UNIPROT:P05231 - FACTA Search

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)

Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the relative contribution of adhesion molecules, including selectins and ICAM-1, in this pathogenetic process, the cutaneous passive Arthus reaction was examined in mice lacking E-selectin, P-selectin, or both L-selectin and ICAM-1 with anti-P- or E-selectin mAbs. Edema and hemorrhage were significantly reduced in P-selectin(-/-) mice compared with wild-type mice while they were not inhibited in E-selectin(-/-) mice. Combined E- and P-selectin blockade resulted in more significant reduction relative to L-selectin/ICAM-1(-/-) as well as P-selectin(-/-) mice. Remarkably, both E- and P-selectin blockade in L-selectin/ICAM-1(-/-) mice completely abrogated edema and hemorrhage. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells that expressed significant levels of P-selectin glycoprotein ligand-1. Similarly reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated partly with the decreased production of tumor necrosis factor-alpha and interleukin-6. The results of this study indicate that both endothelial selectins contribute predominantly to the Arthus reaction by regulating mast cell and neutrophil infiltration and that the full development of the Arthus reaction is mediated cooperatively by all selectins and ICAM-1.
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PMID:Relative contributions of selectins and intercellular adhesion molecule-1 to tissue injury induced by immune complex deposition. 1270 29

Stroke is the second most common cause of death in developed countries. Carotid plaque disruption and distal embolization of atheromatous debris are the most common pathogenic mechanisms for cerebral ischemia from carotid atherosclerotic disease. Morphologic composition of the atherosclerotic plaque, rather than the stenotic severity, appears to be central in determining the risk of both plaque rupture and subsequent thrombosis. Histologic features of vulnerable plaques include a large lipid core, a thin fibrous cap, intraplaque hemorrhage, and an increased number of inflammatory cells, mostly monocyte-macrophages. Due to the catastrophic implications of thrombus formation and embolization on the arterial plaque, detection before major neurologic events occur is now a major goal of cardiovascular clinicians and researchers. New detection imaging techniques such as intravascular thermography, optical coherence tomography, photonic spectroscopy, and elastography have been developed in order to document atherosclerotic lesion composition. This review will focus on the new possibilities under investigation for vulnerable atherosclerotic carotid plaque detection by means of the serologic markers of plaque instability. New markers, such as pregnancy-associated protein A, P-selectin, interleukin-6 and interleukin-12, metalloproteinases, lipoprotein(a), and oxidation products have been reviewed. Most of the promising serologic markers in this article are still in a nascent phase of development and remain to be validated in clinical settings. However, these biohumoral markers, and their potential combination of techniques, may hold promise for the future characterization of the vulnerable plaque and moreover of the vulnerable patient.
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PMID:[Unstable carotid plaque: biochemical and cellular marker of vulnerability]. 1284 77

There are no satisfactory data on circulating concentrations of inflammatory cytokines and their potential relationship with traditional and nontraditional atherosclerosis risk factors in a large healthy young population. The present study was conducted to examine, in 179 healthy families selected from the STANISLAS cohort, the association between interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), orosomucoid, haptoglobin, cell-adhesion molecules (ICAM-1, E-, L- and P-selectin) and lipid parameter concentrations. Age, BMI, white blood cells and tobacco consumption contributed to the variation of IL-6 concentrations. Age and tobacco contributed also to TNF-alpha variation. Taking into account potential covariates, we showed strong positive correlation between IL-6 and both inflammatory markers TNF-alpha and CRP in parents and in offspring (P<0.001). In parents, IL-6 was associated with ICAM-1 and L-selectin (P<0.01), while IL-6 and TNF-alpha predicted E-selectin in offspring only (0.001<P<0.01). Furthermore, IL-6 showed a strong negative relationship with apo A-1 and HDL-cholesterol in females only (P<0.001). This study demonstrated that in a large healthy family population, children included, levels of IL-6 are closely associated with traditional and non-traditional atherosclerosis risk factors. All these data are useful for defining the precise role of cytokines in atherosclerosis mechanisms in physiological conditions.
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PMID:IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. 1461 8

Platelets play an important role in the inflammatory response. In a nonrandomized comparison, we examined the effect of clopidogrel pretreatment on platelet inflammatory marker expression in patients undergoing percutaneous coronary intervention (PCI). Platelet expression of the inflammatory markers CD40 ligand (L) and CD62 P-selectin (P) and serum levels of interleukin-6 and CD40L were compared in patients pretreated (>24 hours before PCI) or not pretreated with clopidogrel. Blood samples were obtained before and after the procedure, and from 18 to 24 hours later. Marker expression in resting and adenosine diphosphate (ADP) (50 micromol/L) and thrombin receptor activating peptide (TRAP) (10 micromol/L) activated samples was quantified by flow cytometry. Serum CD40L and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay. Seventy-nine patients were recruited into the study. Forty-two percent were pretreated with clopidogrel for a median of 5 days (range 1 to 1,325). Clopidogrel pretreatment was associated with lower ADP-activated platelet CD40L expression in baseline and postprocedural samples. Similarly, platelet CD62P expression at all time points in ADP-activated and in baseline and postprocedural TRAP-activated samples was lower in patients pretreated with clopidogrel. These differences remained after multivariate adjustment between the groups. Serum CD40L levels increased from 2.13 +/- 2.37 ng/ml at baseline to 4.77 +/- 3.86 ng/ml at 18 to 24 hours after the procedure (p <0.0001). Similarly, serum IL-6 levels increased at 18 to 24 hours after the procedure (14.8 +/- 42.0 pg/ml before vs 25.5 +/- 36.0 pg/ml at 18 to 24 hours after the procedure, p <0.0001). Clopidogrel pretreatment did not affect serum IL-6 or CD40L levels. Thus, clopidogrel pretreatment reduces platelet inflammatory marker expression in patients undergoing PCI.
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PMID:Effect of clopidogrel pretreatment on inflammatory marker expression in patients undergoing percutaneous coronary intervention. 1501 68

Immune complex (IC)-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by various adhesion molecules. To assess the contribution of P-selectin glycoprotein ligand-1 (PSGL-1) and selectins in the pathogenetic process, the cutaneous reverse-passive Arthus reaction was examined in mice treated with monoclonal antibodies (mAb) to PSGL-1 or P- and/or E-selectin. Edema and hemorrhage were significantly reduced in mice treated with anti-P-selectin mAb compared with control mice while they were not inhibited in mice treated with anti-E-selectin mAb. It is remarkable that blocking PSGL-1 by mAb resulted in significant, further reduction in edema and hemorrhage compared with blocking anti-P- or anti-E-selectin. However, blockade of E- and P-selectins exhibited more significant reduction relative to PSGL-1 blockade. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells. Reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated with the decreased production of tumor necrosis factor alpha and interleukin-6. The results of this study indicate that PSGL-1 contributes to the Arthus reaction mainly as a ligand of P-selectin and partly as a ligand of E- and/or L-selectin by regulating neutrophil and mast-cell recruitment and that PSGL-1 would be a therapeutic target for human IC-mediated diseases.
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PMID:P-selectin glycoprotein ligand-1 is required for the development of cutaneous vasculitis induced by immune complex deposition. 1512 73

Atrial fibrillation (AF) is a major cause of morbidity and mortality from stroke due to thromboembolism from the fibrillating left atrium, including its appendage. We hypothesized that indexes of inflammation (as indicated by C-reactive protein and interleukin-6) and indexes of the prothrombotic state in AF that represent platelet activation (soluble P-selectin levels), endothelial damage or dysfunction (von Willebrand factor), coagulation (tissue factor and fibrinogen), and hemorrheology (plasma viscosity and hematocrit) would be related to the presence of thromboembolic predictors on transesophageal echocardiography in patients with long-term AF. To test this hypothesis, we recruited 37 patients with long-term AF who were receiving warfarin therapy with an international normalized ratio of > or =2.0 for > or =3 weeks before transesophageal echocardiography. Twenty-two patients had dense spontaneous echo contrast (SEC) visible in the left atrium or left atrial appendage, 10 had complex atheromatous plaque in the descending aorta, 11 had peak left atrial appendage velocities < or =0.2 m/s, and 3 had thrombus visible in the left atrial appendage. Twenty-eight patients had > or =1 transesophageal echocardiographic (TEE) risk factor for thromboembolism. Plasma levels of C-reactive protein (p = 0.03) and soluble P-selectin (p = 0.04) and hematocrit (p = 0.004) were higher among patients with AF with dense SEC than among those without. No significant associations were found for other TEE risk factors. Hematocrit was the only variable significantly associated with the presence of > or =1 TEE risk factor among patients with AF (p = 0.007) and the only independent associate of dense SEC after multivariate analysis (relative risk 1.4, 95% confidence interval 1.1 to 1.6) per 1% increase in hematocrit (p = 0.003, r(2) = 0.22). Although hematocrit was the only independent associate of dense SEC and > or =1 TEE risk factor, significant associations between dense SEC and the 2 indexes, C-reactive protein and soluble P-selectin, may indicate that mechanisms other than stasis are present with dense SEC. These observations support an "inflammatory hypothesis" in the pathogenesis of SEC that may have implications for thrombogenesis in AF.
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PMID:Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation. 1516 16

In recent years, it has become apparent that low-grade vascular inflammation plays a key role in all stages of the pathogenesis of atherosclerosis. Weight loss has been shown to improve blood inflammatory markers; however, it is unknown if weight-loss diets varying in macronutrient composition differentially affect inflammatory responses. The primary purpose of the present study was to compare a very-low-carbohydrate diet and a low-fat weight-loss diet on inflammatory biomarkers in overweight men. In a randomized cross-over design, 15 overweight men (body fat, >25%; body mass index, 34 kg/m2) consumed two experimental weight-loss diets for two consecutive 6-week periods: a very-low-carbohydrate diet (<10% energy via carbohydrate) and a low-fat diet (<30% energy via fat). Both the low-fat and the very-low-carbohydrate diets resulted in significant decreases in absolute concentrations of hsTNF-alpha (high-sensitivity tumour necrosis factor-alpha), hsIL-6 (high-sensitivity interleukin-6), hsCRP (high-sensitivity C-reactive protein) and sICAM-1 (soluble intercellular cell-adhesion molecule-1). There was no significant change in absolute sP-selectin (soluble P-selectin) concentrations after either diet. Normalized inflammatory values represented as the delta change per 1 kg reduction in body mass showed a significant difference between the two diets only for sP-selectin (P<0.05). In summary, energy-restricted low-fat and very-low-carbohydrate diets both significantly decreased several biomarkers of inflammation. These data suggest that, in the short-term, weight loss is primarily the driving force underlying the reductions in most of the inflammatory biomarkers.
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PMID:Weight loss leads to reductions in inflammatory biomarkers after a very-low-carbohydrate diet and a low-fat diet in overweight men. 1526 1

The aim of the present study was to investigate whether success or failure of direct-current cardioversion in patients with persistent atrial fibrillation may be related to indexes of inflammation (as indicated by C-reactive protein and interleukin-6, platelet activation [soluble P-selectin levels], endothelial damage/dysfunction [von Willebrand factor], coagulation cascade [tissue factor and fibrinogen], and rheology [plasma viscosity and hematocrit]). We found that C-reactive protein levels are a predictor of initial cardioversion success, although they failed to predict long-term outcome. Although inflammation may be associated with "permanence" of atrial fibrillation, indexes of platelet activation, endothelial damage/dysfunction, or coagulation showed no relation to the immediate and long-term (2-month) cardioversion outcome.
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PMID:Predictive value of indexes of inflammation and hypercoagulability on success of cardioversion of persistent atrial fibrillation. 1532 42

Ischemia-reperfusion (I/R) injury is associated with activation of coagulation and inflammation. Interestingly, various anticoagulants have been shown to reduce both coagulation and inflammation in animal models of kidney I/R injury. Fondaparinux is a synthetic pentasaccharide that selectively inhibits factor Xa (FXa) in the coagulation cascade. The aim of this study was to investigate the effect of fondaparinux in a lethal murine model of kidney I/R injury. A murine model of kidney I/R was established. In this model, we measured activation of the coagulation cascade and induction of inflammation. Administration of fondaparinux to I/R-injured mice reduced fibrin deposition in the kidney, reduced serum creatinine levels and increased survival from 0 to 44% compared with saline-treated control mice. Fondaparinux also reduced interleukin-6 and macrophage inflammatory protein-2 expression and decreased neutrophil accumulation in the injured kidneys. Finally, we showed that fondaparinux reduced thioglycollate-induced recruitment of neutrophils into the peritoneum and inhibited the binding of U937 cells to P-selectin in vitro. Our data suggest that fondaparinux reduces kidney I/R injury primarily by inhibiting the recruitment of neutrophils.
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PMID:The synthetic pentasaccharide fondaparinux reduces coagulation, inflammation and neutrophil accumulation in kidney ischemia-reperfusion injury. 1574 44

The aim of the study was to determine whether a short-term treatment with simvastatin or fenofibrate may result in beneficial anti-inflammatory and antithrombotic effects in patients with high risk of coronary artery disease. In a randomized, double-blind study, we compared markers of inflammation, thrombin formation and platelet activation in patients with LDL cholesterol >130 mg/dl assigned to receive simvastatin (40 mg/d; n=20) or micronised fenofibrate (160 mg/d; n=22) for 28 days. Simvastatin, but not fenofibrate, lowered C-reactive protein (CRP) by 32% on day 3 (p<0.001), while both drugs reduced CRP significantly on day 28. Interleukin-6, soluble CD40 ligand, and monocyte chemoattractant protein-1 levels decreased significantly (by 20 to 50%) in both treatment groups on days 3 and 28. Soluble cell adhesion molecules remained unchanged in both groups. Simvastatin and fenofibrate significantly lowered plasma concentrations of thrombin-antithrombin complexes on days 3 and 28, but not platelet beta-thromboglobulin (betaTG) levels. Soluble P-selectin was lowered only in the simvastatin group. The total amount of thrombin generated at the site of microvascular injury also declined (by about 30%) as early as after 3 days of fenofibrate or simvastatin therapy, whereas beta TG release was reduced only in the simvastatin group on days 3 and 28. All the effects were independent of the changes in lipid profiles. Our results suggest that statins and fibrates can exert antithrombotic and anti-inflammatory effects as early as after 3 days of therapy. However, in contrast to statins, fibrates have no influence on platelet function within one month of therapy.
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PMID:Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia. 1611 3

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