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)

Increased levels of fibrin D-dimer are indicative of a hypercoagulable state, as found in acute coronary syndromes. Few well-controlled studies have assessed D-dimers in patients with stable coronary artery disease (CAD). We measured levels of D-dimers (in ng/mL by enzyme-linked immunosorbent assay) in 312 patients with angiographically proved CAD and stable angina pectoris and in 477 age- and sex-matched healthy blood donors. Demographic characteristics were assessed by a standardized questionnaire, and a complete lipid profile was performed for all subjects. In addition, a variety of other markers of hemostasis and inflammation were measured. The distribution of D-dimer levels was skewed to the right, and plasma median levels were higher in cases than in controls (median: 11.2 vs 2.8 ng/mL; P<0.001). In controls, correlations of D-dimer were found with fibrinogen, plasma viscosity, and interleukin-6. In logistic regression analysis, the age- and sex-adjusted odds ratio (OR) for the presence of CAD was 2.6 (95% confidence interval [CI], 1.9 to 3.5) when the highest quartile of the D-dimer distribution was compared with the combined lower 3 quartiles. The OR did not change appreciably after controlling for nonlipid risk factors (OR, 2.7; 95% CI, 1.9 to 3.9) and remained significant after further adjustment for other hemostatic parameters (OR, 2.4; 95% CI, 1.7 to 3.3) and markers of inflammation (OR, 2.1; 95% CI, 1.5 to 2.9). Plasma D-dimer levels are strongly and independently associated with the presence of CAD in patients with stable angina pectoris. These results support the concept of a contribution of intravascular fibrin to atherothrombogenesis.
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PMID:Plasma fibrin D-dimer levels and risk of stable coronary artery disease: results of a large case-control study. 1159 48

Inflammatory cytokines play important roles in coronary artery disease. We investigated the clinical significance of monocyte-related cytokine expression in patients with angina pectoris. We studied 26 patients with stable effort angina and 20 patients with unstable angina in whom stenotic lesions of the coronary arteries were confirmed by selective coronary angiography. Plasma levels of interleukin-6 (IL-6), macrophage colony stimulating factor (MCSF), and monocyte chemoattractant protein-1 (MCP-1) were measured. Plasma levels of IL-6, MCSF, and MCP-1 in patients with unstable angina were significantly higher than those in patients with stable angina or control subjects. Patients with unstable angina were further divided into sub-groups according to their clinical classification; Levels of IL-6, MCSF, and MCP-1 in patients, who had anginal attacks at rest within the 48 h prior to admission (Braunwald class IIIB) were significantly higher than those in patients, who did not have attacks at rest (class IB). Five unstable patients, who were refractory to medical therapy and were referred for emergency coronary revascularization showed marked elevation of plasma MCSF and MCP-1 levels. In conclusion, plasma levels of monocyte-related cytokines were elevated in unstable angina. These increases were marked in patients with unstable angina with recent ischemic attack at rest, suggesting that activation of monocytes is involved in vulnerability of underlying atheromatous plaque.
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PMID:Increased levels of monocyte-related cytokines in patients with unstable angina. 1188 24

Interleukin-6 (IL-6) is a key molecule in chronic inflammation and has been implicated in the progression of atherosclerosis. HMG-CoA reductase inhibitors (statins) may reduce the cardiovascular risk and vulnerability of atherosclerotic plaque through nonlipid as well as lipid-lowering mechanisms, but their anti-inflammatory effects on the vascular tissue have not been fully elucidated. We investigated the effects of fluvastatin on IL-6 synthesis in human vascular smooth muscle cells (VSMCs). Addition of fluvastatin decreased IL-6 synthesis in VSMCs in a time (0-24 hours)- and dose (10(-8)-10(-5) mol/L)-dependent manner. Fluvastatin also decreased IL-6 mRNA expression in VSMCs. The effects of fluvastatin on IL-6 expression were completely reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not squalene. Inhibition of Rho by C3 exoenzyme or Rho kinase by Y-27632 significantly decreased IL-6 expression in VSMCs. In conclusion, fluvastatin decreases IL-6 synthesis in human VSMCs through inhibition of Rho pathway. These findings suggested that reduction of IL-6 expression by statins may partially explain their therapeutic effects in patients with coronary artery disease.
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PMID:HMG-CoA reductase inhibitors reduce interleukin-6 synthesis in human vascular smooth muscle cells. 1209 Sep 4

Administration of adenovirus (Ad) vectors to animals induces innate immune responses, typified by elevated interleukin-6 (IL-6). To assess innate responses to Ad vectors in humans, we evaluated serum IL-6 following administration of E1(-) E3(-) Ad vectors to different human hosts and the relationship among peak IL-6 and peak anti-Ad neutralizing antibodies. We administered: 1) Ad(GV)CFTR.10, a vector carrying the normal human CFTR cDNA (3 x 10(7) to 2 x 10(10) particle units (pu)) to airways of individuals with cystic fibrosis (CF); 2) Ad(GV)VEGF121.10, a vector carrying the normal human vascular endothelial growth factor (VEGF)121 cDNA, to the myocardium (4 x 10(8) to 4 x 10(10) pu) of individuals with coronary artery disease (CAD) and to lower extremity muscles (4 x 10(8) to 4 x 10(9.5) pu) of individuals with peripheral vascular disease (PVD); and 3) Ad(GV)CD.10, a vector carrying the Escherichia coli cytosine deaminase gene to skin (7 x 10(7) to 7 x 10(9) pu) and airways (7 x 10(8) to 7 x 10(10) pu) of normal individuals and to liver metastasis (4 x 10(8) to 4 x 10(9) pu) of individuals with colon carcinoma. IL-6 increased mildly (up to 220 pg/ml) following vector administration to skin and lung airways of normal individuals and of individuals with CF, and to muscle and liver metastasis of individuals with PVD and colon cancer, respectively. IL-6 responses were higher (up to 1100 pg/ml) following myocardial administration. Control individuals who had chest surgery and bronchoscopy, but no vector administration, had comparable IL-6 increases. Thus, both administration of Ad vectors of humans up to 10(10) pu and the procedures used to administer the vectors elicit systemic IL-6 responses. There was no correlation among peak IL-6 and peak anti-Ad antibodies. These observations indicate that the innate host responses following administration of Ad vectors to humans may result from the procedures used to administer the vector, and from the vector per se.
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PMID:Systemic interleukin-6 responses following administration of adenovirus gene transfer vectors to humans by different routes. 1234 28

Inflammation and smoking are associated with risk of cardiovascular disease, but not much is known yet about their relationship. We studied in 15 smoking and 15 nonsmoking patients with coronary artery disease (CAD) and in 15 smoking and 15 nonsmoking healthy subjects the relationships with the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). IL-6 and TNF-alpha were significantly higher in patients than in controls, both in smokers and in nonsmokers. Smoking only had a significant effect on IL-6, and mainly in the controls. In conclusion, inflammation is affected by both smoking and cardiovascular disease.
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PMID:The association between inflammation markers, coronary artery disease and smoking. 1261 81

Thrombopoietin (TPO) is the major regulator of platelet production. Plasma levels of TPO are thought to be regulated by its binding to platelets and megakaryocytes. Here we have used a model of cardiac surgery with cardiopulmonary bypass (CBP) to test the possibility that changes in TPO levels are influenced by the presence of coronary artery disease (CAD) and by changes in interleukin-6 (IL-6). After surgery patients with CAD (n = 22) or with normal coronary arteries (n = 11) showed a significant thrombocytopaenia followed by a reactive thrombocytosis. The platelet recovery was preceded by a significant rise in TPO (from 62.6 +/- 9.4 pg/ml at baseline to 129.2 +/- 19 pg/ml at 60 h, P <0.001), which in turn was preceded by, and was positively correlated with, a marked increase in circulating IL-6 (from 1.5 +/- 0.3 pg/ml at baseline to 269.3 +/- 30.6 pg/ml at 3-12 h, P <0.001). The rise of both IL-6 and TPO was significantly larger in patients with CAD. No correlation was found between the post-operative drop in platelet mass and changes in either the TPO or IL-6 levels. These findings suggest that in man circulating TPO levels, besides being controlled by changes in platelet mass, are influenced by inflammatory processes, including the presence of coronary atherosclerosis.
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PMID:Rise of circulating thrombopoietin following cardiothoracic surgery is potentiated in patients with coronary atherosclerosis: correlation with a preceding increase in levels of interleukin-6. 1262 39

A growing body of evidence supports the hypothesis that C-reactive protein (CRP) is a marker of inflammation in coronary artery disease. The purpose of the present study was to test the hypothesis that CRP correlates with macrophage accumulation during the initial stages of coronary vascular disease. Adult male pigs were fed a normal chow (NF) or a high-fat high-cholesterol (HF) diet for 20 wk. After 20 wk, blood was collected for analyses of interleukin-6 (IL-6), CRP, and lipids. After blood collection, the pigs were euthanized and the right coronary arteries (RCA) were harvested and fixed in neutral buffered formalin. Paraffin-embedded sections of RCA were stained immunohistochemically for CRP, scavenger receptor A (SRA), and monocyte chemoattractant protein-1 (MCP-1). All cholesterol fractions were elevated in the HF vs. the NF group (P < 0.05). There was little or no positive staining for CRP, SRA, or MCP-1 in the RCA of NF pigs, but there was extensive staining in lipidladen macrophage foam cells in the HF pigs. Double staining revealed colocalization of CRP with SRA and CRP with MCP-1 in foam cells. Serum IL-6 was below the assay detection limit in all pigs. Serum CRP correlated directly with plasma total cholesterol (R = 0.727, P = 0.041) and accumulation of SRA-positive macrophages (R = 0.938, P < 0.001) in RCA of HF pigs. We conclude that serum CRP correlates with macrophage accumulation and coronary artery disease in hypercholesterolemic pigs.
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PMID:C-reactive protein correlates with macrophage accumulation in coronary arteries of hypercholesterolemic pigs. 1275 76

The aim of this study was to determine whether patients with coronary artery disease (CAD) and concomitant peripheral arterial disease (PAD) have a greater inflammatory status than those with CAD alone. To this aim, we evaluated PAD (ankle/brachial pressure index <0.9), and measured plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6) and the soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in 234 patients who underwent coronary angiography. Median levels of CRP, IL-6 and sICAM-1 were higher in the CAD without PAD (n=134) and CAD+PAD (n=40) groups than in 60 patients without either disease ("controls"). Median CRP values were higher in patients with CAD+PAD than in patients with CAD alone (4.7 mg/L [1.5; 7.6] vs 2.4 mg/L [0.9; 3.8], p < 0.01).Three-vessel CAD was diagnosed in 60% of CAD+PAD patients and in 21% (p< 0.01) of CAD only patients. After adjustment for confounding factors, only PAD was independently associated with three-vessel CAD (p<0.001). This association was maintained after adjustment for IL-6, the only inflammatory parameter significantly associated with three-vessel CAD at univariate analysis (p<0.01). In conclusion, in CAD the coexistence of PAD is associated with a greater inflammatory status and more widespread coronary atherosclerosis. These results could help to explain the high cardiovascular risk of patients with concomitant CAD and PAD and suggest that PAD be included among the variables used to identify CAD patients for further diagnostic evaluation.
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PMID:Increased inflammatory status and higher prevalence of three-vessel coronary artery disease in patients with concomitant coronary and peripheral atherosclerosis. 1278 19

The immunologic response in atherosclerosis involves not only intrinsic cells of the artery wall, but also circulating leukocytes, lymphocytes, and macrophages. Interaction of various arms of the immune response modulates plaque development and stability, and it is conceivable that immunologic effects of some cardiovascular therapies may contribute to their mechanism of benefit. The preponderance of data has accrued with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Statin effects, such as inhibition of T cell activation, tissue factor expression, or reduction of platelet hyperreactivity, may elicit beneficial effects in vitro and in vivo in patients with coronary artery disease. Moreover, aspirin may limit oxidation of lipoproteins and fibrinogen, and it may inhibit cytokine-induced nitric oxide synthase II expression. The hypothesis that selective inhibition of cyclooxygenase-2 (COX-2) may increase risk of myocardial infarction is controversial and may also be of questionable clinical significance. Finally, angiotensin-converting enzyme (ACE) inhibitors not only reduce proinflammatory mediators, such as interleukin-6, but also enhance the concentration of anti-inflammatory cytokines, such as interleukin-10. Because ACE is expressed at the shoulder region of atherosclerotic plaques, and ACE activity is enhanced in unstable plaques, ACE inhibition may also contribute to plaque stability. This article reviews the potential immunomodulatory potencies of aspirin, COX-2 inhibitors, statins, and ACE inhibitors as established pharmacotherapy in patients with coronary artery disease.
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PMID:Role of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors, angiotensin-converting enzyme inhibitors, cyclooxygenase-2 inhibitors, and aspirin in anti-inflammatory and immunomodulatory treatment of cardiovascular diseases. 1281 30

Cytokines are biologically active low molecular weight proteins that possess several endocrine and metabolic functions and are known products of the immune system and inflammation. Several of these cytokines were shown to be independent risk factors for cerebrovascular and coronary artery disease. Because visceral and subcutaneous adipose tissues are the major sources of cytokines (adipokines), increased adipose tissue mass is associated with alteration in adipokine production (eg, overexpression of tumor necrosis factor-a, interleukin-6, plasminogen activator inhibitor-1, and underexpression of adiponectin in adipose tissue). The proinflammatory status associated with these changes provides a potential link between insulin resistance and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and in type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-a, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function.
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PMID:Adipokines, inflammation, and the endothelium in diabetes. 1286 91


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