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)

An increasing number of researchers of the metabolic syndrome assume that many mechanisms are involved in its complex pathophysiology such as an increased sympathetic activity, disorders of the hypothalamo-pituitary-adrenal axis, the action of chronic subclinical infections, proinflammatory cytokines, and the effect of adipocytokines or psychoemotional stress. An increasing body of scientific research in this field confirms the role of the neurotrophins and mastocytes in the pathogenesis of inflammatory and immune diseases. Recently it has been proved that neurotrophins and mastocytes have metabotrophic effects and take part in the carbohydrate and lipid metabolism. In the early stage of the metabolic syndrome we established a statistically significant increase in the plasma levels of the nerve growth factor. In the generalized stage the plasma levels of the neutrophines were statistically decreased in comparison to those in the healthy controls. We consider that the neurotrophin deficit is likely to play a significant pathogenic role in the development of the metabolic anthropometric and vascular manifestations of the generalized stage of MetSyn. We suggest a hypothesis for the etiopathogenesis of the metabolic syndrome based on the neuro-immuno-endocrine interactions. The specific pathogenic pathways of MetSyn development include: (1) increased tissue and plasma levels of proinflammatory cytokines Interleukin-1(IL-1), Interleukin-6 (IL-6 ) and tumor necrosis factor - alpha (TNF-alpha) caused by inflammatory and/or emotional distress; (2) increased plasma levels of neurotrophin - nerve growth factor (NGF) caused by the high IL-1, IL-6 and TNFalpha levels; (3) high plasma levels of NGF which enhance activation of: the autonomous nerve system--vegetodystonia (disbalance of neurotransmitters); Neuropeptide Y (NPY)--enhanced feeding, obesity and increased leptin plasma levels; hypothalamo-pituitary-adrenal axis--increased corticotropin-releasing hormone (CRH) and cortisol (hormonal disbalance); immune cells--increased number and degranulation of mastocytes (MC)--immunological disbalance; (4) as a result of 1-3 insulin resistance is exhibited leading to diabetes mellitus. The hypothesis is confirmed by results obtained after 6-month nonsteroid anti-inflammatory treatment of patients with MetSyn. These results are reported in a separate publication.
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PMID:Metabolic syndrome--neurotrophic hypothesis. 1654 15

There are few data concerning the relationship between diabetes mellitus, the metabolic syndrome and inflammation following elective percutaneous coronary intervention (PCI). The purpose of this study was to assess basal and peak levels of candidate cytokines in 40 patients undergoing elective PCI. Patients were categorised as having diabetes mellitus, the metabolic syndrome, or neither. Patients with the metabolic syndrome exhibited significantly greater levels of tumour necrosis factor-alpha over the study period, although this was unrelated to PCI. There was a trend for increased levels of interleukin-6 following PCI, primarily among patients with metabolic syndrome. Basal levels of monocyte chemoattractant protein-1 (MCP-1) were not different among study groups; however, the metabolic syndrome cohort had a trend towards increased circulating levels of MCP-1 after PCI. In this patient population, the metabolic syndrome correlates with a heightened inflammatory response following elective PCI.
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PMID:Metabolic syndrome-mediated inflammation following elective percutaneous coronary intervention. 1630 70

Prostate cancer, the third most common cancer in men worldwide, varies substantially according to geographic region and race/ethnicity. Obesity and associated endocrine variation are foremost among the risk factors that may underlie these regional and ethnic differences. The association between obesity and prostate cancer incidence is complex and has yielded inconsistent results. Studies that have linked obesity with prostate cancer mortality, advanced stage disease, and higher grade Gleason score, however, have produced more consistent findings, indicating that obesity may not necessarily increase the risk of prostate cancer, but may promote it once established. Additionally, metabolic syndrome, which includes disturbed glucose metabolism and insulin bioactivity, may also be associated with prostate carcinogenesis. Adipokines, defined as biologically active polypeptides produced by adipose tissue, have been linked with a number of carcinogenic mechanisms, including angiogenesis, cell proliferation, metastasis, and alterations in sex-steroid hormone levels. A number of emerging studies have implicated the role of adipokines in prostate carcinogenesis. This review explores the specific roles of several adipokines as putative mediating factors between obesity and prostate cancer with particular attention to leptin, interleukin-6 (IL-6), heparin-binding epidermal growth factor-like growth factor (HB-EGF), vascular endothelial growth factor (VEGF) and adiponectin.
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PMID:Obesity, adipokines, and prostate cancer (review). 1646 80

Polycystic ovary syndrome (PCOS) is a diagnosis made between late adolescence and the menopause in 5-10% of women. PCOS is a heterogeneous disorder of unknown etiology characterized by hyperandrogenic chronic anovulation. This syndrome consists of a diverse constellation of signs and symptoms, such as hirsutism, acne, acanthosis nigricans, obesity, menstrual irregularities, anovulation, and/or infertility. Features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia, are common in this patient population. Recent insights into the pathophysiology of PCOS have shown insulin resistance and hyperinsulinemia to play a substantial role. Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Recent studies show that serum levels of inflammatory mediators, such as tumor necrosis factor-alpha and interleukin-6, are increased in the insulin-resistant conditions of obesity and PCOS. The optimal modality for long-term treatment should have positive effects on androgen synthesis, sex hormone-binding globulin production, the lipid profile, insulin sensitivity, inflammatory mediators, and clinical symptoms including acne, hirsutism, and irregular menstrual cycles. Treatment with insulin-sensitizing agents is a relatively new therapeutic strategy in women with PCOS. Current research has shown that the use of diabetes mellitus management practices aimed at reducing insulin resistance and hyperinsulinemia (such as weight reduction and the administration of oral antidiabetic drugs) can not only reverse testosterone and luteinizing hormone abnormalities and restore menstrual cycles, but can also improve glucose, insulin, proinflammatory cytokine, and lipid profiles.Clinical treatment with troglitazone, a member of the thiazolidinedione family, for the management of PCOS complications such as insulin resistance, hyperandrogenism, and anovulation was found to have beneficial effects; however, it was taken off the market over concerns of hepatotoxicity. Although troglitazone is no longer available in the US, numerous clinical trials have established the role of thiazolidinediones in the treatment of women with PCOS. Clinical data emerging regarding the utility of two of the newer, safer thiazolidinediones, pioglitazone and rosiglitazone, for this patient population, consistently demonstrate effective improvements of endocrine and ovulatory performance in women with PCOS. The benefit and importance of lifestyle modification and weight reduction, when it can be achieved, is still an important component in the long-term treatment of PCOS. Pharmacologic reduction in insulin levels using thiazolidinediones appears to offer another therapeutic modality for PCOS, which may ameliorate the progress of both hyperinsulinemia and hyperandrogenism. However, additional studies of patients so treated are necessary before these agents can be considered first-line treatment for PCOS. Convincing data from randomized controlled trials with sufficient power to detect both the benefits and risks of long-term treatment with thiazolidinediones in women with PCOS remain to be obtained.
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PMID:Thiazolidinediones for the therapeutic management of polycystic ovary syndrome : impact on metabolic and reproductive abnormalities. 1667 59

Large interventional studies have shown that statins may reduce the incidence of type 2 diabetes mellitus. However, it is uncertain whether short-term statin therapy can affect insulin sensitivity in patients with the metabolic syndrome. We evaluated the effect of atorvastatin (10 mg/day) in 10 insulin-resistant subjects (age 40 +/- 12 years, body mass index 33.6 +/- 5.2 kg/m(2), triglycerides 2.84 +/- 1.99 mmol/L [249 +/- 175 mg/dl], glucose 6.06 +/- 0.67 mmol/L [109 +/- 12 mg/dl)] using the homeostasis model assessment (HOMA) index (parameter of insulin resistance derived from fasting glucose and fasting insulin concentrations; 5.7 +/- 2.6) in a randomized placebo-controlled, double-blind, crossover study. Subjects were randomized to receive placebo or atorvastatin, each given for 6 weeks separated by a 6-week wash-out period. At the beginning and end of each treatment phase, the patients underwent an oral glucose tolerance test, a 72-hour continuous glucose measurement, and a detailed lipid determination, including a standardized fat tolerance test. Compared with placebo, atorvastatin resulted in a significant (p = 0.05) reduction in the HOMA index (-21%), fasting C-peptides (-18%), glucose (area under the curve during the oral glucose tolerance test, -7%), and a borderline (p = 0.08) reduction of insulin (-18%). The parameters derived from the continuous 72-hour glucose monitoring did not change. A significant reduction also occurred in the total and low-density lipoprotein cholesterol concentrations, although the fasting and postprandial triglyceride concentrations did not change significantly. However, we found a significant correlation between atorvastatin-induced changes in the HOMA and baseline HOMA and between the atorvastatin-induced changes in triglycerides and insulin concentrations. The free-fatty acid, interleukin-6, and high sensitivity C-reactive protein concentrations did not change. Our data indicated that in insulin-resistant, nondiabetic subjects, 6 weeks of atorvastatin (10 mg/day) resulted in significant improvement in insulin sensitivity.
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PMID:Effect of atorvastatin (10 mg/day) on glucose metabolism in patients with the metabolic syndrome. 1678 23

Interleukin-6 (IL-6) is a pleiotropic cytokine which has been proposed as "cytokine for gerontologists" and linked to age-related metabolic disturbances such as the metabolic syndrome or type 2 diabetes. Polymorphisms located in the promoter region of IL-6 have been reported to be involved in the regulation of IL-6 transcription. This study investigates whether IL-6 promoter variants -174 G/C and -573 G/C are associated with quantitative traits related to the metabolic syndrome (International Diabetes Federation criteria) in a population of normoglycemic subjects (n=878) from the latest KORA survey (KORA S4). Genotyping was performed using MALDI-TOF MS. Besides lower height (p=0.01) the -174 CC genotype was independently associated with lower waist (p=0.002) and hip (p=0.01) circumferences in men. Furthermore, the -174 CC genotype was associated with BMI (p=0.004) when adjusted for waist and hip circumference. The present study does not suggest associations with further components of the metabolic syndrome. The association with height seems to be the central factor indicating an influence of IL-6 on growth through impaired bone metabolism. However, the complex relationships need further investigation.
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PMID:IL-6 promoter polymorphisms and quantitative traits related to the metabolic syndrome in KORA S4. 1679 5

We examined the association between interleukin-10 (IL-10), adiponectin levels and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP). Furthermore, the association of these anti-/pro-inflammatory cytokine levels with the metabolic syndrome was investigated. The study subjects were composed of 312 Korean individuals without diabetes. Serum adiponectin level was associated with hsCRP (r=-0.21, P<0.001), IL-6 (r=-0.13, P<0.05) and IL-10 (r=-0.22, P<0.001) levels. Subjects without the metabolic syndrome showed higher adiponectin (17.03 microg/ml versus 13.85 microg/ml, P<0.001) and IL-10 (4.74 pg/ml versus 4.34 pg/ml, P=0.014) levels, and lower serum hsCRP (0.38 microg/ml versus 0.66 microg/ml, P=0.001) and IL-6 (0.94 pg/ml versus 1.32 pg/ml, P=0.009) levels compared to those with the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome was associated with sex, age, waist circumference, systolic blood pressure, HDL cholesterol, triglyceride, fasting blood glucose and interleukin-10. Furthermore, serum adiponectin levels are associated with serum hsCRP, IL-6 and IL-10 levels. These results suggest that adiponectin might be associated with the metabolic syndrome through regulation of pro-/anti-inflammatory cytokines.
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PMID:Serum adiponectin, interleukin-10 levels and inflammatory markers in the metabolic syndrome. 1687 12

It is known that overweight induces fibrinolysis impairment. Since this association has not been completely explored in patients with venous thromboembolism (VTE), we aimed to investigate its presence in young women with VTE and, if present, to determine its extent and the factors that influence it. Thirty women aged 23-49 years in the stable period after VTE were included [19 overweight (body mass index > or = 25) and 11 normal weight]; 52 healthy women (27 overweight and 25 normal weight) served as controls. The euglobulin clot lysis time (ECLT), plasminogen, D-dimer, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen and activity, lipids, fasting plasma glucose, insulin, fibrinogen, interleukin-6 and sedimentation rate were compared between the groups. Overweight patients had more impaired fibrinolysis (delayed ECLT, higher PAI-1 and t-PA antigen) than overweight controls (and normal weight patients). There was no difference in levels of insulin, glucose, fibrinogen and interleukin-6, whereas the sedimentation rate was significantly elevated in overweight patients compared with overweight controls [16 (8-31) versus 8 (5-12), P < 0.05]. The sedimentation rate in overweight patients significantly correlated with body mass index, ECLT, t-PA and PAI-1 antigen, but not with fibrinogen or interleukin-6. We found that overweight VTE patients have more prominent fibrinolysis impairment than predictable from parameters of metabolic syndrome and that is associated with an elevated sedimentation rate. This association could represent a new thrombotic risk profile in overweight women.
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PMID:A metabolic syndrome independent association between overweight, fibrinolysis impairment and low-grade inflammation in young women with venous thromboembolism. 1698 50

The mechanisms by which thiazolidinediones exert beneficial effects on the endothelium are still not clear. We examined the effects of rosiglitazone on the plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and lipid profiles), markers of inflammation (high-sensitivity C-reactive protein [CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between changes in endothelium-dependent flow-mediated dilation of the brachial artery and changes in these markers to elucidate their roles in mediating the vascular protective effects of rosiglitazone. Of 70 nondiabetic patients who met a modified National Cholesterol Education Program definition of the metabolic syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to receive placebo for 8 weeks. At study end, treatment with rosiglitazone had significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p <0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (-16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and diastolic blood pressures. Rosiglitazone treatment significantly improved flow-mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001) of the right brachial artery. On multivariate analysis, changes in ADMA, endothelin-1, and CRP were independent predictors of improved endothelial reactivity with rosiglitazone. In conclusion, we have, for the first time, demonstrated the independent associations between the improvement in flow-mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of treatment with rosiglitazone in nondiabetic patients with the metabolic syndrome. These findings suggest that decreases in ADMA, endothelin-1, and CRP may serve as possible mechanisms for the improvement in endothelial function conferred by rosiglitazone treatment.
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PMID:Relation of improvement in endothelium-dependent flow-mediated vasodilation after rosiglitazone to changes in asymmetric dimethylarginine, endothelin-1, and C-reactive protein in nondiabetic patients with the metabolic syndrome. 1702 71

Elevated plasma interleukin-6 (IL-6) is associated with coronary heart disease (CHD), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM). We and others have described an association between the human interleukin-6 -174G>C gene variant and body mass index (BMI). Within our previous sample of subjects with T2DM, we measured plasma IL-6 and grouped subjects by the WHO-defined metabolic syndrome, in order to study the association between the -174G>C gene variant, plasma IL-6 and the metabolic syndrome (and component parts). Genotype was obtained in 571 Caucasian subjects with plasma IL-6 measures. There was a significant association between genotype and plasma IL-6 (GG vs GC vs CC: 3.23+/-0.93 pg/ml vs 3.42+/-0.95 pg/ml vs 4.16+/-1.18 pg/ml, p=0.02; for GG/GC vs CC p=0.008). No interactions were observed between genotype and the individual components of the metabolic syndrome in determining plasma IL-6. Increased plasma IL-6 was also associated with the number of components (none vs 1 vs 2 vs > or =3: 2.67+/-0.71 pg/ml vs 2.97+/-0.94 pg/ml vs 4.07+/-1.13 pg/ml, p<0.0001). Within the sample, 76% of CC compared to 56% of GG subjects had the metabolic syndrome (p=0.007). Further analysis of association between the genotype and the components of the metabolic syndrome revealed no further associations than that with BMI previously described. The association of this gene variant with the metabolic syndrome is intimately linked with obesity per se. Further prospective work is required to explore the effect of this gene variant in relation to obesity, the metabolic syndrome and 'prediabetes'.
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PMID:Association between plasma IL-6, the IL6 -174G>C gene variant and the metabolic syndrome in type 2 diabetes mellitus. 1712 52


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