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)

HIV-associated lipodystrophy or lipoatrophy, unreported before the introduction of highly active antiretroviral therapy (HAART), was first described in 1998, and has a prevalence ranging from 18% to 83%. As in genetic lipodystrophy syndromes, fat redistribution may precede the development of metabolic complications (dyslipidemia, insulin resistance) in HIV-infected patients receiving HAART. The pathogenesis of HAART-associated lipodystrophy and metabolic syndrome is complex and a number of factors are involved, including direct effects of HAART on lipid metabolism, endothelial and adipocyte cell function, and mitochondria. Protease inhibitors are responsible for a decrease in cytoplasmic retinoic-acid protein-1, in low density lipoprotein-receptor-related protein and in peroxisome proliferator activated receptor type-gamma. Nucleoside reverse transcriptase inhibitors, and thymidine analogues, are responsible for mitochondrial dysfunction as demonstrated by a decrease in subcutaneous adipose tissue mitochondrial DNA content. Both phenomena are responsible for a decreased differentiation of adipocytes, increased levels of free fatty acids and lipoatrophy. The increased levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin-6 may further contribute in development of lipodystrophy. TNF-alfa activates 11-beta-hydroxysteroid dehydrogenase type-1, which converts inactive cortisone to active cortisol, resulting in increased lipid accumulation in adipocytes and insulin resistance. HAART drugs and inflammatory cytokines are associated with a decrease in adiponectin. The levels of adiponectin and adiponectin-to-leptin ratio correlate positively with insulin resistance in HIV-infected patients with lipodystrophy. HAART-associated metabolic syndrome is an increasingly recognized clinical entity. The atherogenic profile of this syndrome may increase the risk of cardiovascular disease even in young HIV-infected patients. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the incidence of lipodystrophy and related metabolic complications in HIV-infected patients receiving HAART.
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PMID:Visceral fat as target of highly active antiretroviral therapy-associated metabolic syndrome. 1762 54

Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. Both traditional, Framingham risk factors and inflammation-associated factors are involved in RA-associated atherosclerosis. Among imaging techniques, the early determination of common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and nitroglycerine-mediated vasodilation (NMD) may be useful to determine atherosclerosis and endothelial dysfunction. We and others found increased ccIMT and impaired FMD in RA patients. Among immunological and metabolic laboratory markers, anticyclic citrullinated peptide (anti-CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), Th0/Th1 T cells, homocysteine, dyslipidemia, decreased folate and vitamin B12 production, and impaired paraoxonase activity may all be involved in the development of vascular disease in RA. The early diagnosis of endothelial dysfunction and atherosclerosis, active immunosuppressive treatment, the use of drugs that control atherosclerosis, changes in sedentary lifestyle, and the close follow-up of RA patients may help to minimize cardiovascular risk in these individuals.
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PMID:Accelerated atherosclerosis in rheumatoid arthritis. 1789 98

In worldwide studies, interleukin-6 (IL-6) is implicated in age-related disturbances. The aim of the present report was to determine the possible association of IL-6 -174 C/G promoter polymorphism with the cytokine profile as well as with the presence of selected cardiovascular risk features. This was a cross-sectional study on Brazilian women aged 60 years or older. A sample of 193 subjects was investigated for impaired glucose regulation, diabetes, hypertension, and dyslipidemia. Genotyping was done by direct sequencing of PCR products. IL-6 and C-reactive protein were quantified by high-sensitivity assays. General linear regression models or the Student t-test were used to compare continuous variables among genotypes, followed by adjustments for confounding variables. The chi-square test was used to compare categorical variables. The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In a recessive model, mean waist-to-hip ratio, serum glycated hemoglobin and serum glucose were markedly lower in C homozygotes (P = 0.001, 0.028, and 0.047, respectively). In a dominant hypothesis, G homozygotes displayed a trend towards higher levels of circulating IL-6 (P = 0.092). Non-parametric analysis revealed that impaired fasting glucose and hypertension were findings approximately 2-fold more frequent among G homozygous subjects (P = 0.042 and 0.043, respectively). Taken together, our results show that the IL-6 -174 G-allele is implicated in a greater cardiovascular risk. To our knowledge, this is the first investigation of IL-6 promoter variants and age-related disturbances in the Brazilian elderly population.
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PMID:Association between the -174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women. 1799 65

Metabolic syndrome, also known as the insulin resistance syndrome (IRS), dysmetabolic syndrome or syndrome X, is a burgeoning global epidemic. This constellation of risk factors, namely glucose intolerance, hypertension, dyslipidemia (high triglyceride and low HDL cholesterol), central obesity, pro-inflammatory and prothrombotic state, culminating to the development of premature cardiovascular and renal disease, has significant impact on life expectancy, societal productivity and quality of life. The underlying mechanism of this complex syndrome remains to be elucidated. In recent years, light has been shed on the roles of neuroendocrine system and adipocytokines on the pathogenesis of IRS. In this review, we summarize the possible links between insulin and various hormones (growth hormones (GH), catecholamines, glucocorticoids and sex hormones), partly mediated through visceral adiposity and adipocytokines (notably adiponectin, leptin, resistin, visfatin, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6)) in the pathogenesis of this syndrome.
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PMID:The role of adipocytokines and neurohormonal dysregulation in metabolic syndrome. 1822 Jun 44

An increased amount of adipose tissue or its disproportionate distribution between central and peripheral body regions is related to the development of insulin resistance, type 2 diabetes mellitus, dyslipidemia, atherosclerosis, and coronary artery disease. Until recently, adipose tissue was regarded as a storage depot for lipids. It is now viewed as a hormonally active organ that plays a crucial metabolic role. The most important products of adipose tissue collectively referred to as adipocytokines, include adiponectin, leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), resistin, plasminogen-activating inhibitor-I (PAI-1), and angiotensinogen. These low and medium molecular weight proteins play an important role in the adipose tissue physiology and are believed to be a link between obesity, insulin resistance and endothelial dysfunction. This review describes the metabolic role of two of these proteins, adiponectin and leptin, in relation to insulin sensitivity.
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PMID:Adiponectin and leptin in relation to insulin sensitivity. 1837 Jun 42

Chronically elevated interleukin-6 (IL-6) affects lipid and lipoprotein metabolism. Individuals genetically predisposed to higher IL-6 secretion may be at risk of dyslipidemia, especially during the postprandial phase. We investigated the effect of genetic variants at the IL6 locus on postprandial lipemia in US Whites participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Subjects were given a single fat load composed of 3% of calories as protein, 14% as carbohydrate, and 83% as fat. Blood was drawn at 0 h, 3.5 h, and 6 h to determine plasma triglyceride (TG), TG-rich lipoprotein (TRL) and lipoprotein particle size. Homozygotes (GG) and heterozygotes (CG) of the -174C/G variant displayed higher plasma IL-6 concentrations compared with major allele homozygotes (CC) (P = 0.029). GG and CG subjects showed higher fasting plasma TG (P = 0.025), VLDL (P = 0.04), and large VLDL (P = 0.02) concentrations than did CC subjects. Moreover, GG and CG subjects experienced greater postprandial response of TG (P = 0.006) and TRL, including chylomicrons (P = 0.005), total VLDL (P = 0.029), and large VLDL (P = 0.017) than did CC subjects. These results suggest that the functional polymorphism -174C>G at the IL6 locus determines the difference in both fasting and postprandial TG metabolism. This phenomenon could be responsible for the observed association of this genetic variant with cardiovascular disease risk.
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PMID:The effect of IL6-174C/G polymorphism on postprandial triglyceride metabolism in the GOLDN studyboxs. 1842 May 33

Dyslipidemia, and inflammatory markers: high-sensitivity C-reactive protein (hs-CRP), myeloperoxidase (MPO), lipoprotein associated phospholipase A2(Lp-PLA2), and lipid peroxides (LP) are insufficient to predict the onset, extent, and prognosis of CHD. Lipoxins (LXs), resolvins, and protectins are derived from omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 arachidonic acid in the presence of aspirin; whereas nitrolipids are formed due to the interaction between polyunsaturated fatty acids and nitric oxide (NO). LXs, resolvins, protectins, and nitrolipids are endogenous anti-inflammatory lipid molecules that inhibit production of interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-alpha), suppress free radical generation, enhance NO generation; and accelerate tissue repair. Thus, beneficial actions of EPA/DHA and aspirin in CHD could be attributed to the formation of LXs, resolvins, protectins, and nitrolipids and suggest that their plasma levels aid in the prediction and prognosis of CHD.
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PMID:Can endogenous lipid molecules serve as predictors and prognostic markers of coronary heart disease? 1848 92

Among the adverse effects attributed to antiretroviral therapy, one of the most striking is probably the appearance of the lipodystrophy syndrome and its associated metabolic derangements, given its potential long-term effect as a cardiovascular risk factor. Since not all patients who receive antiretroviral drugs experience these adverse effects, a host genetic predisposition has been postulated. However, currently available data on this issue is inconclusive and preliminary. It has been consistently demonstrated that polymorphisms in the genes that encode for apolipoproteins A5, C3 and E, for the cholesterol ester transporter proteins (CETP), and in the ATP binding cassette type A1 (ABCA1) influence the development of dyslipidemia in patients treated with antiretroviral drugs, particularly if the therapeutic regimen includes protease inhibitors. Data on the effect of polymorphisms in the sterol regulatory ester binding protein type 1 (SREBP1) are inconsistent. The effect of mitochondrial DNA mutations on the risk of lipodystrophy has been assessed, with inconclusive data. No polymorphisms in the lamin A gene have been detected. Investigations have assessed the effect of diverse polymorphisms in the genes that encode for several proinflammatory cytokines such as tumour necrosis factor alpha (TNF-alpha), interleukin-1-beta (IL-1beta) and interleukin-6 (IL-6). The results show inconsistent data in the case of TNF-alpha, no association in the case of IL-6, and preliminary positive associations in IL-1beta. In contrast, polymorphisms in the genes encoding for stromal derived factor 1 (SDF-1) and for monocyte chemoattractant protein 1 (MCP-1) have been shown to influence the development of subclinical atherosclerosis in HIV-1-infected patients treated with antiretroviral drugs.
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PMID:[Toxicogenetics of antiretroviral treatment (1): lipodystrophy, metabolic perturbations and atherosclerosis]. 1868 Jun 92

Erythropoietin-stimulating agent (ESA) hyporesponsiveness is aggravated by chronic inflammation in maintenance hemodialysis (MHD) patients. Dyslipidemia is prevalent in MHD patients. Statin therapy has been demonstrated to not only be effective in lowering lipid levels, but also numerous pleiotropic effects including anti-inflammatory, anti-fibrotic and endothelial function improvement. Recently, a retrospective study has shown that statin therapy decreases ESA requirements in MHD patients. We conducted a prospective study to analyze the effect of statin therapy on ESA hyporesponsiveness, and especially emphasized its anti-inflammatory benefits in MHD patients. This prospective study enrolled 30 patients with baseline cholesterol >220 mg/dl. Low-dose atorvastatin (10 mg/day) was prescribed for 12 weeks. We prospectively recorded patients' biochemistry and hematological profiles, ESA prescription and some inflammatory markers at baseline, 4 weeks and 12 weeks. Statistically significant changes were noted after 4 and 12 weeks of statin therapy for cholesterol (272.5 +/- 41.1 to 184.4 +/- 37.6 and 196.4 +/- 40.2 mg/dl, p < 0.05) and ESA hyporesponsiveness, which demonstrated as erythropoietin to hematocrit ratio (EHR) (129.3 +/- 58.2 to 122.3 +/- 53.5 and 121.0 +/- 53.3 EPO U/Hct/week, p < 0.05). Mean values for proinflammatory cytokines included interleukin-6 and tumor necrotic factor-alpha levels decreased by 30.8 and 10.6%, respectively. Thus, these data suggest that statin therapy may improve ESA hyporesponsiveness in dialysis patients. This improvement in ESA hyporesponsiveness is associated with the effects of statins on inflammation.
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PMID:Atorvastatin increases erythropoietin-stimulating agent hyporesponsiveness in maintenance hemodialysis patients: role of anti-inflammation effects. 1897 40

Atherosclerosis and osteoporosis share many risk factors, but their independent association is unclear. The authors investigated the independent associations between volumetric trabecular bone mineral density (vBMD) of the lumbar spine and coronary artery calcium (CAC) and abdominal aortic calcium (AAC). During 2002-2005, they used quantitative computed tomography to assess vBMD and the presence and extent of CAC and AAC among 946 women (mean age = 65.5 years) and 963 men (mean age = 64.1 years) in a substudy of the Multi-Ethnic Study of Atherosclerosis. Prevalences of CAC were 47% and 68% in women and men, respectively, and AAC prevalences were 70% and 73%. Sequential, sex-specific regression models included adjustment for age, ethnicity, body mass index, hypertension, dyslipidemia, diabetes mellitus, smoking, alcohol consumption, physical activity, interleukin-6, C-reactive protein, homocysteine, and sex hormones. After full adjustment, lower vBMD was associated with greater CAC score among women (P < 0.002) and greater AAC score among women (P = 0.004) and men (P < 0.001). After adjustment, vBMD quartile was inversely associated with CAC prevalence (P-trend = 0.05) in women and AAC prevalence (P-trend < 0.01) in men. Partially and fully adjusted models showed similar results. Though modest, these significant, independent associations suggest that atherosclerosis and bone loss may be related.
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PMID:Association of coronary artery and aortic calcium with lumbar bone density: the MESA Abdominal Aortic Calcium Study. 1906 43


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