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)

Assessment of body fat distribution, particularly visceral adipose tissue, may be important for accurate risk evaluation for cardiovascular disease in the elderly. This 1997-1998 US study examined the association of incident myocardial infarction (MI) with total adiposity (body mass index and fat mass) and body fat distribution (waist-to-thigh ratio, waist circumference, visceral and subcutaneous adipose tissue) in well-functioning men (n = 1,116) and women (n = 1,387) aged 70-79 years enrolled in the Health, Aging and Body Composition Study. There were 116 MI events (71 in men, 45 in women) during an average follow-up time of 4.6 (standard deviation, 0.9) years. No association was found between incident MI and the adiposity or fat distribution variables for men. For women, visceral adipose tissue was an independent predictor of MI (hazard ratio = 1.67, 95% confidence interval: 1.28, 2.17 per standard-deviation increase; p < 0.001). No association was found between body mass index or total fat mass and MI events in women. The association of visceral adipose tissue with MI in women was independent of high density lipoprotein cholesterol, interleukin-6 concentration, hypertension, and diabetes (hazard ratio = 1.79, 95% confidence interval: 1.24, 2.58 per standard-deviation increase; p < 0.01). The amount of adipose tissue stored in the intraabdominal cavity is an important, independent risk factor for MI in well-functioning, elderly women.
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PMID:Association of visceral adipose tissue with incident myocardial infarction in older men and women: the Health, Aging and Body Composition Study. 1546 96

Diabetics have a much greater morbidity and mortality due to cardiovascular disease (CVD) than nondiabetics. Furthermore, diabetic women have a 3.8-fold greater risk for CVD compared to diabetic men. Inflammation is now considered a risk factor for CVD and it has been demonstrated that inflammation also plays a role in diabetes. One component of inflammation that has reported to be increased in patients with diabetes only and CVD only are proinflammatory cytokines, particularly interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), and interleukin-1 (IL-1beta). This study was performed to test the hypothesis that these proinflammatory cytokines were increased in women with CVD and further increased in diabetic women with CVD compared to nondiabetic women with CVD and healthy age-matched controls. We found that IL-6 was increased in diabetic women with CVD compared to healthy age-matched controls (1.41 = 0.48 to 0.33 +/- 0.06 pg/ml, P < .05). IL-6 was also increased in diabetic women without CVD compared to healthy age-matched controls, but not significantly (0.96 +/- 0.27 to 0.33 +/- 0.06 pg/ml). We found that TNF-alpha was increased in diabetic women with and without CVD compared to healthy age-matched controls, but not significantly (4.53 +/- 1.38 to 3.93 +/ -0.53 to 2.33 +/- 0.89 pg/ml). IL-1beta was not significantly different among any of the four groups of women. These results indicate that both IL-6 and TNF-alpha are chronically increased in diabetic women with and without CVD compared to nondiabetic women. The additive concentration of cytokines in diabetes and CVD suggests a common inflammatory state in both diabetes and CVD.
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PMID:Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease. 1553 Nov 84

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this population, inflammation (a common phenomenon in ESRD), and other non-traditional risk factors are likely to contribute. Among several inflammatory biomarkers used to assess inflammation, high-sensitivity C-reactive protein (hs-CRP) has attracted the most interest. Indeed, in the general population the consistency of prognostic data for hs-CRP and the practicality of its use have led to suggestions that CRP should be used as a clinical criterion for global cardiovascular risk prediction. As CRP is so strongly associated with vascular disease, it has been suggested that this protein is not only a marker, but also a mediator, of atherogenesis. Indeed, recent in vitro data from studies on endothelial cells, monocytes-macrophages and smooth muscle cells support a direct role for CRP in atherogenesis. In ESRD, hs-CRP has been proven to be a strong predictor of both cardiovascular and all-cause mortality, and associated with oxidative stress, vascular calcification and endothelial dysfunction. As recent studies suggest that interleukin-6 may be a somewhat better outcome predictor than hs-CRP, comparative studies are needed to evaluate which inflammation biomarker is the most cost-effective predictor of outcome in the ESRD patient population.
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PMID:C-reactive protein in end-stage renal disease: are there reasons to measure it? 1562 40

Trans fatty acid intake has been associated with a higher risk of cardiovascular disease. The relation is explained only partially by the adverse effect of these fatty acids on the lipid profile. We examined whether trans fatty acid intake could also affect biomarkers of inflammation and endothelial dysfunction including C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR-2), E-selectin, and soluble cell adhesion molecules (sICAM-1 and sVCAM-1). We conducted a cross-sectional study of 730 women from the Nurses' Health Study I cohort, aged 43-69 y, free of cardiovascular disease, cancer, and diabetes at time of blood draw (1989-1990). Dietary intake was assessed by a validated FFQ in 1986 and 1990. CRP levels were 73% higher among those in the highest quintile of trans fat intake, compared with the lowest quintile. IL-6 levels were 17% higher, sTNFR-2 5%, E-selectin 20%, sICAM-1 10%, and sVCAM-1 levels 10% higher. Trans fatty acid intake was positively related to plasma concentration of CRP (P = 0.009), sTNFR-2 (P = 0.002), E-selectin (P = 0.003), sICAM-1 (P = 0.007), and sVCAM-1 (P = 0.001) in linear regression models after controlling for age, BMI, physical activity, smoking status, alcohol consumption, intake of monounsaturated, polyunsaturated, and saturated fatty acids, and postmenopausal hormone therapy. In conclusion, this study suggests that higher intake of trans fatty acids could adversely affect endothelial function, which might partially explain why the positive relation between trans fat and cardiovascular risk is greater than one would predict based solely on its adverse effects on lipids.
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PMID:Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. 1573 94

An elevated plasma fibrinogen level is an independent risk factor for cardiovascular disease. Therefore, an understanding of the regulation of fibrinogen expression is important. Inflammation and genetic variation of the fibrinogen beta gene regulate plasma fibrinogen levels, and there are indications that inflammation and genetic variation interact. The aim of our study was to gain more understanding of the regulation of the inflammatory response of the fibrinogen beta gene and to determine the effects of genetic variation. Luciferase reporter gene assays in hepatoma cells, mutation analysis, and electrophoretic mobility shift assays were used to investigate the transcriptional regulation of the fibrinogen beta promoter. We identified a hepatocyte nuclear factor-3 (HNF-3) site located just upstream of previously identified interleukin-6 (IL6)-responsive sequences. This HNF-3 site is essential for a full response of the promoter to IL6, which is a new function for HNF-3. The activity of the CCAAT box/enhancer-binding protein site (located 18 nucleotides downstream of the HNF-3 site and important to the IL6 response) depends on the integrity of the HNF-3 site and vice versa, explaining the necessity of HNF-3 in the IL6 response of the fibrinogen beta promoter. Furthermore, small interfering RNA to HNF-3 reduces the fibrinogen beta mRNA levels. The rare T allele of the -148C/T polymorphism, which is present between the binding sites of HNF-3 and CCAAT box/enhancer-binding protein, interferes with this mechanism, and this polymorphism is in our assay system the only genetic determinant of IL6-induced promoter activity among six polymorphisms in the fibrinogen beta promoter.
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PMID:A hepatocyte nuclear factor-3 site in the fibrinogen beta promoter is important for interleukin 6-induced expression, and its activity is influenced by the adjacent -148C/T polymorphism. 1573 87

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the western world. Its incidence has been increasing lately in the developing countries. Much evidence suggests a major role for inflammation in all phases of atherosclerosis. Cell adhesion molecules, cytokines, chemokines, and monocytes-macrophages as well as T lymphocytes play a pivotal role in atherogenesis. C-reactive protein (CRP), a downstream marker of inflammation, in addition to being a risk marker for CVD, could contribute to atherosclerosis. Dietary micronutrients with anti-inflammatory properties, specially alpha-tocopherol, may play an important role with regard to the prevention and treatment of CVD. alpha-Tocopherol has been shown to have anti-inflammatory effects both in vitro and in vivo. alpha-Tocopherol therapy, especially at high doses, has been shown to decrease release of pro-inflammatory cytokines (such as interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) and the chemokine interleukin-8, and to decrease adhesion of monocytes to endothelium. In addition, alpha-tocopherol has been shown to decrease CRP levels in patients with CVD and having related risk factors for CVD (such as diabetes and smoking). Furthermore, pro-inflammatory cytokines and plasminogen activator inhibitor-1 (PAI-1) levels have also been shown to be decreased with alpha-tocopherol supplementation in vivo. In this review, our focus will be on anti-inflammatory effects of alpha-tocopherol reported in in vivo studies.
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PMID:Anti-inflammatory effects of alpha-tocopherol. 1575 45

Little is known regarding cardiovascular disease risk indices in HIV-infected women. This study investigated cardiovascular disease risk indices in 100 consecutively recruited HIV-infected women and 75 healthy female control subjects. Subjects were recruited from hospital- and community-based health care providers. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, lipid, and glucose levels were the main outcome measures. CT scan, dual-energy x-ray absorptiometry (DXA), and anthropometry were used to assess body composition. Although similar in age, weight, and racial composition, HIV-infected women demonstrated higher CRP (4.6 +/- 0.7 vs. 2.3 +/- 0.4 mg/L, P = 0.007), IL-6 (2.7 +/- 0.2 vs. 1.8 +/- 0.1 pg/mL, P = 0.02), triglyceride (1.84 +/- 0.21 vs. 0.85 +/- 0.05 mM, P = 0.0002), 2-hour glucose after oral glucose challenge (6.88 +/- 0.22 vs. 5.72 +/- 0.17 mM, P = 0.0003), and fasting insulin (81 +/- 8 vs. 45 +/- 2 pM, P = 0.0002) and lower high-density lipoprotein cholesterol (1.17 +/- 0.03 vs. 1.45 +/- 0.05 mM, P < 0.0001) and adiponectin (5.4 +/- 0.3 vs. 7.6 +/- 0.5 mg/L, P = 0.0001) levels compared with the control population. HIV-infected women had more abdominal visceral fat and less extremity fat by CT and DXA scan and demonstrated a higher waist-to-hip ratio (WHR) than the control population. Within the HIV group, CRP and other indices were significantly related to body composition in stepwise regression models. Among all subjects, WHR, but not HIV status, was significantly related to CRP and other cardiovascular disease risk indices. HIV-infected women demonstrate significantly increased risk factors for cardiovascular disease in association with abnormal fat distribution.
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PMID:Increased cardiovascular disease risk indices in HIV-infected women. 1585 13

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.
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PMID:Lifestyle modification and endothelial function in obese subjects. 1585 97

Being overweight or obese has become highly prevalent in Western countries and are rapidly reaching epidemic proportions in the developing world. Obesity-related disorders, such as hypertension and diabetes, are also increasing at an alarming rate. The relationship between obesity, hypertension and insulin resistance is well recognised, but the molecular mechanisms involved remain relatively poorly understood. Adipose tissue plays a key role in the pathogenesis of the metabolic syndrome. It serves as an important source of pro-inflammatory molecules, including leptin, tumour necrosis factor alpha, angiotensin II and interleukin-6, as well as anti-inflammatory molecules, such as adiponectin. Knowledge of how these adipose tissue-derived factors influence metabolic and cardiovascular disease has recently expanded. Leptin is now considered to play a key role in the elevation of sympathetic activity commonly found in obese, hypertensive patients, and decreased secretion of adiponectin appears to be an important predictor of diabetes. The ectopic storage of excess fat in skeletal muscle, liver or pancreas, due to the decreased capacity of adipose tissue to scavenge excess calories, may also play a role in the development of insulin resistance and type 2 diabetes. Overall, continuing research into the relationship between adipose-tissue biology and metabolic abnormalities may lead to a better understanding of the molecular mechanisms underlying the relationship between obesity and cardiovascular disease, and ultimately provide alternative treatments for the control of potentially life-threatening conditions.
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PMID:Obesity, hypertension and insulin resistance. 1586 17

Obstructive sleep apnea (OSA) is a prevalent disorder particularly among middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness.' In 1997, we first reported that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNFalpha plasma levels and the body-mass-index (BMI). In subsequent studies, we showed that IL-6, TNFalpha, and insulin levels were elevated in sleep apnea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnea. Furthermore, our findings that women with the polycystic ovary syndrome (PCOS) (a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness, suggests a pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnea and sleepiness in obese patients may be manifestations of the Metabolic Syndrome, include: obesity without sleep apnea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity, and age; increased prevalence of sleep apnea in post-menopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA; lack of effect of continuous positive airway pressure (CPAP) in obese patients with apnea on hypercytokinemia and insulin resistance indices; and that the prevalence of the metabolic syndrome in the US population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic sleep apnea in general random samples. Finally, the beneficial effect of a cytokine antagonist on EDS in obese, male apneics and that of exercise on SDB in a general random sample, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnea in humans. In conclusion, accumulating evidence provides support to our model of the bi-directional, feed forward, pernicious association between sleep apnea, sleepiness, inflammation, and insulin resistance, all promoting atherosclerosis and cardiovascular disease.
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PMID:Sleep apnea is a manifestation of the metabolic syndrome. 1589 51


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