Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.
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PMID:Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin. 1513 69

Effective treatments to improve survivability following exposure to the nerve agent soman have been established and are currently available. Unfortunately, electrographic brain seizures, neuroinflammation and brain cell death are still a potential problem even with treatment. In the present study we have characterized the time course of the central neuro-inflammatory gene response using quantitative real time-PCR (TaqMan). Male Sprague-Dawley rats were pre-treated with HI-6 (1-2-hydroxy-iminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino-2-oxapropane dichloride); 125 mg/kg, i.p.) and exposed 30 min later to 1.6 x LD(50) of soman (pinacolyl methyl-phosphonofluoridate, 180 microg/kg, s.c.) followed at 1 min by atropine methyl nitrate (4 mg/kg, i.m.). Initially, a significant and dramatic upregulation of tumor necrosis factor-alpha and vascular cell adhesion molecule-1 mRNA levels was measured 2 h post-exposure followed at 6 h by upregulation of interleukin-1beta, interleukin-6, E-selectin, and intercellular adhesion molecule-1 with eventual resolution by 24-48 h. In conclusion, an acute and transient upregulation of the inflammatory gene response is activated following soman exposure that may be involved in the soman-induced brain injury process.
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PMID:Central neuro-inflammatory gene response following soman exposure in the rat. 1295 Nov 90

Current evidence suggests that tumor necrosis factor alpha (TNFalpha) and the family of interferons (IFNs) synergistically regulate many cellular responses that are believed to be critical in chronic inflammatory diseases, although the underlying mechanisms of such interaction are complex, cell-specific, and not completely understood. In this study, TNFalpha in a time-dependent manner activated both janus tyrosine kinase 1 and Tyk2 tyrosine kinase and increased the nuclear translocation of interferon-regulatory factor-1, STAT1, and STAT2 in human airway smooth muscle cells. In cells transfected with a luciferase reporter, TNFalpha stimulated gamma-activated site-dependent gene transcription in a time- and concentration-dependent manner. Using neutralizing antibodies to IFNbeta and TNFalpha receptor 1, we show that TNFalpha-induced secretion of IFNbeta mediated gamma-activated site-dependent gene expression via activation of TNFalpha receptor 1. In addition, neutralizing antibody to IFNbeta also completely abrogated the activation of interferon stimulation response element-dependent gene transcription induced by TNFalpha. Secreted IFNbeta acted as a negative regulator of TNFalpha-induced interleukin-6 expression, while IFNbeta augmented TNFalpha-induced RANTES (regulated on activation normal T cell expressed and secreted) secretion but had little effect on TNFalpha-induced intercellular adhesion molecule-1 expression. Furthermore TNFalpha, a modest airway smooth muscle mitogen, markedly induced DNA synthesis when cells were treated with neutralizing anti-IFNbeta. Together these data show that TNFalpha, via the autocrine action of IFNbeta, differentially regulates the expression of proinflammatory genes and DNA synthesis.
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PMID:Tumor necrosis factor alpha modulates airway smooth muscle function via the autocrine action of interferon beta. 1451 61

Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of a single viral agent and to correlate between cytokine levels and leukocytes. Cerebrospinal fluid samples, collected during an outbreak of echovirus type 4 meningitis in infants and children in Israel, were tested for routine characteristics. In addition, cytokine levels were measured in 71 meningitis patients and compared with those of 11 nonmeningitis patients. Concentrations of interleukin-6 (2417 +/- 2713 vs 28 +/- 20 pg/mL; P < 0.01) and interferon gamma (36 +/- 38 vs 4.8 +/- 0.9 pg/mL; P < 0.01) were significantly higher in patients with meningitis than in the control group, whereas soluble intercellular adhesion molecule-1 (1.12 +/- 2.6 vs 0.06 +/- 0.1 ng/mL) levels did not differ significantly. In addition, only interleukin-6 levels correlated with leukocyte counts in viral meningitis patients. Interleukin-6 was the most sensitive and specific characteristic in predicting meningitis in this homogeneous group of patients. Furthermore, only interleukin-6 correlated with leukocyte counts in the cerebrospinal fluid.
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PMID:Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis. 1464 93

The onset of cerebral ischaemia triggers a cascade of proinflammatory molecular and cellular events. Clinical studies suggest that the strength of this acute response is important in early and late clinical outcomes, early clinical worsening, and extent of brain damage. Variables that are predictors of adverse stroke outcome include erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1. Current data indicate that inflammation serves to fuel atherosclerosis and can act as the link between atherosclerosis and atherothrombosis. Growing evidence indicates that platelets act as prominent players in the inflammatory component of these disease processes. Thus, upon activation, platelets release a series of cytokines and growth factors and express CD40 ligand, which interacts with the CD40 receptor on other major cell types involved in atherosclerosis/atherothrombosis. In healthy volunteers, CD40L expression in platelets is not significantly inhibited by acetylsalicylic acid (ASA) alone, but is inhibited after treatment with the ADP-receptor antagonist clopidogrel or with clopidogrel plus ASA. Of a range of potential inflammatory biomarkers that have been reported in the literature, the best studied is CRP. Such biomarkers may have clinical utility for refined identification of patients at high risk for atherothrombosis in different arterial beds and for monitoring of therapeutic agents in clinical trials.
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PMID:Role of inflammation in stroke and atherothrombosis. 1473 Feb 51

Oxidized low-density lipoprotein (LDL) is believed to play a key role in the development of atherosclerosis. However, the significance of anti-oxidized LDL antibody in atherogenesis is unclear. The purposes of this study were to assess whether anti-oxidized LDL antibody titers are related to other inflammatory markers of possible interest in atherosclerotic development, such as soluble cell adhesion molecules, interleukin-6, and C-reactive protein (CRP), and to determine the prognostic value of anti-oxidized LDL antibody as a predictor of cardiac events in patients with unstable angina pectoris. Sixty patients (35 men and 25 women; mean age 60 years) with unstable angina were included in this study. The levels of CRP and of intercellular adhesion molecule-1 (ICAM-1) at 24 and 72 hours after admission were significantly higher than their baseline levels (p <0.05, respectively). After adjusting for age, gender, body mass index, and statin use, anti-oxidized LDL antibodies were positively correlated with CRP (r = 0.72, p <0.001) and ICAM-1 (r = 0.68, p <0.001). Elevated anti-oxidized LDL antibodies (mean >11.37 U/ml) and CRP levels (median >2.4 mg/L) on admission were correlated with a significantly lower 16-month, event-free survival rate (Kaplan-Meier event-free survival analysis, log-rank p <0.01 and p <0.05, respectively). Multivariate analysis by logistic regression revealed that elevated levels of anti-oxidized LDL antibody (mean >11.3 U/ml) on admission were an independent risk factor for an adverse cardiac event (odds ratio 2.2, 95% confidence interval 1.5 to 10.7, p = 0.001). This study demonstrates that anti-oxidized LDL antibody expression is associated with the expression of CRP and adhesion molecules, especially ICAM-1, and is a predictor of cardiac events in patients with unstable angina pectoris. The observed elevated levels of anti-oxidized LDL antibody suggest plaque instability and may be useful for identifying patients at higher risk of a cardiac event.
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PMID:Associations among oxidized low-density lipoprotein antibody, C-reactive protein, interleukin-6, and circulating cell adhesion molecules in patients with unstable angina pectoris. 1499 78

There is evidence that moderate consumption of red wine with its high content of polyphenolic antioxidants may be more protective than white wine against development of coronary artery disease (CAD). The aim of this study was to compare the acute effects of ingestion of red wine and white wine on markers of inflammation in men with CAD. Thirteen men with angiographically-proven CAD were studied in a cross-over trial. The men consumed 4 mL/kg (2 to 3 glasses) red wine and white wine in random order during a light meal and with at least a week between interventions. Later, the men also consumed an isoenergetic nonalcoholic beverage (control) in the same study protocol. Venous blood was taken at baseline, 1 hour, and 6 hours after the drinks. Plasma interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), blood alcohol, plasma lipids, and plasma polyphenols were measured. Mean +/- SD blood alcohol was 6.5 +/- 2.2 mmol/L and 6.9 +/- 1.1 mmol/L at 1 hour and returned to baseline at 6 hours after intake of red wine and white wine, respectively. Plasma IL-6 concentration increased significantly (P =.01) during 6 hours after ingestion of red wine (56%) and white wine (63%). The increase in plasma IL-6 concentration after ingestion of wine was significantly higher (P =.045) compared with the corresponding increase (11%) following intake of the nonalcoholic beverage. Plasma IL-6 levels at 6 hours (r =.631, P =.02) were correlated significantly with plasma alcohol levels at 1 hour after ingestion of red wine. These data suggest that moderate wine intake may acutely increase plasma levels of IL-6 in men with CAD. It is possible that this increase in plasma IL-6 is a response to alcohol-induced oxidative stress in the liver.
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PMID:Acute effect of drinking red and white wines on circulating levels of inflammation-sensitive molecules in men with coronary artery disease. 1501 43

Recent evidence suggests that CD38, an ectoenzyme that converts NAD(+) to cyclic ADP-ribose (cADPr), may play a role in cytokine-induced airway smooth muscle (ASM) cell hyper-responsiveness, a key feature associated with chronic asthma. In the present study, we investigated the major signaling pathways by which tumor necrosis factor-alpha (TNFalpha) induces CD38 expression and its role in regulating gene expression in human ASM cells. Using flow cytometry analyses, TNFalpha enhanced CD38 expression in a manner that was time-(0-24 h), concentration-(0.1-40 ng/ml), and protein synthesis-(cycloheximide blockade) dependent. A selective agonistic antibody against tumor necrosis factor receptor (TNFR) 1 also augmented CD38 expression, whereas anti-TNFR2 antagonistic antibody did not prevent the TNFalpha response. Inhibition of the Janus activated kinase/signal transducer and activator of transcription pathways using the soluble inhibitor 2-(1,1-dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz-[h]imidaz[4,5-f]isoquinolin-7-one (DBI) or with neutralizing antibody against interferon beta (IFNbeta) completely abrogated TNFalpha-induced CD38 expression at both protein and mRNA levels. Combining TNFalpha (0.1 and 1 ng/ml) and IFNbeta (100 IU/ml) at concentrations alone that had little effect on CD38 expression induced a robust synergistic induction of CD38 mRNA and protein levels. 8-Bromo-cADPr, a cADPr antagonist, significantly augmented TNFalpha-induced interleukin-6 secretion, whereas regulated on activation normal T cell expressed and secreted secretion was suppressed. 8-Bromo-cADPr, however, did not affect TNFalpha-induced cell surface expression of intercellular adhesion molecule-1. Our study is the first to demonstrate that IFNbeta-dependent activation of CD38 pathway is a novel component by which TNFalpha differentially regulates the expression of inflammatory genes in ASM cells.
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PMID:Tumor necrosis factor-alpha differentially regulates the expression of proinflammatory genes in human airway smooth muscle cells by activation of interferon-beta-dependent CD38 pathway. 1526 23

Atherogenic cofactors, such as altered cholesterol metabolism, may impact locally on inflammatory responses in atherosclerotic lesions. Blood levels of inflammatory markers (e.g., C-reactive protein, fibrinogen) have been associated with hypercholesterolemia and with overt atherothrombotic disorders. More recently. cytokines (e.g., interleukin-6, interleukin-1beta) and soluble adhesion molecules (e.g., selectins, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) have been associated with both hypercholesterolemia and atherosclerotic disease, suggesting their use as potential therapeutic targets for the non-specific "anti-inflammatory" treatment of atherosclerosis. The inflammatory response associated with hypercholesterolemia involves not only the intrinsic cells of the artery wall. but also circulating cells. Platelets participate in this disease process through the release of a wide variety of biologically active substances. An imbalance of the hemostatic system and persistent in vivo platelet activation can be observed in hypercholesterolemia and may have pathophysiological implications in the development and progression of atherosclerotic plaques. Recent findings on the inflammatory actions of platelets have established the potential for a previously unrecognized biologic role for platelets in inflammation and vascular injury, and have opened new perspectives in the comprehension of the pathogenetic mechanism(s) of atherosclerosis. Stimulated platelets actively synthesize proinflammatory cytokines (e.g., CD40L, IL-1beta) and are able to release chemokines (i.e., platelet factor-4, RANTES) which have been all involved in the inflammatory process associated with hypercholesterolemia. This review will summarize the present understanding of the interplay between hypercholesterolemia, inflammation and platelet activation in the development and progression of atherosclerosis, and we also discuss the effects of lipid-lowering treatment on these phenomena.
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PMID:Platelet activation, inflammatory mediators and hypercholesterolemia. 1532 Aug 41

The aim of current study is to investigate the effect of systemic administration of lipopolysaccharide (LPS) on the temporal pattern of cortical nuclear factor kappa B (NF-kappaB) binding activity, inflammatory response and secondary damage in the injured brain following traumatic brain injury (TBI). Right parietal cortical contusion in rats was made by using weight-dropping method. The rats were randomly divided into sham, LPS, TBI and TBI-LPS groups, with LPS injected intraperitoneally. NF-kappaB binding activity, cytokines, intercellular adhesion molecule-1 (ICAM-1) and brain damage were detected by electrophoretic mobility shift assay (EMSA), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labeling (TUNEL) apoptosis, respectively. The results showed that systemic administration of LPS following TBI could induce an immediate, strong and persistent upregulation of NF-kappaB, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and ICAM-1 in the area surrounding the injured brain. As compared with rats of sham, LPS and TBI groups, NF-kappaB binding activity, TNF-alpha and IL-6 were significantly upregulated in the surrounding cortex of injured site as early as 3 h postinjury when challenged with LPS, kept at high level up to 7-days postinjury. ICAM-1-positive vessels and apoptotic TUNEL-positive cells in the injured brain were also significantly increased in TBI-LPS rats. It was concluded that inflammatory response and secondary brain damage occurred in the injured brain could be highly exacerbated by endotoxemia.
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PMID:Effect of systemic LPS injection on cortical NF-kappaB activity and inflammatory response following traumatic brain injury in rats. 1547 94


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