is required for recognizing lipopolysaccharide (LPS) by toll-like receptor 4 (TLR4), and represents an attractive therapeutic target for LPS-induced inflammatory diseases. In this study, we report a chalcone derivative, L2H21, as a new MD2 inhibitor, which could inhibit LPS-induced inflammation both in vitro and in vivo. We identify that L2H21 as a direct inhibitor of MD-2 by binding to Arg 90 and Tyr 102 residues in MD-2 hydrophobic pocket using a series of biochemical experiments, including surface plasmon response, molecular docking and amino acid mutation. L2H21 dose dependently inhibited LPS-induced inflammatory cytokine expression in primary macrophages. In mice with LPS intratracheal instillation, L2H21 significantly decreased LPS-induced pulmonary oedema, pathological changes in lung tissue, protein concentration increase in bronchoalveolar lavage fluid, inflammatory cells infiltration and inflammatory gene expression, accompanied with the decrease in pulmonary TLR4/MD-2 complex. Meanwhile, administration with L2H21 protects mice from LPS-induced mortality at a degree of 100%. Taken together, this study identifies a new MD2 inhibitor L2H21 as a promising candidate for the treatment of acute lung injury (ALI) and sepsis, and validates that inhibition of MD-2 is a potential therapeutic strategy for ALI. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study

PubMed Central

Milaneschi, Yuri; Zhang, Yongqing; Becker, Kevin G.; Zukley, Linda; Ferrucci, Luigi

2017-01-01

Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (P<0.001). No significant differences were observed after lowering of uric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies. Trial Registration: ClinicalTrials.gov NCT01323335 PMID:28786993

Taraxerol, a pentacyclic triterpene from Abroma augusta leaf, attenuates acute inflammation via inhibition of NF-κB signaling.

PubMed

Khanra, Ritu; Dewanjee, Saikat; Dua, Tarun K; Bhattacharjee, Niloy

2017-04-01

Abroma augusta L. (Malvaceae) leaf is traditionally used to treat inflammatory disorders. In our laboratory, we have scientifically validated the anti-inflammatory effect of A. augusta leaf extract. In this study, it has been aimed to evaluate in vivo anti-inflammatory effect of taraxerol isolated from the methanol extract of A. augusta leaf. It was further intended to find out the probable mechanism of anti-inflammatory effect of taraxerol. The anti-inflammatory effect of taraxerol (5 and 10mg/kg, i.p.) was measured employing carrageenan-induced paw edema model of acute inflammation. The carrageenan injection resulted significant edema formation in the right paw when compared with un-injected left paw. However, taraxerol (10mg/kg) treatment could significantly (p<0.05-0.01) attenuate carrageenan induced paw edema 2h onward. The effect of taraxerol at the dose of 5mg/kg was found to be significant (p<0.05) only after 4h of carrageenan treatment. Taraxerol (10mg/kg) treatment could significantly (p<0.01) attenuate carrageenan mediated up-regulation in the levels of IL 1β, IL 6, IL 12 and TNF α in the right paw tissues. In search of molecular mechanism, taraxerol (10mg/kg) could significantly (p<0.05-0.01) reinstate carrageenan provoked NF-κB signaling and thereby caused significant down-regulation in the expressions of COX-2 (p<0.01) and iNOS (p<0.05). In conclusion, taraxerol would attenuate acute inflammation via inhibition of NF-κB signaling. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation.

PubMed

Johnson, Ariel M; Kurti, Stephanie P; Smith, Joshua R; Rosenkranz, Sara K; Harms, Craig A

2016-03-01

A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 ± 3.2 years; height, 178.9 ± 5.5 cm; weight, 78.5 ± 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENO increased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENO and TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men.

In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

PubMed Central

Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

2017-01-01

Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of tissue damage free of MR contrast agents. PMID:28264039

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids

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

Jonasson, Sofia, E-mail: sofia.jonasson@foi.se; Wigenstam, Elisabeth; Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå

Chlorine (Cl{sub 2}) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl{sub 2}-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200 ppm Cl{sub 2} during 15 min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24 h or 14 days post-exposure. A single dose of themore » corticosteroid dexamethasone (10 or 100 mg/kg) was administered intraperitoneally 1, 3, 6, or 12 h following Cl{sub 2} exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6 h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1 h was dose-dependent; high-dose significantly reduced acute airway inflammation (100 mg/kg) but not treatment with the relatively low-dose (10 mg/kg). Both doses reduced AHR 14 days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl{sub 2} exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl{sub 2} exposure. - Highlights: • Inhalation of Cl{sub 2} may lead to a long-standing airway hyperresponsiveness. • The symptoms in Cl{sub 2}-exposed mice are similar to those described for RADS in humans. • Corticosteroids prevent delayed symptoms such as AHR in Cl{sub 2}-induced lung injury. • Early medical intervention of corticosteroids is of importance. • Treatment with corticosteroids alone is insufficient to counteract acute lung injury.« less

Effect of hydrogen sulfide on inflammatory cytokines in acute myocardial ischemia injury in rats

PubMed Central

LIU, FANG; LIU, GUANG-JIE; LIU, NA; ZHANG, GANG; ZHANG, JIAN-XIN; LI, LAN-FANG

2015-01-01

Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. PMID:25667680

Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

PubMed Central

Elena, Talero; Rosanna, Di Paola; Emanuela, Mazzon; Esposito, Emanuela; Virginia, Motilva; Salvatore, Cuzzocrea

2012-01-01

Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors. PMID:22685374

Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

PubMed Central

Kaspar, Felix; Jelinek, Herbert F.; Perkins, Steven; Al-Aubaidy, Hayder A.; deJong, Bev; Butkowski, Eugene

2016-01-01

Objective. This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p = 0.047) and a decrease of MCP-1 (−17.9%; p = 0.03). Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis. PMID:27212809

Trait Hostility and Acute Inflammatory Responses to Stress in the Laboratory

PubMed Central

Girard, Dominique; Tardif, Jean-Claude; Boisclair Demarble, Julie; D’Antono, Bianca

2016-01-01

Hostility has been associated with higher basal levels of inflammation. The present study evaluated the association of hostility with acute stress-induced changes in inflammatory activity. One hundred and ninety-nine healthy men and women, aged 19–64 years, were exposed to a stress protocol involving four interpersonal stressors. Participants completed the Cook-Medley Hostility questionnaire and provided two blood samples for the measurement of inflammatory biomarkers (CRP, Il-6, MPO, TNF-α, MCP-1, Il-8, Il-10, and Il-18), prior to and following exposure to a standardized stress protocol. In univariate analyses, hostility was associated with significantly higher TNF-α, but lower Il-8 and Il-18 values post-stress, though only Il-8 remained significant after controlling for baseline differences. In multivariate analyses, a significant Age by Hostility interaction emerged for Il-6, while sex moderated the relation between hostility and Il-10 reactivity. Following stress, hostility was associated with greater pro-inflammatory Il-6 activity among younger individuals and to decreased anti-inflammatory Il-10 activity in women. Future research is needed to replicate these findings and to evaluate their implication for disease. PMID:27270459

Treatment of inflammatory diseases with mesenchymal stem cells.

PubMed

Newman, Robert E; Yoo, Dana; LeRoux, Michelle A; Danilkovitch-Miagkova, Alla

2009-06-01

Human mesenchymal stem cells (hMSCs) are rare progenitor cells present in adult bone marrow that have the capacity to differentiate into a variety of tissue types, including bone, cartilage, tendon, fat, and muscle. In addition to multilineage differentiation capacity, MSCs regulate immune and inflammatory responses, providing therapeutic potential for treating diseases characterized by the presence of an inflammatory component. The availability of bone marrow and the ability to isolate and expand hMSCs ex vivo make these cells an attractive candidate for drug development. The low immunogenicity of these cells suggests that hMSCs can be transplanted universally without matching between donors and recipients. MSCs universality, along with the ability to manufacture and store these cells long-term, present a unique opportunity to produce an "off-the-shelf" cellular drug ready for treatment of diseases in acute settings. Accumulated animal and human data support MSC therapeutic potential for inflammatory diseases. Several phase III clinical trials for treatment of acute Graft Versus Host Disease (GVHD) and Crohn's disease are currently in progress. The current understanding of cellular and molecular targets underlying the mechanisms of MSCs action in inflammatory settings as well as clinical experience with hMSCs is summarized in this review.

An Endocannabinoid Uptake Inhibitor from Black Pepper Exerts Pronounced Anti-Inflammatory Effects in Mice.

PubMed

Reynoso-Moreno, Inés; Najar-Guerrero, Israel; Escareño, Noé; Flores-Soto, Mario Eduardo; Gertsch, Jürg; Viveros-Paredes, Juan Manuel

2017-11-01

Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and Piper longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1% inhibition of inflammatory pain at 2.5 mg/kg ip and 50.0 ± 15.9% inhibition of edema formation at 5 mg/kg ip) and acute analgesia (66.1 ± 28.1% inhibition at 5.0 mg/kg ip) were observed. Moreover, guineensine inhibited proinflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy, but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant, but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels, and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A, and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.

ACUTE OZONE-INDUCED INFLAMMATORY GENE EXPRESSION IN THE RAT LUNG IS NOT RELATED TO LEVELS OF ANTIOXIDANTS IN THE LAVAGE FLUID

EPA Science Inventory

ABSTRACT BODY: Ozone causes oxidative stress and lung inflammation. We hypothesized that rat strains with or without genetic susceptibility to cardiovascular disease will have different antioxidant levels in alveolar lining, and that ozone induced inflammatory gene expression wil...

DIESEL EXHAUST PARTICULATE (DEP)-INDUCED ACTIV ATION OF STAT3 REQUIRES ACTIVITIES OF EGFR AND SRC IN AIRWAY EPITHELIAL CELLS

EPA Science Inventory

In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory responses in the lung characterized by inflammatory cell influx and elevated expression of mediators such as cytokines, and chemokines. Signal transducers and activators of transcription (STAT) protein...

Inflammatory process induced by carrageenan in adjacent tissue triggers the acute inflammation in deep digital flexor tendon of rats.

PubMed

Vieira, Cristiano Pedrozo; De Aro, Andrea Aparecida; Da Ré Guerra, Flávia; De Oliveira, Letícia Prado; De Almeida, Marcos Dos Santos; Pimentel, Edson Rosa

2013-08-01

Tendinopathy is a pathology found mainly in the rotator cuff, patellar, Achilles and flexor tendons. Tendinopathy is a significant impediment to performance in athletes and in workers in the labor market. Some studies have indicated that inflammation in adjacent tissues may affect the rotator cuff and Achilles tendon. In this study alterations were verified in the extracellular matrix (ECM) of the deep digital flexor tendon after two periods (12 and 24 hr) of induction inflammation in rat paw. Wistar rats were divided into three groups: those that received injection of 1% carrageenan; those that received 0.9% NaCl; and those that received no application. The tendon was divided into distal (d), proximal (p), and intermediate (i) regions. Biochemical analyses were performed and included non-collagenous proteins (NCP), glycosaminoglycans (GAGs), hydroxyproline (HoPro) and metalloproteinases 2 and 9. Tissue sections were stained with toluidine blue, hematoxylin-eosin, and Ponceau SS and observed under polarization microscopy. Remarkable results were detected that included the presence of MMP-9, degradation of NCP and GAG and the presence of cellular infiltrate closer to digits in d region. The different concentrations of HoPro, as well as alterations in the organization of the collagen fibers showed the collagenous matrix undergoing some alterations. The results indicated that the induced inflammation in rat paw exhibited characteristics similar to the typical acute inflammatory process observed in tendons. Copyright © 2013 Wiley Periodicals, Inc.

The effect of cardioprotective diet rich with natural antioxidants on chronic inflammation and oxidized LDL during cardiac rehabilitation in patients after acute myocardial infarction.

PubMed

Mlakar, Polona; Salobir, Barbara; Čobo, Nusret; Strašek, Janja; Prezelj, Marija; Debevc, Ana; Jug, Borut; Terčelj, Marjeta; Šabovič, Mišo

2015-06-01

Chronic inflammation, the fundamental pathogenetic process of atherosclerosis, can be modified by pharmacological and non-pharmacological measures as a part of secondary prevention after acute myocardial infarction (AMI). The aim of our study was to determine the effect of diet, rich with natural antioxidants, added to physical activity (as a part of cardiac rehabilitation (CR) program) on inflammatory markers and ox-LDL, a marker of oxidative stress, closely involved in the process of chronic inflammation. 41 male patients after AMI undergoing CR were divided into a diet group (supervised cardioprotective diet throughout the CR), and control group (CR without diet). We measured hsCRP, leucocytes, neutrophils, IL-6, oxLDL, exercise capacity and classic risk factors before and after CR program. Patients from the diet group presented with a significant decline in classic risk factors (BMI, waist circumference, waist to hip ratio, systolic blood pressure, heart rate, blood glucose, total cholesterol, LDL, TAG) and inflammatory markers (hsCRP, leucocytes, neutrophils) compared to control group. Furthermore, when studying nonsmokers, we observed significant decline of oxLDL in the diet group. The addition of cardioprotective diet, rich with natural antioxidants, to physical activity as a part of a CR program, positively modifies not just classic risk factors and exercise capacity, but also diminishes chronic inflammation markers. These effects, and oxLDL decline were most prominent in nonsmoking patients.

MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals

PubMed Central

Chen, Chun-Jen; Shi, Yan; Hearn, Arron; Fitzgerald, Kate; Golenbock, Douglas; Reed, George; Akira, Shizuo; Rock, Kenneth L.

2006-01-01

While it is known that monosodium urate (MSU) crystals cause the disease gout, the mechanism by which these crystals stimulate this inflammatory condition has not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction adaptor myeloid differentiation primary response protein 88 (MyD88) is required for acute gouty inflammation. In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells expressing TLR1–11 to activate NF-κB. In contrast, mice deficient in the MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1 production and IL-1R activation play essential roles in MSU-triggered inflammation. IL-1R deficiency in bone marrow–derived cells did not affect the inflammatory response; however, it was required in non–bone marrow–derived cells. These results indicate that IL-1 is essential for the MSU-induced inflammatory response and that the requirement of MyD88 in this process is primarily through its function as an adaptor molecule in the IL-1R signaling pathway. PMID:16886064

Dual-seq transcriptomics reveals the battle for iron during Pseudomonas aeruginosa acute murine pneumonia

PubMed Central

Damron, F. Heath; Oglesby-Sherrouse, Amanda G.; Wilks, Angela; Barbier, Mariette

2016-01-01

Determining bacterial gene expression during infection is fundamental to understand pathogenesis. In this study, we used dual RNA-seq to simultaneously measure P. aeruginosa and the murine host’s gene expression and response to respiratory infection. Bacterial genes encoding products involved in metabolism and virulence were differentially expressed during infection and the type III and VI secretion systems were highly expressed in vivo. Strikingly, heme acquisition, ferric-enterobactin transport, and pyoverdine biosynthesis genes were found to be significantly up-regulated during infection. In the mouse, we profiled the acute immune response to P. aeruginosa and identified the pro-inflammatory cytokines involved in acute response to the bacterium in the lung. Additionally, we also identified numerous host iron sequestration systems upregulated during infection. Overall, this work sheds light on how P. aeruginosa triggers a pro-inflammatory response and competes for iron with the host during infection, as iron is one of the central elements for which both pathogen and host fight during acute pneumonia. PMID:27982111

Taraxacum officinale protects against cholecystokinin-induced acute pancreatitis in rats

PubMed Central

Seo, Sang-Wan; Koo, Hyun-Na; An, Hyo-Jin; Kwon, Kang-Beom; Lim, Byung-Cheal; Seo, Eun-A; Ryu, Do-Gon; Moon, Goo; Kim, Hong-Yeoul; Kim, Hyung-Min; Hong, Seung-Heon

2005-01-01

AIM: Taraxacum officinale (TO) has been frequently used as a remedy for inflammatory diseases. The aim of this study was to investigate the effect of TO on cholecystokinin (CCK)-octapeptide-induced acute pancreatitis in rats. METHODS: TO at 10 mg/kg was orally administered, followed by 75 μg/kg CCK octapeptide injected subcutaneously three times after 1, 3 and 5 h. This whole procedure was repeated for 5 d. We determined the pancreatic weight/body weight ratio, the levels of pancreatic HSP60 and HSP72, and the secretion of pro-inflammatory cytokines. Repeated CCK octapeptide treatment resulted in typical laboratory and morphological changes of experimentally-induced pancreatitis. RESULTS: TO significantly decreased the pancreatic weight/body weight ratio in CCK octapeptide-induced acute pancreatitis. TO also increased the pancreatic levels of HSP60 and HSP72. Additionally, the secretion of IL-6 and TNF-α decreased in the animals treated with TO. CONCLUSION: TO may have a protective effect against CCK octapeptide-induced acute pancreatitis. PMID:15641154

[Effects of caspase-1 inhibitor VX765 on cold-restraint stress-induced acute gastric ulcer in mice].

PubMed

Zheng, S Q; Hong, X D; Chen, T S; Luo, P F; Xiao, S C

2017-11-20

Objective: To investigate the protective effects of caspase-1 inhibitor VX765 on gastric mucosa of mice with cold-restraint stress-induced acute gastric ulcer. Methods: Twenty-four specific pathogen free male C57BL/6J mice were divided into normal control group (NC), cold restrain group (CR), VX765 pre-treatment+ cold restrain group (VCR), and rabeprazole pre-treatment+ cold restrain group (RCR) according to the random number table, with 6 mice in each group. Mice in group NC were injected intraperitoneally with solution of 10 mL/kg dimethylsulfoxide (DMSO) and phosphate buffer solution (PBS). Mice in group CR were inflicted with acute gastric ulcer induced by cold-restraint stress 30 minutes after intraperitoneal injection of solution of DMSO and PBS. Mice in groups VCR and RCR were inflicted with acute gastric ulcer as above 30 minutes after intraperitoneal injection of solution of DMSO and PBS with dose of 12.5 μmol/kg containing 10 mg VX765 and 40 mg/kg containing 20 mg rabeprazole, respectively. Four hour after cold-restraint stress, serum content of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)was determined by enzyme-linked immunosorbent assay. Gross condition of gastric tissue was observed. Ulcer index was evaluated. Pathological change of gastric tissue was observed with HE staining. The relative expression of IL-1β, IL-18, and cleaved-caspase-1 in gastric tissue were detected by Western blotting. Mice in group NC were detected as above at the same time point. Data were processed with one-way analysis of variance and Bonferroni test. Results: The serum content of TNF-α and IL-6 and the relative expression of cleaved-caspase-1, IL-1β, and IL-18 in gastric tissue of mice in group NC were significantly lower than those in group CR (with P values below 0.01). The content of the above-mentioned inflammatory indexes in serum and gastric tissue of mice in group VCR was significantly lower than that in group CR (with P values below 0.01). There were no statistically significant differences in content of the above-mentioned inflammatory indexes in serum and gastric tissue of mice between groups RCR and CR (with P values above 0.05). The content of the above-mentioned inflammatory indexes in serum and gastric tissue of mice in group VCR was significantly lower than that in group RCR (with P values below 0.01). Surface of gastric mucosa was smooth and morphology of mucosal cells was normal with clear structure of mice in group NC. Multiple hemorrhage of gastric mucosa, disorderly arrangement of mucosal cells, and large number of inflammatory cell infiltration around necrotic tissue were observed in mice of group CR. Decreased number of gastric mucosa bleeding, intact mucosal structure, and small amount of inflammatory cell infiltration around necrotic tissue were observed in mice of groups VCR and RCR. The ulcer indexes of mice in groups NC, CR, VCR, and RCR were 0, 18.7±1.1, 6.3±1.5, and 8.2±1.3, respectively. The ulcer index of mice in group NC was significantly lower than that in the other 3 groups (with P values below 0.05). The ulcer indexes of mice in groups VCR and RCR were close ( P >0.05), which were significantly lower than ulcer index of mice in group CR (with P values below 0.05). Conclusions: VX765 can effectively inhibit the activation of caspase-1, reduce production of inflammatory factor, and alleviate inflammatory response, which have protective effects on gastric mucosa of mice with cold-restraint stress-induced acute gastric ulcer.

Effects of resistance training on the inflammatory response

PubMed Central

Calle, Mariana C

2010-01-01

Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases. PMID:20827340

Differences between Acute-onset Chronic Inflammatory Demyelinating Polyneuropathy (A-CIDP) and Acute Inflammatory Demyelinating Polyneuropathy (AIDP) in adult patients.

PubMed

Alessandro, Lucas; Pastor Rueda, José M; Wilken, Miguel; Querol Gutiérrez, Luis A; Marrodán, Mariano; Acosta, Julián N; Rivero, Alberto; Barroso, Fabio; Farez, Mauricio F

2018-03-30

Acute Inflammatory Demyelinating Polyneuropathy (AIDP) and Acute-onset Chronic Inflammatory Demyelinating Polyneuropathy (A-CIDP) are conditions presenting overlapping clinical features during early stages (first 4 weeks), although the latter may progress after 8 weeks. The aim of this study was to identify predictive factors contributing to their differential diagnosis. Clinical records of adult patients with AIDP or A-CIDP diagnosed at our institution between January-2006 and July-2017 were retrospectively reviewed. Demographic characteristics, clinical manifestations, cerebrospinal-fluid (CSF) findings, treatment and clinical evolution were analyzed. Nerve conduction studies were performed in all patients with at least 12 months follow-up. A total of 91 patients were included (AIDP, n=77; A-CIDP, n=14). The median age was 55.5 years in patients with A-CIDP vs. 43 years in AIDP (p=0.07). The history of diabetes mellitus was more frequent in A-CIDP (29% vs. 8%, p=0.04). No significant differences between groups were observed with respect to: HIV status, presence of autoimmune disorder or oncologic disease. Cranial, motor and autonomic nerve involvement rates were similar in both groups. Patients in the A-CIDP group showed higher frequency of proprioceptive disturbances (83% vs. 28%; p<0.001), sensory ataxia (46% vs. 16%; p=0.01) and the use of combined immunotherapy with corticoids (29% vs. 3%; p=0.005). There were no significant differences in CSF findings, ICU admission or mortality rates. During the first 8 weeks both entities are practically indistinguishable. Alterations in proprioception could suggest A-CIDP. Searching for markers that allow early differentiation could favor the onset of corticotherapy without delay. This article is protected by copyright. All rights reserved.

Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage.

PubMed

Naveca, Felipe Gomes; Pontes, Gemilson Soares; Chang, Aileen Yu-Hen; Silva, George Allan Villarouco da; Nascimento, Valdinete Alves do; Monteiro, Dana Cristina da Silva; Silva, Marineide Souza da; Abdalla, Lígia Fernandes; Santos, João Hugo Abdalla; Almeida, Tatiana Amaral Pires de; Mejía, Matilde Del Carmen Contreras; Mesquita, Tirza Gabrielle Ramos de; Encarnação, Helia Valeria de Souza; Gomes, Matheus de Souza; Amaral, Laurence Rodrigues; Campi-Azevedo, Ana Carolina; Coelho-Dos-Reis, Jordana Graziela; Antonelli, Lis Ribeiro do Vale; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Ramasawmy, Rajendranath

2018-05-14

Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. To define the immunologic biomarkers that correlate with acute ZIKV infection. We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.

Endotoxin-induced lung alveolar cell injury causes brain cell damage.

PubMed

Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia R M; Pelosi, Paolo; Villar, Jesús

2015-01-01

Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. © 2014 by the Society for Experimental Biology and Medicine.

Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage

PubMed Central

Naveca, Felipe Gomes; Pontes, Gemilson Soares; Chang, Aileen Yu-hen; da Silva, George Allan Villarouco; do Nascimento, Valdinete Alves; Monteiro, Dana Cristina da Silva; da Silva, Marineide Souza; Abdalla, Lígia Fernandes; Santos, João Hugo Abdalla; de Almeida, Tatiana Amaral Pires; Mejía, Matilde del Carmen Contreras; de Mesquita, Tirza Gabrielle Ramos; Encarnação, Helia Valeria de Souza; Gomes, Matheus de Souza; Amaral, Laurence Rodrigues; Campi-Azevedo, Ana Carolina; Coelho-dos-Reis, Jordana Graziela; Antonelli, Lis Ribeiro do Vale; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Ramasawmy, Rajendranath

2018-01-01

BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application. PMID:29768624

Acute Respiratory Infection and Use of Nonsteroidal Anti-Inflammatory Drugs on Risk of Acute Myocardial Infarction: A Nationwide Case-Crossover Study.

PubMed

Wen, Yao-Chun; Hsiao, Fei-Yuan; Chan, K Arnold; Lin, Zhen-Fang; Shen, Li-Jiuan; Fang, Cheng-Chung

2017-02-15

Previous studies have suggested that acute respiratory infection (ARI) and nonsteroidal anti-inflammatory drugs (NSAIDs) use could trigger acute myocardial infarction (AMI). In some countries, physicians prescribe NSAIDs for patients with ARI for symptom relief. However, there is no research evaluating whether NSAIDs use during ARI episodes may increase the risk of AMI. We identified 9793 patients with an incident hospitalization of AMI (index date) between 2007 and 2011. Using case-crossover design, we compared the following exposure status between the case (1-7-day before index date) and matched control period (366-372-day before index date): NSAIDs use during ARI episodes, ARI episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable conditional logistic regression models were used to estimate odds ratios adjusted for potential confounders. Nonsteroidal anti-inflammatory drugs use during ARI was associated with a 3.4-fold increased risk of AMI (adjusted odds ratio [aOR] = 3.41; 95% confidence interval [CI] = 2.80-4.16), ARI without NSAIDs use was associated with a 2.7-fold increased risk (aOR = 2.65; 95% CI = 2.29-3.06), and NSAIDs use only was associated with a 1.5-fold increased risk (aOR = 1.47; 95% CI = 1.33-1.62). Moreover, parenteral NSAIDs were associated with much higher risk in ARI patients (aOR = 7.22; 95% CI = 4.07-12.81). Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially parenteral NSAIDs, was associated with a further increased risk of AMI. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

PubMed

Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

2015-08-01

Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

PubMed Central

Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B.; Jordt, Sven-Eric

2013-01-01

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis.

PubMed

Kawakubo, Kazumichi; Ohnishi, Shunsuke; Fujita, Hirotoshi; Kuwatani, Masaki; Onishi, Reizo; Masamune, Atsushi; Takeda, Hiroshi; Sakamoto, Naoya

2016-01-01

Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine and can be isolated from fetal membranes (FMs), particularly amniotic membranes. We investigated the effect of rat FM-derived MSCs (rFM-MSCs) and human amnion-derived MSCs (hAMSCs) on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis. Effect of rFM-MSCs or hAMSC-conditioned medium was investigated in vitro. Acute pancreatitis was induced by intraductal injection of 4% taurocholate, and rFM-MSCs were transplanted intravenously. Chronic pancreatitis was induced by intravenous injection of 5 mg/kg dibutyltin dichloride, and hAMSCs were transplanted intravenously. The inflammatory reaction of macrophages induced by lipopolysaccharide and trypsin was significantly suppressed by rFM-MSC coculture. Pancreatic acinar cell injury induced by cerulein was significantly ameliorated by hAMSC-conditioned medium. Pancreatic stellate cell activation induced by tumor necrosis factor-α was significantly decreased by hAMSC-conditioned medium. Transplantation of rFM-MSCs significantly reduced the histological score and infiltration of CD68-positive macrophages in the rat pancreas. The hAMSC transplantation significantly decreased the expression of MCP-1 and attenuated the downregulation of amylase expression in the pancreas. Transplantation of FM-MSCs and AMSCs suppressed the inflammatory reaction of acute and chronic pancreatitis in rats.

Definition and quantification of acute inflammatory white matter injury in the immature brain by MRI/MRS at high magnetic field.

PubMed

Lodygensky, Gregory A; Kunz, Nicolas; Perroud, Elodie; Somm, Emmanuel; Mlynarik, Vladimir; Hüppi, Petra S; Gruetter, Rolf; Sizonenko, Stéphane V

2014-03-01

Lipopolysaccharide (LPS) injection in the corpus callosum (CC) of rat pups results in diffuse white matter injury similar to the main neuropathology of preterm infants. The aim of this study was to characterize the structural and metabolic markers of acute inflammatory injury by high-field magnetic resonance imaging (MRI) magnetic resonance spectroscopy (MRS) in vivo. Twenty-four hours after a 1-mg/kg injection of LPS in postnatal day 3 rat pups, diffusion tensor imaging and proton nuclear magnetic spectroscopy ((1)H NMR) were analyzed in conjunction to determine markers of cell death and inflammation using immunohistochemistry and gene expression. MRI and MRS in the CC revealed an increase in lactate and free lipids and a decrease of the apparent diffusion coefficient. Detailed evaluation of the CC showed a marked apoptotic response assessed by fractin expression. Interestingly, the degree of reduction in the apparent diffusion coefficient correlated strongly with the natural logarithm of fractin expression, in the same region of interest. LPS injection further resulted in increased activated microglia clustered in the cingulum, widespread astrogliosis, and increased expression of genes for interleukin (IL)-1, IL-6, and tumor necrosis factor. This model was able to reproduce the typical MRI hallmarks of acute diffuse white matter injury seen in preterm infants and allowed the evaluation of in vivo biomarkers of acute neuropathology after inflammatory challenge.

Protective effect of Clerodendrum colebrookianum Walp., on acute and chronic inflammation in rats

PubMed Central

Deb, Lokesh; Dey, Amitabha; Sakthivel, G.; Bhattamishra, Subrat Kumar; Dutta, Amitsankar

2013-01-01

Aim: To evaluate antioxidant, anti-inflammatory potential of the aqueous extracts and its aqueous, n-butanol, ethyl-acetate, and chloroform fractions of Clerodendrum colebrookianum Walp. leaves. Materials and Methods: In this present study, all the test samples were evaluated on in-vivo inflammatory model such as carrageenan and histamine-induced acute-inflammation and cotton pellet induced granuloma formation in albino male rats. Test samples were also employed in in-vitro assays like DPPH* free radical scavenging activity and COX inhibition assay. Results: The test samples at the dose of 200mg/kg/p.o. were found to cause significant inhibition of carrageenan and histamine-induced inflammation and cotton pallet-induced granuloma formation on acute and chronic inflammation in rats. The test samples, except n-butanol fraction, exhibited inhibitory effect for both COX-1 and COX-2, in in-vitro assay but their percentage of inhibition values differs from each other. The test samples (aqueous extracts, aqueous, n-butanol, ethyl-acetate, and chloroform fractions) at 100 μg concentration exhibits 54.37%, 33.88%, 62.85%, 56.28%, and 57.48% DPPH* radical-scavenging effect respectively in in-vitro antioxidant study. Conclusion: These observations established the anti-inflammatory effect of C. colebrookianum leaves in acute and chronic stages of inflammation by free radical scavenging and inhibition of COX-1 and COX-2. PMID:24014914

Inflammatory parameters in Caco-2 cells: effect of stimuli nature, concentration, combination and cell differentiation.

PubMed

Van De Walle, Jacqueline; Hendrickx, Aurélie; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

2010-08-01

Enterocytes regulate gut maintenance and defence by secreting and responding to inflammatory mediators and by modulating the intestinal epithelial permeability. In order to develop an in vitro model of the acute phase of intestinal inflammation, Caco-2 cells were exposed to the inflammatory mediators IL-1beta, TNF-alpha, IFN-gamma and LPS, and the importance of several experimental parameters, i.e. cell differentiation, stimulus nature, concentration and combination on the inflammatory response was assessed by measuring the production of IL-6, IL-8, PGE-2 and NO and by evaluating the monolayer permeability. A maximal increase in IL-8, IL-6 and PGE-2 production and monolayer permeability was observed when using the cytokines simultaneously at their highest level, but this relied mainly on IL-1beta. The effects of TNF-alpha on IL-8 and IL-6 or NO production were stronger upon combination with IL-1beta or IFN-gamma, respectively, whereas cells were unaffected by the presence of LPS. Although NO production, induced by IFN-gamma-containing combinations, was observed only in differentiated cells, general inflammatory response was higher in proliferating cells. The use of a mixture of IL-1beta, TNF-alpha and IFN-gamma thus accurately mimics intestinal inflammatory processes, but cell differentiation and stimuli combination are important parameters to take into account for in vitro studies on intestinal inflammation. Copyright (c) 2010. Published by Elsevier Ltd.

Neuroendocrine Factors in the Regulation of Inflammation: Excessive Adiposity and Calorie Restriction

PubMed Central

Fontana, Luigi

2009-01-01

Acute inflammation is usually a self-limited life preserving response, triggered by pathogens and/or traumatic injuries. This transient response normally leads to removal of harmful agents and to healing of the damaged tissues. In contrast, unchecked or chronic inflammation can lead to persistent tissue and organ damage by activated leukocytes, cytokines, or collagen deposition. Excessive energy intake and adiposity cause systemic inflammation, whereas calorie restriction without malnutrition exerts a potent anti-inflammatory effect. As individuals accumulate fat and their adipocytes enlarge, adipose tissue undergoes molecular and cellular alterations, macrophages accumulate, and inflammation ensues. Overweight/obese subjects have significantly higher plasma concentrations of C-reactive protein and several cytokines, including IL-6, IL-8, IL-18, and TNF-alpha. Experimental animals on a chronic CR regimen, instead, have low levels of circulating inflammatory cytokines, low blood lymphocyte levels, reduced production of inflammatory cytokines by the white blood cells in response to stimulation, and cortisol levels in the high normal range. Recent data demonstrate that CR exerts a powerful anti-inflammatory effect also in non-human primates and humans. Multiple metabolic and neuroendocrine mechanisms are responsible for the CR-mediated anti-inflammatory effects, including reduced adiposity and secretion of pro-inflammatory adipokines, enhanced glucocorticoid production, reduced plasma glucose and advanced glycation end-product concentrations, increased parasympathetic tone, and increased ghrelin production. Measuring tissue specific effects of CR using genomic, proteomic and metabolomic techniques in humans will foster the understanding of the complex biological processes involved in the anti-inflammatory and anti-aging effects of CR. PMID:18502597

Nociceptor Sensitization Depends on Age and Pain Chronicity123

PubMed Central

Dodge, Amanda K.

2016-01-01

Abstract Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite the greater burden of chronic pain on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months old) and aged (>18 months old) mice exhibited prominent pain behaviors during both acute (2 day) and chronic (8 week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (AM) fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following two important findings: (1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury; and (2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive. PMID:26866058

Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers.

PubMed

Kraft, Birgit; Frickey, Nathalie A; Kaufmann, Rainer M; Reif, Marcus; Frey, Richard; Gustorff, Burkhard; Kress, Hans G

2008-07-01

Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia. The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing Delta-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain. Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered. To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.

Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity

PubMed Central

Liu, Yong; Chen, Xiao-Dong; Yu, Jiang; Chi, Jun-Lin; Long, Fei-Wu; Yang, Hong-Wei; Chen, Ke-Ling; Lv, Zhao-Ying; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

2017-01-01

Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis. PMID:28300832

Role of acute ethanol exposure and TLR4 in early events of sepsis in a mouse model

PubMed Central

Bhatty, Minny; Jan, Basit L; Tan, Wei; Pruett, Stephen B; Nanduri, Bindu

2011-01-01

Sepsis is a major cause of death worldwide. The associated risks and mortality are known to significantly increase on exposure to alcohol (chronic or acute). The underlying mechanisms of the association of acute ethanol ingestion and poor prognosis of sepsis are largely unknown. The study described here was designed to determine in detail the role of ethanol and TLR4 in the pathogenesis of the sepsis syndrome. The effects of acute ethanol exposure and TLR4 on bacterial clearance, spleen cell numbers, peritoneal macrophage numbers, and cytokine production were evaluated using wild type and TLR4 hypo-responsive mice treated with ethanol and then challenged with a non pathogenic strain of Escherichia. coli (E. coli). Ethanol treated mice exhibited a decreased clearance of bacteria and produced lesser amounts of most pro-inflammatory cytokines in both strains of mice at two hours after challenge. Neither ethanol treatment nor a hypo-responsive TLR4 had significant effects on the cell numbers in the peritoneal cavity and spleen 2 hours post infection. The suppressive effect of acute ethanol exposure on cytokine and chemokine production was more pronounced in the wild type mice, but the untreated hyporesponsive mice produced less of most cytokines than untreated wild type mice. The major conclusion of this study is that acute ethanol exposure suppresses pro-inflammatory cytokine production and that a hypo-responsive TLR4 (in C3H/HeJ mice) decreases pro-inflammatory cytokine levels but the cytokines and other mediators induced through other receptors are sufficient to ultimately clear the infection but not enough to induce lethal septic shock. In addition, results reported here demonstrate previously unknown effects of acute ethanol exposure on LIF (leukemia inhibitory factor) and eotaxin and provide the first evidence that IL-9 is induced through TLR4 in vivo. PMID:21872420

Timing of Bone Marrow Cell Delivery Has Minimal Effects on Cell Viability and Cardiac Recovery Following Myocardial Infarction

PubMed Central

Swijnenburg, Rutger-Jan; Govaert, Johannes A.; van der Bogt, Koen E.A.; Pearl, Jeremy I.; Huang, Mei; Stein, William; Hoyt, Grant; Vogel, Hannes; Contag, Christopher H.; Robbins, Robert C.; Wu, Joseph C.

2011-01-01

Background Despite ongoing clinical trials, the optimal time for delivery of bone marrow mononuclear cells (BMCs) following myocardial infarction (MI) is unclear. We compared the viability and effects of transplanted BMCs on cardiac function in the acute and sub-acute inflammatory phases of MI. Methods and Results The time-course of acute inflammatory cell infiltration was quantified by FACS analysis of enzymatically digested hearts of FVB mice (n=12) following LAD ligation. Mac-1+Gr-1high neutrophil infiltration peaked at day 4. BMCs were harvested from transgenic FVB mice expressing firefly luciferase (Fluc) and green fluorescent protein (GFP). Afterwards, 2.5×106 BMCs were injected into the left ventricle of wild-type FVB mice either immediately (Acute BMC) or 7 days (Sub-acute BMC) after MI, or after a sham procedure (n=8 per group). In vivo bioluminescence imaging (BLI) showed an early signal increase in both BMC groups at day 7, followed by a non-significant trend (P=0.203) towards improved BMC survival in the Sub-acute BMC group that persisted until the BLI signal reached background levels after 42 days. Compared to controls (MI + saline injection), echocardiography showed a significant preservation of fractional shortening at 4 weeks (Acute BMC vs saline; P<0.01) and 6 weeks (both BMC groups vs saline; P<0.05), but no significant differences between the two BMC groups. FACS analysis of BMC injected hearts at day 7 revealed that GFP+ BMCs expressed hematopoietic (CD45, Mac-1, Gr-1), minimal progenitor (Sca-1, c-kit), and no endothelial (CD133, Flk-1) or cardiac (Trop-T) cell markers. Conclusion Timing of BMC delivery has minimal effects on intramyocardial retention and preservation of cardiac function. In general, there is poor long-term engraftment and BMCs tend to adopt inflammatory cell phenotypes. PMID:19920031

Social Support, Heart Failure, and Acute Coronary Syndromes: The Role of Inflammatory Markers

DTIC Science & Technology

2008-04-03

APPROVAL SHEET MasterSDegrees Date Date J-t - L.l - O&, ’t -7- u ¥ 7Yt’A? Date Title of Dissertation: " Social Support, Heart Failure, and Acute Coronary...that the use of any copyrighted material in the thesis manuscript entitled: " Social Support, Heart Failure, and Acute Coronary Syndromes: The Role of...Department of Medical & Clinical Psychology Uniformed Services University Abstract Title of Thesis: “ Social Support, Acute Coronary Syndromes, and Heart

In vitro modulation of inflammatory target gene expression by a polyphenol-enriched fraction of rose oil distillation waste water.

PubMed

Wedler, Jonas; Weston, Anna; Rausenberger, Julia; Butterweck, Veronika

2016-10-01

Classical production of rose oil is based on water steam distillation from the flowers of Rosa damascena. During this process, large quantities of waste water accrue which are discharged to the environment, causing severe pollution of both, groundwater and surface water due to a high content of polyphenols. We recently developed a strategy to purify the waste water into a polyphenol-depleted and a polyphenol-enriched fraction RF20-(SP-207). RF20-(SP-207) and sub-fraction F(IV) significantly inhibited cell proliferation and migration of HaCaT cells. Since there is a close interplay between these actions and inflammatory processes, here we focused on the fractions' influence on pro-inflammatory biomarkers. HaCaT keratinocytes were treated with RF20-(SP-207), F(IV) (both at 50μg/mL) and ellagic acid (10μM) for 24h under TNF-α (20ng/mL) stimulated and non-stimulated conditions. Gene expression of IL-1β, IL-6, IL-8, RANTES and MCP-1 was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and cellular protein secretion of IL-8, RANTES and MCP-1 was determined by ELISA based assays. RF20-(SP-207) and F(IV) significantly decreased the expression and cellular protein secretion of IL-1β, IL-6, IL-8, RANTES and MCP-1. The diminishing effects on inflammatory target gene expression were slightly less pronounced under TNF-α stimulated conditions. In conclusion, the recovered polyphenol fraction RF20-(SP-207) from rose oil distillation waste water markedly modified inflammatory target gene expression in vitro, and, therefore, could be further developed as alternative treatment of acute and chronic inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of activated protein C on experimental acute necrotizing pancreatitis

PubMed Central

Yamenel, Levent; Mas, Mehmet Refik; Comert, Bilgin; Isik, Ahmet Turan; Aydin, Sezai; Mas, Nuket; Deveci, Salih; Ozyurt, Mustafa; Tasci, Ilker; Unal, Tahir

2005-01-01

Introduction Acute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis. Materials and method Forty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured. Results Acute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis factor--α, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively). Conclusion APC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis. PMID:15987389

Response of the periapical tissue of dogs' teeth to the action of citric acid and EDTA.

PubMed

Sperandio, Cristina Berthold; Silveira, Luiz Fernando Machado; de Araújo, Lenita Aver; Martos, Josué; Malshe, Ashwin

2008-01-01

The purpose of this study was to analyze the inflammatory response of dog's periapical tissues to 17% trisodium EDTA salt (pH 8.0) and 1% citric acid (pH 2.0). Saline was used as a control. Six adult dogs were used as the biological model of the study. The experimental units comprised 56 roots of mandibular molars (first and second) and premolars (first, second and third). After coronal opening, pulpectomy and root canal instrumentation were performed using the above-mentioned irrigating solutions. After 24 and 48 hours, the animals were euthanized and the teeth and their supporting tissues were removed and histologically processed. The sections were stained with hematoxylin and eosin and analyzed histopathologically with a light microscope at x100 magnification. The histological analysis focused on the occurrence of acute inflammatory response. The presence of swelling, vasodilatation and inflammatory cells were evaluated and the degree of inflammation was determined for each case. Data were analyzed by Fisher's exact test using the SPSS software with a confidence interval of 95% (p<0.05). 17% EDTA and 1% citric acid caused inflammatory responses in dog's periapical tissues with no significant differences to each other or to saline (control) at either the 24-hour (p=0.482) or 48-hour (p=0.377) periods. It may be concluded that the inflammatory response was of mild intensity for the tested substances.

Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy.

PubMed

Dominguez, Fernando; Kühl, Uwe; Pieske, Burkert; Garcia-Pavia, Pablo; Tschöpe, Carsten

2016-02-01

Myocarditis is defined as an inflammatory disease of the heart muscle and is an important cause of acute heart failure, sudden death, and dilated cardiomyopathy. Viruses account for most cases of myocarditis or inflammatory cardiomyopathy, which could induce an immune response causing inflammation even when the pathogen has been cleared. Other etiologic agents responsible for myocarditis include drugs, toxic substances, or autoimmune conditions. In the last few years, advances in noninvasive techniques such as cardiac magnetic resonance have been very useful in supporting diagnosis of myocarditis, but toxic, infectious-inflammatory, infiltrative, or autoimmune processes occur at a cellular level and only endomyocardial biopsy can establish the nature of the etiological agent. Furthermore, after the generalization of immunohistochemical and viral genome detection techniques, endomyocardial biopsy provides a definitive etiological diagnosis that can lead to specific treatments such as antiviral or immunosuppressive therapy. Endomyocardial biopsy is not commonly performed for the diagnosis of myocarditis due to safety reasons, but both right- and left endomyocardial biopsies have very low complication rates when performed by experienced operators. This document provides a state-of-the-art review of myocarditis and inflammatory cardiomyopathy, with special focus on the role of endomyocardial biopsy to establish specific treatments. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Elevated serum levels of endothelin-1 in patients with chronic inflammatory demyelinating polyneuropathy.

PubMed

Chang, Chun-Wei; Wu, Hsiu-Chuan; Lyu, Rong-Kuo; Lo, Yen-Shi; Chen, Chiung-Mei; Ro, Long-Sun; Chang, Hong-Shiu; Huang, Ching-Chang; Liao, Ming-Feng; Wu, Yih-Ru; Kuo, Hung-Chou; Chu, Chun-Che; Weng, Yi-Ching; Wei, Pei-Tsi; Lo, Ai-Lun; Chang, Kuo-Hsuan

2018-01-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, or non-hereditary, chronic demyelinating neuropathy. Currently, there is no reliable molecular biomarker that can identify CIDP patients as well as monitor disease severity. We measured serum levels of endothelin-1 (ET-1), a factors involved in vasoconstrictive, inflammatory and nerve regenerative processes, in 20 CIDP, 21 acute inflammatory demyelinating polyneuropathy (AIDP), 37 multiple sclerosis (MS), and 10 Alzheimer's disease (AD) patients, as well as 26 healthy control (HC) subjects. Patients with CIDP demonstrated higher serum levels of ET-1 (2.07±1.07pg/mL) than those with AIDP (0.75±0.62ng/mL, P<0.001), AD (0.78±0.49pg/mL, P<0.001), as well as HCs (1.16±0.63pg/mL, P=0.002), while levels of ET-1 in patients with MS (2.10±0.81pg/mL) and CIDP were similar. Furthermore, the serum ET-1 levels significantly correlated with Inflammatory Neuropathy Cause And Treatment (INCAT) disability scale in CIDP patients. Receiver operating characteristic (ROC) curve showed good discrimination ability for ET-1 to distinguish CIDP patients from AIDP (AUC=0.883) or HCs (AUC=0.763). This study discloses the potential of serum ET-1 as a biomarker for CIDP. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-inflammatory activity and chemical profile of Galphimia glauca.

PubMed

González-Cortazar, Manasés; Herrera-Ruiz, Maribel; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Marquina, Silvia; Alvarez, Laura; Tortoriello, Jaime

2014-01-01

Galphimia glauca, commonly known as "flor de estrella", is a plant species used in Mexican traditional medicine for the treatment of different diseases that have an acute or chronic inflammatory process in common. Aerial parts of this plant contain nor-seco-triterpenoids with anxiolytic properties, which have been denominated galphimines. Other compounds identified in the plant are tetragalloyl-quinic acid, gallic acid, and quercetin, which are able to inhibit the bronchial obstruction induced by platelet-activating factor. The objective of this work was to evaluate the anti-inflammatory effect of crude extracts from G. glauca and, by means of bioguided chemical separation, to identify the compounds responsible for this pharmacological activity. n-Hexane, ethyl acetate, dichloromethane, and methanol extracts showed an important anti-inflammatory effect. Chemical separation of the active methanol extract allowed us to identify the nor-seco-triterpenes galphimine-A (1) and galphimine-E (3) as the anti-inflammatory principles. Analysis of structure-activity relationships evidenced that the presence of an oxygenated function in C6 is absolutely necessary to show activity. In this work, the isolation and structural elucidation of two new nor-seco-triterpenes denominated as galphimine-K (4) and galphimine-L (5), together with different alkanes, fatty acids, as well as three flavonoids (17-19), are described, to our knowledge for the first time, from Galphimia glauca. Georg Thieme Verlag KG Stuttgart · New York.

Role of Quzhou Fructus Aurantii Extract in Preventing and Treating Acute Lung Injury and Inflammation.

PubMed

Li, Lili; Zhang, Sheng; Xin, Yanfei; Sun, Junying; Xie, Feng; Yang, Lin; Chen, Zhiqin; Chen, Hao; Liu, Fang; Xuan, Yaoxian; You, Zhenqiang

2018-01-26

Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro. In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.

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

Chen, Jing; Mo, Yiqun; Schlueter, Connie F.

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-inducedmore » neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.« less

[Cutaneous radiation syndrome after accidental skin exposure to ionizing radiation].

PubMed

Peter, R U

2013-12-01

Accidental exposure of the human skin to single doses of ionizing radiation greater than 3 Gy results in a distinct clinical picture, which is characterized by a transient and faint erythema after a few hours, then followed by severe erythema, blistering and necrosis. Depending on severity of damage, the latter generally occurs 10-30 days after exposure, but in severe cases may appear within 48 hrs. Between three and 24 months after exposure, epidermal atrophy combined with progressive dermal and subcutaneous fibrosis is the predominant clinical feature. Even years and decades after exposure, atrophy of epidermis, sweat and sebaceous glands; telangiectases; and dermal and subcutaneous fibrosis may be found and even continue to progress. For this distinct pattern of deterministic effects following cutaneous accidental radiation exposure the term "cutaneous radiation syndrome (CRS)" was coined in 1993 and has been accepted by all international authorities including IAEA and WHO since 2000. In contrast to the classical concept that inhibition of epidermal stem cell proliferation accounts for the clinical symptomatology, research of the last three decades has demonstrated the additional crucial role of inflammatory processes in the etiology of both acute and chronic sequelae of the CRS. Therefore, therapeutic approaches should include topical and systemic anti-inflammatory measures at the earliest conceivable point, and should be maintained throughout the acute and subacute stages, as this reduces the need for surgical intervention, once necrosis has occurred. If surgical intervention is planned, it should be executed with a conservative approach; no safety margins are needed. Antifibrotic measures in the chronic stage should address the chronic inflammatory nature of this process, in which over-expression TGF beta-1 may be a target for therapeutic intervention. Life-long follow-up often is required for management of delayed effects and for early detection of secondary malignancies, which must be searched for especially in the borderline areas between clinically symptomatic and asymptomatic skin.

Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

PubMed

Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

1981-12-01

PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

Anti-inflammatory evaluation and characterization of leaf extract of Ananas comosus.

PubMed

Kargutkar, Samira; Brijesh, S

2018-04-01

Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In the present study, the potential anti-inflammatory activity of A. comosus leaf extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to preliminary qualitative phytochemical analysis and quantitative estimations of flavonoids and tannins. The components present in ALE were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and proteinase activity were assessed. Its effect on secretion of pro-inflammatory cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced inflammatory rat model was examined. The preliminary qualitative phytochemical analysis revealed presence of flavonoids, phenols, tannins, carbohydrates, glycosides, and proteins in the extract. Total flavonoids and total tannins were 0.17 ± 0.006 mg equivalent of quercetin/g of ALE and 4.04 ± 0.56 mg equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4-hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid, whereas GC-MS analysis identified the presence of campesterol and ethyl isoallocholate that have been previously reported for anti-inflammatory activity. ALE showed significant inhibition of protein denaturation and proteinase activity and also controlled secretion of tumour necrosis factor-α, interleukin-1β and prostaglandins, as well as the generation of reactive oxygen species by activated macrophages. ALE also significantly decreased carrageenan-induced acute paw edema. The study, therefore, identified the components present in ALE that may be responsible for its anti-inflammatory activity and thus demonstrated its potential use against acute inflammatory diseases.

Studies on the pathogenesis of fever. III. The leucocytic origin of endogenous pyrogen in acute inflammatory exudates.

PubMed

KING, M K; WOOD, W B

1958-02-01

The evolution of an acute inflammatory exudate produced in rabbits by the intraperitoneal injection of saline has been described. Evidence has been presented that polymorphonuclear leucocytes release endogenous pyrogen into the cell-free fluid of the exudate. Leucocytes from such exudates have also been shown to release pyrogen into the surrounding medium during incubation in vitro at 37 degrees C. The results of parallel cytological studies have provided evidence which suggests that the leucocytes give up their pyrogen while functionally intact. These observations add further support to the hypothesis that polymorphonuclear leucocytes play a significant role in the pathogenesis of fever.

Relationship between production of acute-phase proteins and strength of inflammatory stimulation in rats.

PubMed

Kuribayashi, Takashi; Tomizawa, Misaki; Seita, Tetsurou; Tagata, Kazutoshi; Yamamoto, Shizuo

2011-07-01

The relationship between intensity of inflammatory stimulation and production of α(2)-macroglobulin (α2M) and α(1)-acid glycoprotein (AAG) in rats was investigated. Sprague-Dawley rats were injected with turpentine oil at doses of 0.05, 0.2 or 0.4 mL/rat. Serum levels of α2M, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were measured by enzyme-linked immunosorbent assay, and AAG was measured by single radial immunodiffusion. Peak serum levels of α2M and AAG in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. However, no significant differences were observed for peak serum levels of these acute-phase proteins between 0.2 and 0.4 mL/rat. Furthermore, peak serum levels of IL-6 and CINC-1 in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. Thus, the production of these acute-phase proteins has upper limits, even under increased strength of inflammatory stimulation in rats injected with turpentine oil.

Relationship between production of acute-phase proteins and strength of inflammatory stimulation in rats

PubMed Central

Kuribayashi, Takashi; Tomizawa, Misaki; Seita, Tetsurou; Tagata, Kazutoshi; Yamamoto, Shizuo

2011-01-01

The relationship between intensity of inflammatory stimulation and production of α 2-macroglobulin (α2M) and α 1-acid glycoprotein (AAG) in rats was investigated. Sprague-Dawley rats were injected with turpentine oil at doses of 0.05, 0.2 or 0.4 mL/rat. Serum levels of α2M, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were measured by enzyme-linked immunosorbent assay, and AAG was measured by single radial immunodiffusion. Peak serum levels of α2M and AAG in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. However, no significant differences were observed for peak serum levels of these acute-phase proteins between 0.2 and 0.4 mL/rat. Furthermore, peak serum levels of IL-6 and CINC-1 in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. Thus, the production of these acute-phase proteins has upper limits, even under increased strength of inflammatory stimulation in rats injected with turpentine oil. PMID:21669904

Zerumbone reduced the inflammatory response of acute lung injury in endotoxin-treated mice via Akt-NFκB pathway.

PubMed

Ho, Yung-Chyuan; Lee, Shiuan-Shinn; Yang, Ming-Ling; Huang-Liu, Rosa; Lee, Chien-Ying; Li, Yi-Ching; Kuan, Yu-Hsiang

2017-06-01

Zerumbone, a cyclic eleven-membered sesquiterpene, is the major component of the essential oil isolated from the wild ginger, Zingiber zerumbet. There are several beneficial pharmacological activities of zerumbone including anti-inflammatory, antioxidant, and anticancer activities. Acute lung injury (ALI) is an acute pulmonary inflammatory disorder with high morbidity and mortality rate. In present study, we aimed to investigate the protective effects and mechanisms of zerumbone on endotoxin, lipopolysaccharide (LPS)-induced ALI. Mice were pretreated with zerumbone at various concentrations for 30 min followed by intratracheal administration of LPS for 6 h. Pretreatment with zerumbone not only reduced leukocytes infiltration into the alveolar space but also inhibited lung edema in LPS-induced ALI. Decreased secretion of proinflammatory cytokines such as TNFα and IL-6 caused by LPS were reversed by zerumbone. LPS-induced expressions of proinflammatory mediators, iNOS and COX-2, were inhibited by zerumbone. In addition, NFκB activation and Akt phosphorylation were inhibited by zerumbone in LPS-induced ALI. All these results suggested that the protective mechanisms of zerumbone on endotoxin-induced ALI were via inhibition of Akt-NFκB activation. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-inflammatory and anti-oxidative effects of alpha-lipoic acid in experimentally induced acute otitis media.

PubMed

Tatar, A; Korkmaz, M; Yayla, M; Gozeler, M S; Mutlu, V; Halici, Z; Uslu, H; Korkmaz, H; Selli, J

2016-07-01

To investigate the anti-inflammatory, anti-oxidative and tissue protective effects, as well as the potential therapeutic role, of alpha-lipoic acid in experimentally induced acute otitis media. Twenty-five guinea pigs were assigned to one of five groups: a control (non-otitis) group, and otitis-induced groups treated with saline, penicillin G, alpha-lipoic acid, or alpha-lipoic acid plus penicillin G. Tissue samples were histologically analysed, and oxidative parameters in tissue samples were measured and compared between groups. The epithelial integrity was better preserved, and histological signs of inflammation and secretory metaplasia were decreased, in all groups compared to the saline treated otitis group. In the alpha-lipoic acid plus penicillin G treated otitis group, epithelial integrity was well preserved and histological findings of inflammation were significantly decreased compared to the saline, penicillin G and alpha-lipoic acid treated otitis groups. The most favourable oxidative parameters were observed in the control group, followed by the alpha-lipoic acid plus penicillin G treated otitis group. Alpha-lipoic acid, with its antioxidant, anti-inflammatory and tissue protective properties, may decrease the clinical sequelae and morbidity associated with acute otitis media.

Curcumin attenuated acute Propionibacterium acnes-induced liver injury through inhibition of HMGB1 expression in mice.

PubMed

Gu, Qiaoli; Guan, Honggeng; Shi, Qin; Zhang, Yanyun; Yang, Huilin

2015-02-01

Curcumin is a phenolic product isolated from the rhizome of Curcuma longa and has protective effects on inflammatory diseases. Here we investigated the protective effect of curcumin in acute Propionibacterium acnes (P. acnes)-induced inflammatory liver injury. C57BL/6 mice were primed with P. acnes followed by LPS challenge to induce fulminant hepatitis. Curcumin or vehicle control was administered perorally by gavage once daily starting 2days before P. acnes priming. We found that curcumin significantly improved mouse mortality. Then, to investigate the underlying mechanisms of curcumin in this acute inflammatory liver injury model, we primed C57BL/6 mice with P. acnes only. We found that curcumin treatment attenuated P. acnes-induced liver injury as evidenced by decreased production of ALT. In addition, curcumin treatment reduced the production of proinflammatory cytokines such as TNF-α and IFN-γ, accompanied by reduced hepatocyte apoptosis. Furthermore, curcumin treatment significantly reduced HMGB1 cytoplasmic translocation and expression by down-regulating acetylation of lysine. Taken together, our results suggest that curcumin protects mice from P. acnes-induced liver injury through reduction of HMGB1 cytoplasmic translocation and expression. Copyright © 2014 Elsevier B.V. All rights reserved.

Formononetin inhibited the inflammation of LPS-induced acute lung injury in mice associated with induction of PPAR gamma expression.

PubMed

Ma, Zhanqiang; Ji, Weiwei; Fu, Qiang; Ma, Shiping

2013-12-01

Formononetin has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of formononetin in acute lung injury induced by lipopolysaccharide (LPS) in mice. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and IL-6,were assayed by enzyme-linked immunosorbent assay method. Pathological changes of hung tissues were observed by HE staining. Peroxisome proliferator-activated receptor (PPAR)-γ gene expression was measured by real-time PCR. The data showed that treatment with the formononetin group markedly attenuated inflammatory cell numbers in the BALF, increased PPAR-γ gene expression and improved SOD activity and inhibited MPO activity. The histological changes of the lungs were also significantly improved by formononetin compared to LPS group. The results indicated that formononetin has a protective effect on LPS-induced acute lung injury in mice.

Clinical Significance of A Waves in Acute Inflammatory Demyelinating Polyradiculoneuropathy.

PubMed

Lakshminarasimhan, Sindhuja; Venkatraman, Chandramouleeswaran; Vellaichamy, Kannan; Ranganathan, Lakshminarasimhan

2018-05-25

A wave is a late response recognized during recording of F waves. Though they might be seen in healthy subjects, their presence assumes significance in a patient presenting with polyradiculoneuropathy. In this prospective study, 75 patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were enrolled. They were divided into two groups based on the presence or absence of A waves. Clinical features, electrophysiological parameters and extent of clinical recovery in short-term follow-up were analyzed. A waves were present in 49 out of 75 patients (65%). Most common pattern observed was multiple A waves. Prevalence of A waves was more in lower limb nerves than upper limb nerves. Occurrence of A waves correlated with the presence of conduction block. Patients with A waves had higher Hughes grade (P = 0.003) and lower Medical Research Council sum score at 6 weeks of follow-up (P = 0.04) as compared to patients without A waves. A waves are common in acute inflammatory demyelinating polyradiculoneuropathy form of Guillain Barre syndrome and are considered as a marker of demyelination. Long-term follow-up studies are required to ascertain their significance in prognostication and assessing recovery.

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice.

PubMed

Rahimian, Reza; Zirak, Mohammad Reza; Seyedabadi, Mohammad; Keshavarz, Mojtaba; Rashidian, Amir; Kazmi, Sareh; Jafarian, Amir Hossein; Karimi, Gholamreza; Mousavizadeh, Kazem

2017-09-01

Acute pancreatitis (AP) causes morbidity and mortality. The aim of the present study was to investigate the protective effect of tropisetron against AP induced by cerulein. Cerulein (50μg/kg, 5 doses) was used to induce AP in mice. Six hours after final cerulein injection, animals were decapitated. Hepatic/pancreatic enzymes in the serum, pancreatic content of malondialdehyde (MDA), pro-inflammatory cytokines and myeloperoxidase (MPO) activity were measured. Tropisetron significantly attenuated pancreatic injury markers and decreased the amount of elevated serum amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), MPO activities and pro-inflammatory cytokines levels caused by AP in mice. Tropisetron didn't affect the pancreatic levels of MDA. Our results suggest that tropisetron could attenuate cerulein-induced AP by combating inflammatory signaling. Further clinical studies are needed to confirm its efficacy in patients with AP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program.

DTIC Science & Technology

1999-12-01

1 alpha (MTP-la), macrophage inflammatory protein-2 (MIP-2), and acute phase reactive proteins ( Sabourin and Casillas, 1998; Casillas et ah, 1997...14. Sabourin , C.L.K., and R.P. Casillas. 1998. Inflammatory Gene Expression in Sulfur Mustard Exposed Mouse Skin. The Toxicologist, Vol. 42. 15

Atypical Rocky Mountain spotted fever with polyarticular arthritis.

PubMed

Chaudhry, Muhammad A; Scofield, Robert Hal

2013-11-01

Rocky Mountain spotted fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently, RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare. The purpose of this study is to describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands and to review the previously reported patients with rickettsial infection and inflammatory arthritis. An 18-year-old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on examination in addition to an erythematosus macular rash and occasional fever. Acute and convalescent serology demonstrated R rickettsi infection. She was successfully treated with doxycycline. Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with 8 previously reported patients, only 1 of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations.

Atypical Rocky Mountain spotted fever with polyarticular arthritis

PubMed Central

Chaudhry, Muhammad A.; Hal Scofield, R.

2017-01-01

Background Rocky Mountain Spotted Fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare Purpose Describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands, and to review the previously reported patients with rickettsial infection and inflammatory arthritis Patient An 18 year old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on exam as well as an erythematosus macular rash, and occasional fever. Acute and convalescent serology demonstrated Rickettsia rickettsi infection. She was successfully treated with doxycycline. Conclusion Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with eight previously reported patients, only one of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations. PMID:24157965

Anti-inflammatory, analgesic and antipyretic effects of Lepidagathis anobrya Nees (Acanthaceae).

PubMed

Richard, Sawadogo Wamtinga; Marius, Lompo; Noya, Somé; Innocent Pierre, Guissou; Germaine, Nacoulma-Ouedraogo Odile

2011-01-01

This study investigated the general acute, anti-inflammatory, analgesic and antipyretic effects of methanol extract of Lepidagathis anobrya Nees (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema in rats were used for the evaluation of general acute anti-inflammatory effects. Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were used to evaluate the analgesic and antipyretic activities respectively. The extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of 0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw and ear edemas in rats. In the analgesic and antipyretic tests, the extract has shown a significant inhibition of writhes and hyperpyrexia with all the doses used when compared to the untreated control group. These results clearly show the anti-inflammatory, analgesic and antipyretic effects of the methanol extract of Lepidagathis anobrya and give the scientific basis for its traditional use. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.

Acute Neuroinflammatory Response in the Substantia Nigra Pars Compacta of Rats after a Local Injection of Lipopolysaccharide.

PubMed

Flores-Martinez, Yazmin M; Fernandez-Parrilla, Manuel A; Ayala-Davila, Jose; Reyes-Corona, David; Blanco-Alvarez, Victor M; Soto-Rojas, Luis O; Luna-Herrera, Claudia; Gonzalez-Barrios, Juan A; Leon-Chavez, Bertha A; Gutierrez-Castillo, Maria E; Martínez-Dávila, Irma A; Martinez-Fong, Daniel

2018-01-01

Models of Parkinson's disease with neurotoxins have shown that microglial activation does not evoke a typical inflammatory response in the substantia nigra, questioning whether neuroinflammation leads to neurodegeneration. To address this issue, the archetypal inflammatory stimulus, lipopolysaccharide (LPS), was injected into the rat substantia nigra. LPS induced fever, sickness behavior, and microglial activation (OX42 immunoreactivity), followed by astrocyte activation and leukocyte infiltration (GFAP and CD45 immunoreactivities). During the acute phase of neuroinflammation, pro- and anti-inflammatory cytokines (TNF- α , IL-1 β , IL-6, IL-4, and IL-10) responded differentially at mRNA and protein level. Increased NO production and lipid peroxidation occurred at 168 h after LPS injection. At this time, evidence of neurodegeneration could be seen, entailing decreased tyrosine hydroxylase (TH) immunoreactivity, irregular body contour, and prolongation discontinuity of TH + cells, as well as apparent phagocytosis of TH + cells by OX42 + cells. Altogether, these results show that LPS evokes a typical inflammatory response in the substantia nigra that is followed by dopaminergic neurodegeneration.

Acute Neuroinflammatory Response in the Substantia Nigra Pars Compacta of Rats after a Local Injection of Lipopolysaccharide

PubMed Central

Gonzalez-Barrios, Juan A.; Gutierrez-Castillo, Maria E.

2018-01-01

Models of Parkinson's disease with neurotoxins have shown that microglial activation does not evoke a typical inflammatory response in the substantia nigra, questioning whether neuroinflammation leads to neurodegeneration. To address this issue, the archetypal inflammatory stimulus, lipopolysaccharide (LPS), was injected into the rat substantia nigra. LPS induced fever, sickness behavior, and microglial activation (OX42 immunoreactivity), followed by astrocyte activation and leukocyte infiltration (GFAP and CD45 immunoreactivities). During the acute phase of neuroinflammation, pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-4, and IL-10) responded differentially at mRNA and protein level. Increased NO production and lipid peroxidation occurred at 168 h after LPS injection. At this time, evidence of neurodegeneration could be seen, entailing decreased tyrosine hydroxylase (TH) immunoreactivity, irregular body contour, and prolongation discontinuity of TH+ cells, as well as apparent phagocytosis of TH+ cells by OX42+ cells. Altogether, these results show that LPS evokes a typical inflammatory response in the substantia nigra that is followed by dopaminergic neurodegeneration. PMID:29854828

Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets.

PubMed

Kim, J Y; Kawabori, M; Yenari, M 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.

Rare inflammatory diseases of the white matter and mimics of multiple sclerosis and related disorders.

PubMed

Tardieu, Marc; Deiva, Kumaran

2013-12-01

The spectra of white matter neuroinflammatory diseases and pathological processes inducing inflammatory lesions in the white matter of the central nervous system are wider in children than in adults. The definitions of multiple sclerosis (MS) and of the related clinically isolated syndromes (CIS) and acute disseminated encephalomyelitis (ADEM) have been recently revised leading to a new consensus definition. However, other entities with similarities to these diseases may also develop with monophasic or relapsing white matter inflammation. These conditions include congenital immunogenetic diseases (such as hemophagocytic lymphohistiocytosis), vasculitis, and autoantibody-mediated encephalopathies (Hashimoto encephalopathy, encephalitis with anti-N-methyl-D-aspartate receptor antibodies and neuromyelitis optica). Moreover, infectious diseases, such as Lyme disease, tumors (oligodendroglioma and lymphoma), and even genetic or metabolic diseases should also be considered if the clinical course of the disease does not follow the typical pattern for ADEM or MS. This short review describes these different entities and provides information for the differential diagnosis of inflammatory diseases of the white matter. Georg Thieme Verlag KG Stuttgart · New York.

The sterile inflammatory response

PubMed Central

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

2015-01-01

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. While 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. PMID:20307211

Role of the inflammasome in defense against venoms

PubMed Central

Palm, Noah W.; Medzhitov, Ruslan

2013-01-01

Venoms consist of a complex mixture of toxic components that are used by a variety of animal species for defense and predation. Envenomation of mammalian species leads to an acute inflammatory response and can lead to the development of IgE-dependent venom allergy. However, the mechanisms by which the innate immune system detects envenomation and initiates inflammatory and allergic responses to venoms remain largely unknown. Here we show that bee venom is detected by the NOD-like receptor family, pyrin domain-containing 3 inflammasome and can trigger activation of caspase-1 and the subsequent processing and unconventional secretion of the leaderless proinflammatory cytokine IL-1β in macrophages. Whereas activation of the inflammasome by bee venom induces a caspase-1–dependent inflammatory response, characterized by recruitment of neutrophils to the site or envenomation, the inflammasome is dispensable for the allergic response to bee venom. Finally, we find that caspase-1–deficient mice are more susceptible to the noxious effects of bee and snake venoms, suggesting that a caspase-1–dependent immune response can protect against the damaging effects of envenomation. PMID:23297192

Prostanoids and their receptors that modulate dendritic cell-mediated immunity.

PubMed

Gualde, Norbert; Harizi, Hedi

2004-08-01

Dendritic cells (DC) are essential for the initiation of immune responses by capturing, processing and presenting antigens to T cells. In addition to their important role as professional APC, they are able to produce immunosuppressive and pro-inflammatory prostanoids from arachidonic acid (AA) by the action of cyclooxygenase (COX) enzymes. In an autocrine and paracrine fashion, the secreted lipid mediators subsequently modulate the maturation, cytokine production, Th-cell polarizing ability, chemokine receptor expression, migration, and apoptosis of these extremely versatile APC. The biological actions of prostanoids, including their effects on APC-mediated immunity and acute inflammatory responses, are exerted by G protein-coupled receptors on plasma membrane. Some COX metabolites act as anti-inflammatory lipid mediators by binding to nuclear receptors and modulating DC functions. Although the role of cytokines in DC function has been studied extensively, the effects of prostanoids on DC biology have only recently become the focus of investigation. This review summarizes the current knowledge about the role of prostanoids and their receptors in modulating DC function and the subsequent immune responses.

Role of Macrophages in the Repair Process during the Tissue Migrating and Resident Helminth Infections

PubMed Central

Faz-López, Berenice

2016-01-01

The Th1/Th2/Th17 balance is a fundamental feature in the regulation of the inflammatory microenvironment during helminth infections, and an imbalance in this paradigm greatly contributes to inflammatory disorders. In some cases of helminthiasis, an initial Th1 response could occur during the early phases of infection (acute), followed by a Th2 response that prevails in chronic infections. During the late phase of infection, alternatively activated macrophages (AAMs) are important to counteract the inflammation caused by the Th1/Th17 response and larval migration, limiting damage and repairing the tissue affected. Macrophages are the archetype of phagocytic cells, with the primary role of pathogen destruction and antigen presentation. Nevertheless, other subtypes of macrophages have been described with important roles in tissue repair and immune regulation. These types of macrophages challenge the classical view of macrophages activated by an inflammatory response. The role of these subtypes of macrophages during helminthiasis is a controversial topic in immunoparasitology. Here, we analyze some of the studies regarding the role of AAMs in tissue repair during the tissue migration of helminths. PMID:27648452

Cecropia pachystachya: A Species with Expressive In Vivo Topical Anti-Inflammatory and In Vitro Antioxidant Effects

PubMed Central

Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira

2014-01-01

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β-carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms. PMID:24877079

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice.

PubMed

Rodrigues, Lindaiane Bezerra; Martins, Anita Oliveira Brito Pereira Bezerra; Ribeiro-Filho, Jaime; Cesário, Francisco Rafael Alves Santana; E Castro, Fyama Ferreira; de Albuquerque, Thaís Rodrigues; Fernandes, Maria Neyze Martins; da Silva, Bruno Anderson Fernandes; Quintans Júnior, Lucindo José; Araújo, Adriano Antunes de Sousa; Menezes, Paula Dos Passos; Nunes, Paula Santos; Matos, Isabella Gonçalves; Coutinho, Henrique Douglas Melo; Goncalves Wanderley, Almir; de Menezes, Irwin Rose Alencar

2017-11-01

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute cerebellar ataxia and infectious mononucleosis.

PubMed Central

Wadhwa, N. K.; Ghose, R. R.

1983-01-01

A 28-year-old man, who presented with acute cerebellar ataxia, was found to have haematological features of infectious mononucleosis. There was serological evidence of recent infection with Epstein-Barr virus. It is speculated that cerebellar dysfunction results from virus-induced inflammatory changes within the central nervous system. PMID:6312442

Critical role for CCAAT/Enhancer-binding protein beta in immune complex-induced acute lung injury

USDA-ARS?s Scientific Manuscript database

Although inflammation plays a central role in the pathogenesis of acute lung injury (ALI), the molecular mechanisms underlying inflammatory responses in ALI are poorly understood, and therapeutic options remain limited. The CCAAT/enhancer-binding protein (C/EBP) gamma and -gamma have been implicated...

Acute renal failure: unusual complication of Epstein-Barr virus-induced infectious mononucleosis.

PubMed

Lei, P S; Lowichik, A; Allen, W; Mauch, T J

2000-12-01

A 17-year-old boy with juvenile rheumatoid arthritis presented with jaundice, confusion, hemolytic anemia, thrombocytopenia, and acute renal failure secondary to titer-confirmed acute Epstein-Barr virus (EBV). Renal biopsy specimen revealed interstitial nephritis with an inflammatory infiltrate composed of cytotoxic/suppressor T cells, and interstitial mononuclear cell nuclei expressed EBV encoded RNA-1 (EBER-1) mRNA. Methylprednisolone treatment resulted in rapid improvement.

AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

PubMed Central

Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

2008-01-01

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

PubMed Central

Liu, Guangliang; Wang, Ruixue; London, Steven D.; London, Lucille

2013-01-01

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 107 pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation. PMID:23437361

Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

PubMed Central

Zdolsek, Johann; Eaton, John W; Tang, Liping

2007-01-01

Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age) were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing) plasma or (fibrinogen-free) serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior to, and shortly after, medical device implantation should improve the functionality and longevity of medical implants. PMID:17603911

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats

PubMed Central

Zhi, Jianming; Gustin, Pascal

2018-01-01

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness. PMID:29489916

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats.

PubMed

Zhao, Shiwei; Yang, Qi; Yu, Zhixi; Lv, You; Zhi, Jianming; Gustin, Pascal; Zhang, Wenhui

2018-01-01

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.