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)

Obesity is associated with increased incidence of cardiovascular mortality. However, the mechanisms that link increased fat mass with hypercholesterolemia, hypertension, endothelial dysfunction and coronary heart disease have not been fully elucidated. Unravelling the diverse neuroendocrine systems, which regulate energy balance and body fat has been a long-standing challenge in biology, with obesity as an increasingly important public health focus. Until recently, the adipocyte has been considered only a passive tissue for the storage of excess energy in the form of fat. However, there is now compelling evidence that adipocytes act as endocrine, secretory cells. It has been shown that several hormones, growth factors and cytokines are actually expressed in white adipose tissue. In a dynamic view of the adipocyte a wide range of signals emanates from white adipose tissue such as tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their respective soluble receptors. White adipose tissue also secretes important regulators of lipoprotein metabolism like lipoprotein lipase (LPL), apolipoprotein E (apoE) and cholesteryl ester transfer protein (CETP). The increasing number of products secreted by adipocytes also includes leptin, estrogen, angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), tissue factor and transforming growth factor-beta (TGF-beta). Nitric oxide synthase (NOS) has been also reported to be expressed in white adipose tissue. Acylation stimulating protein (ASP), adipophilin, adipoQ, adipsin, monobutyrin, agouti protein and factors related to pro-inflammatory and immune processes have also been shown to be released by white adipocytes. Since blood vessels express receptors for most of the adipocyte-derived factors, adipose tissue seems to play a key role in cardiovascular physiology through the existence of a network of local and systemic signals. The current knowledge in this field will be reviewed in the broader perspective of cardiovascular physiology and pathophysiology.
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PMID:The adipose tissue as a source of vasoactive factors. 1532 Jul 86

The adipose tissue produces a vast number of molecules called adipokines such as leptin, tumoral necrosis factor (TNFalpha), interleukins and adiponectin. Many of the metabolic disturbances associated with obesity and the metabolic syndrome may be due to citokine production by adipocytes. The adipose tissue increases the soluble fractions of TNFalpha leading to a rise in its biological activity. The activation of TNFalpha system causes insulin resistance through different mechanisms such as defects in receptor fosforilation and reduction in insulin-sensitive glucose transporters. TNFalpha is also involved in the pathophysiology of hypertension and dyslipidaemia associated with obesity and insulin resistance. More than one third of interleukin-6 (IL-6) concentrations come from the adipocytes. It has been demonstrated a role for IL-6 in the development of hyperlipidemia, diabetes and hypertension. In contrast to the rest of adipokines, adiponectin is reduced in obesity, diabetes or cardiovascular disease. Adiponectin improves insulin resistance, dyslipidaemia and adhesion to endothelial cells protecting from atherosclerosis development. Thus, adipokines have an important role in the pathophysiology of metabolic syndrome by different mechanisms involving metabolic and vascular effects.
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PMID:[Obesity and inflammation]. 1538 13

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

Heart failure (HF) is a complex clinical syndrome due to ischaemic heart disease, idiopathic cardiomyopathy, hypertension, valve heart disease and others. It is not clear if the etiology of HF influences decreased in this syndrome exercise tolerance. Controversial is also dependence of cytokine levels on etiology of HF. The aim of the study was to compare exercise capacity and cytokines levels in pts with ischaemic and dilated cardiomyopathy. We analyzed circulating levels of TNF-alpha and its soluble receptors sTNF-RI and sTNF-RII, and interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in 41 pts with CHF, functional class NYHA I-IV, mean EF--25.2 +/- 7.1%. For determination of cytokines level (using R & D System tests) venous blood was withdrawn after 30 minutes of supine rest. All underwent echocardiography and cardiopulmonary exercise stress testing. Dilated cardiomyopathy (DCM) was diagnosed in 21 pts, ischaemic (ICM) in 20 pts. Pts with DCM were younger then with ICM (48 +/- 6.6 vs 56 +/- 6.6 yrs; p = 0.001). There were no significant differences between groups concerning BMI and EF. There were no significant differences in the level of TNF-alpha and sTNF-RI between groups. There was a trend of increased sTNF-RII in pts with ICM (3179.7 +/- 832.7 vs 2699 +/- 680.1 pg/ml; p = 0,07), IL-1beta (2.55 +/- 2.41 vs 1.49 +/- 1.68 pg/ml; p = 0.087) and IL-6 (6.25 +/- 2.21 vs 4.98 +/- 3.64 pg/ml; p = 0.065), and significant increased ESR (11.2 +/- 9.5 vs 5.5 +/- 4.7 mm/h; p = 0.04). Peak VO2 was reduced in pts with ICM group as compared to those with DCM (14.1 +/- 3.7 vs 18.1 +/- 4.8 ml/kg/min; p = 0.0069). In chronic heart failure circulating levels of cytokines tended to be higher in pts with ischaemic origin of the syndrome. The exercise capacity is lower in ischaemic cardiomyopathy.
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PMID:[Cardiopulmonary exercise testing and cytokines in chronic heart failure. Comparison of patients with ischaemic and with dilated cardiomyopathy]. 1550 92

The leukocyte-type 12/15-lipoxygenase (12/15-LO) has been implicated in the pathogenesis of atherosclerosis, hypertension, and diabetes. 12/15-LO and its products are associated with LDL oxidation, cellular growth, migration, adhesion, and inflammatory gene expression in monocytes/macrophages, endothelial cells, and vascular smooth muscle cells (VSMCs). Our objective, therefore, was to develop novel expression vectors for short interfering RNAs (siRNAs) targeting 12/15-LO to evaluate its functional relevance in macrophages and VSMCs. We used a PCR-based approach to rapidly identify effective siRNA target sites on mouse 12/15-LO and initially tested their efficacy on a fusion construct of 12/15-LO cDNA and enhanced green fluorescent protein. We then cloned these U6 promoter+siRNA PCR products into plasmid vectors [short hairpin siRNAs (shRNAs)] to knockdown endogenous 12/15-LO expression in mouse macrophages and also rat and mouse VSMCs. Furthermore, the functional effects of shRNA-mediated 12/15-LO knockdown were noted by the reduced oxidant stress and chemokine [monocyte chemoattractant protein-1 (MCP-1)] expression in a differentiated mouse monocytic cell line as well as by the reduced cellular adhesion and fibronectin expression in VMSCs. Knocking down 12/15-LO expression also reduced the expression of inflammatory genes, MCP-1, vascular cell adhesion molecule-1, and interleukin-6 in VSMCs. Our results illustrate the functional relevance of 12/15-LO activation in macrophages and VSMCs and its relationship to oxidant stress and inflammation.
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PMID:Effects of silencing leukocyte-type 12/15-lipoxygenase using short interfering RNAs. 1557 42

Obstructive sleep apnea syndrome (OSAS) is usually associated with conditions known to increase insulin resistance and cardiovascular risk, such as hypertension, obesity, and diabetes. Thus, investigating whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure treatment (CPAP) might improve insulin sensitivity brings up considerable methodological problems. Even if insulin sensitivity improves, it is hard to distinguish between an effect of CPAP treatment, e.g. in the reduction of nocturnal sympathetic activity caused by the sleep disturbance, and concomitant factors, such as weight loss. Two recent investigations were able to prove that OSAS is an independent risk factor for insulin resistance: one study in a statistical approach, the other by demonstrating a significant improvement of insulin sensitivity already two days after onset of CPAP therapy, thus clearly ruling out such confounding factors as changes in lifestyle or weight loss. However, it is still not clear if this improvement in insulin sensitivity is accompanied by an improvement in the usually elevated cardiovascular risk of patients with OSAS. Since a decrease in elevated markers of subclinical inflammation--nowadays regarded as the main culprit of cardiovascular complications and atherosclerosis--such as Interleukin-6 and C-reactive protein has been reported during CPAP therapy, and since an improvement in left ventricular function and a decrease in blood pressure were also reported under CPAP treatment, there are several good reasons to assume an improvement in metabolical function in OSAS patients due to CPAP treatment.
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PMID:Insulin resistance and other metabolic aspects of the obstructive sleep apnea syndrome. 1573 78

Interleukin-6 (IL-6), the major proinflammatory cytokine, has been described to be associated with the hypertensive and atherosclerotic states. We aimed to explore whether the concentration of circulating IL-6 and adhesion molecules could be modified by decreasing blood pressure in hypertensive subjects. A total of 30 subjects (18 men), aged 34-48 years, were enrolled in this study, 17 hypertensive never-treated patients (HTA) and 13 normotensive subjects (C). HTA subjects were treated with irbesartan, 150-300 mg/day for 3 months, and serum IL-6, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, sP-selectin, sE-selectin and monocyte chemoattractant protein-1 were measured at 0 and 12 weeks. The two study groups were similar in age, body mass index (BMI) and gender. At baseline, circulating IL-6 levels, but not adhesion molecules, were significantly associated with systolic blood pressure (r=0.41; P=0.03) and BMI (r=0.53; P=0.005). Systolic and diastolic blood pressure decreased significantly (P<0.01) in parallel to serum IL-6 levels (from 3.72+/-0.82 to 3.23+/-0.19 pg/ml, P=0.02) reaching a similar concentration to normotensive patients (3.33+/-0.3 pg/ml) after treatment with irbesartan. No significant changes were observed in any other of the tested parameters. In conclusion, the treatment of high blood pressure lowers circulating IL-6 in young hypertensive patients.
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PMID:Lowering of blood pressure leads to decreased circulating interleukin-6 in hypertensive subjects. 1575 24

Heparin-binding protein (HBP; CAP37/azurocidin) is secreted from neutrophil leukocytes early during inflammation and plays a central role in early capillary leakage and extravasation of neutrophils. Furthermore, HBP is chemotactic towards monocytes and lymphocytes and protects against stress-induced apoptosis, e.g. induced by oxygen radicals released during inflammation. Thus, administration of HBP as an adjunct to antibiotics increased survival of mice with peritonitis. In the present study, the effects of recombinant HBP as an adjunct to standard antibiotics were examined in a porcine model of Actinobacillus pleuropneumoniae-induced pneumonia. Beneficial and possible adverse effects of HBP were evaluated clinically and pathologically as well as by measurement of clinical chemical variables and markers of inflammation (interleukin-6 and C-reactive protein) and oxidative stress (ascorbic acid and alpha-tocopherol). Pigs receiving HBP (0.55 mgkg-1, n=11) as a 6-hourly subcutaneous infusion starting 1-h post-infection had a faster decrease in rectal temperature compared to control animals receiving a carrier-infusion (n=11), with a significant lower temperature at 32 h post-infection (p<0.05). This difference was, however, transient and the temperature curves had a similar course from 38 h and onwards. The transient effect of HBP might be explained by the dosage regimen that was used. No signs of adverse effects of the HBP-infusion were observed. More studies are needed to elucidate of the effects of HBP further and to optimise the dosage regimen for further improvement the efficacy and safety.
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PMID:Effects of heparin-binding protein (CAP37/azurocidin) in a porcine model of Actinobacillus pleuropneumoniae-induced pneumonia. 1582 30

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

Nearly half of the U.S. adult population is overweight or obese, which may be related to increased energy intake combined with lack of physical activity. Obesity increases the risk of several chronic diseases including diabetes, coronary heart disease, hypertension, and stroke. Conjugated linoleic acids (CLA) were shown to decrease fat and increase lean mass in several animal studies. However, the effects of CLA in combination with exercise (Ex) on body composition have not been studied in an animal model. We examined the effect of a low concentration of either safflower oil as control (0.5%) or mixed isomers of CLA (0.4%) along with treadmill exercise on body composition in male Balb/C mice fed a high-fat diet (20% corn oil) in a 2 x 2 factorial design. CLA consumption lowered change in fat mass (P < 0.001) confirming the results of other studies, and change in fat mass decreased further (P < 0.001) with CLA and exercise. Change in lean mass did not increase with exercise alone; it increased, although not significantly, with CLA alone and increased significantly (P < 0.05) due to the combination of CLA and exercise. This effect was accompanied by decreased serum leptin levels and lower leptin mRNA expression in peritoneal fat (P < 0.001). Serum insulin, glucose, tumor necrosis factor (TNF)-alpha, and interleukin-6 were lower in CLA-fed mice than in controls (P < 0.05), whereas serum TNF-alpha was increased by exercise (P < 0.05). Exercise increased oxygen consumption and energy expenditure when measured under resting conditions (P < 0.05). In summary, the combination of dietary CLA and exercise decreased fat mass and increased lean mass in mice fed a high-fat diet, and these effects may be related in part to decreased serum leptin and exercise-induced increases in oxygen consumption and energy expenditure.
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PMID:The combination of dietary conjugated linoleic acid and treadmill exercise lowers gain in body fat mass and enhances lean body mass in high fat-fed male Balb/C mice. 1586 92


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