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)

Tumor necrosis factor (TNF) and interleukin-6 (IL-6) are pleiotropic cytokines produced by immune and nonimmune cells. Inappropriate expression and production of TNF and IL-6 is thought to be involved in the pathogenesis of numerous diseases, including atherosclerosis which leads to coronary heart disease, osteoporosis and Alzheimer's disease. Conversely, these disorders belong to the late complications of menopause and hormone replacement therapy (HRT) may successfully improve them. Several studies have shown that postmenopausal women show an enhanced expression of TNF and IL-6. On contrary, the use of hormone replacement therapy by postmenopausal women has been shown to down regulate this overexpression. Therefore, the mechanisms underlying the protective effects of HRT can also be attributed to its immunomodulating properties which seem to restore cytokine homeostasis in postmenopausal women.
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PMID:[Role of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in the pathogenesis of late complications of menopause. Effects of hormone replacement therapy on TNF and IL-6 expression]. 1612 93

Poor subjective well-being has been associated with increased coronary heart disease (CHD) morbidity and mortality in population-based studies and with adverse outcomes in existing CHD. Little is known about the mechanisms responsible for this association, but immune activity appears to be a potential pathway. Despite the growing evidence linking immune activity to subjective feelings, very few studies have examined patients with CHD, and the results are conflicting. We examined consecutive women patients hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We assessed depression, vital exhaustion, and self-rated health by questionnaires. Circulating levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) concentrations were determined. After controlling for potential confounding factors there was a significant positive correlation between IL-6 levels and vital exhaustion and poor self-rated health. The association between hsCRP and vital exhaustion and self-rated health was borderline significant. In contrast, the correlations between psychological factors and IL-1ra levels were weak and non-significant, as were the correlations between inflammatory markers and depression. Similar relationships between the inflammatory markers and the measures of psychological well-being were obtained when the latter ones were categorized into tertiles. In conclusion, inflammatory activity, assessed by IL-6 and hsCRP levels, was associated with vital exhaustion and self-rated health in CHD women. These findings may provide further evidence for a possible psychoneuroimmune link between subjective well-being and CHD. Our observations also raise the possibility that a cytokine-induced sickness response in CHD may be better represented by constructs of vital exhaustion and self-rated health than of depression.
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PMID:Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease. 1621 26

Evidence suggests that inflammatory parameters such as high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), serum amyloid-A (SAA) and fibrinogen (Fib) are associated with cardiovascular morbidity and mortality. In this study we investigated the association between LDL-cholesterol (LDL-C), lipid lowering drug therapy (LLD) and inflammatory markers in 436 subjects (age 64,2 +/- 4.1 yr, BMI 27,6 +/- 3,9 kg/m2) with coronary heart disease, participating in outpatient exercise groups for cardiac rehabilitation. In a subgroup analysis (n=229), we looked at the respective effects of physical activity (PA) alone and in combination with LLD. For the whole group the levels of inflammatory markers were: hs-CRP 0,31 +/- 0,4 mg/dl; IL-6 2,04 +/- 1,6 pg/ml; SAA 6,26 +/- 14 mg/l; Fib 381 +/- 97 mg/dl. Compared to patients without LLD, those with LLD showed modestly lower concentrations for CRP (-7%) and IL-6 (-12%), (p<0.05, respectively). In patients with an LDL-C < 100 mg/dl, CRP (-12%) and Fib (-8%) were significantly lower (p<0.05, respectively) than in patients with LDL-C > 100 mg/dl. Patients with a high level of PA (PA > or = 3 times/week) exhibited significantly lower values for CRP (-18%), Fib (-11%) and SAA (-37%) (p<0.01, respectively) than patients with a low level of PA (< or = 1 time/week). The combination of a high level of PA, and intake of LLD further reduced CRP (-37%) and SAA (-45%), with no additional decrease in Fib (-10%) (p<0.01, respectively) compared to patients with a low level of PA and taking LLD. The data from this cross-sectional study suggest that factors such as LLD, LDL-C (< 100 mg/dl), and a high level of physical activity are associated with lower levels of inflammatory markers in patients with coronary heart disease. Particularly with respect to CRP and SAA values, a high level of PA in combination with LLD, showed the most pronounced effects. The proof of causality of these findings should further be investigated in randomized controlled trials.
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PMID:Association between LDL-cholesterol, statin therapy, physical activity and inflammatory markers in patients with stable coronary heart disease. 1638 47

Socioeconomic position consistently predicts coronary heart disease; however, the biologic mechanisms that may mediate this association are not well understood. The objective of this study was to determine whether socioeconomic position (measured as educational level) is associated with inflammatory risk factors for coronary heart disease, including C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and P-selectin. The study sample included 2,729 participants (53.4% women; mean age, 62 +/- 10 years) from the US Framingham Offspring Study cohort who attended examination cycles 3 (1984-1987) and 7 (1998-2001) and provided educational attainment data. Inflammatory markers were measured in fasting serum samples. Multivariable linear regression analyses were performed, adjusting for potential confounders including age, sex, and clinical risk factors. In age- and sex-adjusted analyses, educational attainment was significantly inversely associated with C-reactive protein (p < 0.0001), interleukin-6 (p < 0.0001), soluble intercellular adhesion molecule-1 (p < 0.0001), and monocyte chemoattractant protein-1 (p = 0.0004). After further adjustment for clinical risk factors, educational level remained significantly associated with C-reactive protein (p = 0.0002), soluble intercellular adhesion molecule-1 (p = 0.01), and monocyte chemoattractant protein-1 (p = 0.01). In conclusion, educational attainment is associated with inflammatory risk factors for coronary heart disease. The association provides evidence suggestive of a biologic pathway by which socioeconomic position may predispose to coronary heart disease.
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PMID:Association of educational level with inflammatory markers in the Framingham Offspring Study. 1642 Dec 36

Lack of social integration predicts coronary heart disease mortality in prospective studies; however, the biological pathways that may be responsible are poorly understood. The specific aims of this study were to examine whether social networks are associated with serum concentrations of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Participants in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were eligible for inclusion in the study. Social networks were assessed using the Berkman-Syme Social Network Index (SNI). Concentrations of IL-6, CRP, sICAM-1 and MCP-1 were measured in fasting serum samples. Multivariable linear regression analyses were used to assess the association of social networks with inflammatory markers adjusting for potential confounders including age, smoking, blood pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and antihypertensive medication, diabetes, cardiovascular disease, depression and socioeconomic status. Results found that the SNI was significantly inversely associated with IL-6 in men (p=0.03) after adjusting for potential confounders. In age-adjusted analyses, social networks also were significantly inversely associated with IL-6 for women (p=0.03) and were marginally to modestly associated with CRP and sICAM-1 for men (p=0.08 and 0.02, respectively), but these associations were not significant in the multivariate analyses. In conclusion, social networks were found to be inversely associated with interleukin-6 levels in men. The possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation.
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PMID:Social networks and inflammatory markers in the Framingham Heart Study. 1644 67

Previous studies have shown an association between serum C-reactive protein (CRP) and cardiovascular disease (CVD) risk. The roles of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) are less well established. The aim of the present study was to analyze the associations of CRP, IL-6 and TNFalpha with incident coronary heart disease (CHD) events, CVD events, and total mortality. A random population sample, including men and women aged 25-64 years was examined in Finland in 1992. The sample size was 7,927 and 6,051 (76%) participated. The cohort was followed up until the end of 2001. During the follow-up, 151 incident CHD events, 205 CVD events and 183 deaths from any cause were observed. A stratified random subsample (n=313) was used as the comparison group. After adjustment for conventional CVD risk factors, CRP showed a significant association with CHD risk in men (HR=2.39, 1.08-5.28, comparing fourth quartile to the first quartile). This association remained significant after further adjustment for TNFalpha. TNFalpha also was a significant predictor of CHD among men, but the association was nonlinear (HR=2.21, 1.18-4.14 comparing the three upper quartiles to the first quartile). Further adjustment for CRP did not change this association substantially. Both CRP and TNFalpha predicted also all CVD events and total mortality among men. Among women the findings were nonsignificant. In conclusion, CRP and TNFalpha were significant, independent predictors of CHD and CVD events and total mortality among men. These findings provide further support to the important role of inflammation in the pathogenesis of CVD.
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PMID:C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study. 1652 64

The lack of social integration has predicted coronary heart disease morbidity and mortality in prospective observational studies; however, the biologic mechanisms by which this may occur are not well understood. The objective of this study was to determine whether social integration is associated with inflammatory risk factors for coronary heart disease, specifically C-reactive protein (CRP) and interleukin-6. The study participants (aged 70 to 79 years; 380 men and 425 women) were from the MacArthur Successful Aging Study, a longitudinal study of 3 community-based cohorts in the United States of older adults with relatively high physical and cognitive functioning at baseline (1988 to 1989). The plasma concentrations of interleukin-6 and CRP were assessed using a high-sensitivity enzyme-linked immunosorbent assay. Cross-sectional logistic regression analyses were performed. Multivariate adjusted analyses indicated that social integration was significantly inversely associated with CRP concentration in men after adjusting for age, race/ethnicity, smoking, alcohol consumption, physical activity, body mass index, cardiovascular disease, other major or chronic conditions, physical functioning, socioeconomic status, and depression (odds ratio 2.23, 95% confidence interval 1.05 to 4.76, for elevated CRP [>3.19 mg/L] in the least socially integrated quartile vs the most socially integrated quartile). No significant associations were found between social integration and interleukin-6 in men or either inflammatory marker in women. In conclusion, social integration was negatively associated with the plasma CRP concentration in men. These findings suggest a potential biologic mechanism for the observed associations between social integration and coronary heart disease in prospective studies. Differences may exist between women and men in the biologic pathways associated with social integration.
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PMID:Relation of social integration to inflammatory marker concentrations in men and women 70 to 79 years. 1656 7

It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal muscle. In addition, adiponectin counteracts the pro-inflammatory effects of TNF-alpha on the arterial wall and probably protects against the development of arteriosclerosis. In obesity, the pro-inflammatory effects of cytokines through intracellular signalling pathways involve the NF-kappaB and JNK systems. Genetic or pharmacological manipulations of these effectors of the inflammatory response have been shown to modulate insulin sensitivity in different animal models. In humans, it has been suggested that the improved glucose tolerance observed in the presence of thiazolidinediones or statins is likely related to their anti-inflammatory properties. Thus, it can be considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of pro-inflammatory factors involved in the pathogenesis of insulin resistance.
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PMID:Recent advances in the relationship between obesity, inflammation, and insulin resistance. 1661 57

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.
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PMID:Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period. 1671 19

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [OR(integral)] = 1.34, 95% confidence interval [CI] 1.10-1.63; OR(trabecular )= 1.25, 95% CI 1.02-1.53; OR(cortical )= 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.
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PMID:Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study. 1692 45


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