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)

To assess whether the initial status of lipid metabolism in patients with chronic viral hepatitis might correlate with outcome of therapy, 52 patients (32 males and 20 female) with chronic hepatitis C were studied: 44 were treated with human recombinant interferon-alpha 2b (3 MU three times per week for up to 12 months), and 8 served as controls. At baseline, sera were tested for total and HDL cholesterol, HDL2, HDL3, apolipoprotein A-I, apolipoprotein B, interferon-alpha, tumor necrosis factor, and interleukin-6. Changes in blood lipids were evaluated after 3, 30, and 90 days of treatment. HDL cholesterol, apolipoprotein A-I, and HDL3 decreased by 9.4-11.4% within 4 weeks of starting interferon treatment, but this effect was sustained only in patients with a primary response to interferon. On multivariate analysis, a primary response to interferon correlated with higher apolipoprotein A-I and lower (< 2.23 pg/ml) interleukin-6 levels (p < 0.005 for both). In contrast, a sustained response was significantly more common in patients with low (< or = 13.3 pg/ml) serum interferon-alpha and lower interleukin-6 at baseline but did not correlate with any of the blood lipids. Thus, in chronic hepatitis C, interferon treatment induces specific changes in blood lipids. The concentration of apolipoprotein A-I at baseline is a strong predictor of primary response to treatment, and the likelihood of sustained response seems to be reflected by lower cytokine activation.
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PMID:Changes in blood lipid composition and response to interferon treatment in chronic hepatitis C. 852 43

Vascular access dysfunction is an important cause of morbidity for dialysis patients and a major contributor to hemodialysis cost. Thrombosis is a leading cause of vascular access failure, and usually results from stenotic lesions in the venous outflow system. This study was designed to explore the impact of serum levels of various risk factors for thrombosis and accelerated fibrointimal hyperplasia on progressive stenosis, and the subsequent thrombosis of hemodialysis fistula. A cross-sectional and 2-yr prospective pilot study was performed in 30 nondiabetic hemodialysis patients with primary arteriovenous fistula. Venous dialysis pressure, urea recirculation, color Doppler sonography, and angiography were used to monitor vascular access patency. Eleven patients (37%) developed a progressive stenosis in the venous circuit, which was complicated by thrombosis in three patients. Compared with the patients without fistula dysfunction, these patients had higher serum levels of monocyte chemoattractant protein-1 and interleukin-6, two cytokines that regulate the proliferation of vascular smooth muscle cells, which is the key mechanism in the pathogenesis of fistula stenosis. In addition, they had hyperinsulinemia, hyperlipidemia, and increased plasma levels of two hemostasis-derived risk factors for thrombosis: plasminogen activator inhibitor type 1 and factor VII. Monocyte chemoattractant protein-1, interleukin-6, plasminogen activator inhibitor type 1, factor VII, triglycerides, and the ratios for cholesterol/HDL-cholesterol, apolipoprotein (apo) A-I/ apo C-III, apo A-I/apo B, and glucose/insulin were independent predictors of fistula dysfunction. This study demonstrates the influece of cytokines, hemostasis-derived vascular risk factor, hyperinsullnemia, and abnormallties of lipids and apolipoproteins on primary fistula survival. The assessment of these factors might be useful for the identification of the patients at risk of fistula stenosis and thrombosis.
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PMID:Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. 886 9

In order to investigate whether a difference might exist in blood cholesterol and its subtractions between patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, serum cholesterol, HDL-cholesterol, triglycerides and common liver function tests were measured in 138 patients (92 male, 46 female) with biopsy-proven chronic viral hepatitis without cirrhosis. Twenty-four had hepatitis B and 114 hepatitis C. Mean serum cholesterol was lower in HCV-infected in comparison to HBV-infected patients (175 +/- 36 mg/dl vs. 189 +/- 28 mg/dl, p < 0.05). On multivariate analysis, etiology of hepatitis appeared to be associated with the value of serum cholesterol, independently of age, sex and liver synthetic function (improvement of chi-square 4.40, p < 0.05). In patients with HBV infection, circulating tumor necrosis factor-alpha demonstrated a correlation with serum triglycerides (p = 0.618) and an inverse correlation with serum HDL-cholesterol (p = -0.456); in the group of patients with HCV infection, interleukin-6 correlated with triglycerides (p = 0.370) and HDL-cholesterol (p = -0.355). Thus, differences in the mechanisms of liver damage and of viral clearance in hepatitis C in comparison to hepatitis B, reflected in these patients by the levels of circulating cytokines, may be mirrored by differences in their blood lipid composition.
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PMID:Blood lipids of patients with chronic hepatitis: differences related to viral etiology. 920 35

Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertriglyceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated acute-phase/stress reactants (the innate immune system's response to environmental stress) and their major cytokine mediator (interleukin-6, IL-6) are associated with NIDDM and syndrome X, and may thus provide a unifying pathophysiological mechanism for these conditions. Two groups of Caucasian subjects with NIDDM were studied. Those with any 4 or 5 features of syndrome X (n = 19) were compared with a group with 0 or 1 feature of syndrome X (n = 25) but similar age, sex distribution, diabetes duration, glycaemic control and diabetes treatment. Healthy non-diabetic subjects of comparable age and sex acted as controls. Overnight urinary albumin excretion rate, a risk factor for cardiovascular disease, was also assayed in subjects to assess its relationship to the acute-phase response. Serum sialic acid was confirmed as a marker of the acute-phase response since serum concentrations were significantly related to established acute-phase proteins such as alpha-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, alpha-1 acid glycoprotein, IL-6 and urinary albumin excretion rate amongst the three groups, with the lowest levels in non-diabetic subjects, intermediate levels in NIDDM patients without syndrome X and highest levels in NIDDM patients with syndrome X. C-reactive protein and cortisol levels were also higher in syndrome X-positive compared to X-negative patients and serum amyloid A was higher in both diabetic groups than in the control group. We conclude that NIDDM is associated with an elevated acute-phase response, particularly in those with features of syndrome X. Abnormalities of the innate immune system may be a contributor to the hypertriglyceridaemia, low HDL cholesterol, hypertension, glucose intolerance, insulin resistance and accelerated atherosclerosis of NIDDM. Microalbuminuria may be a component of the acute-phase response.
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PMID:NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. 2212 8

In a previous retrospective study, we reported a significant reduction in serum cholesterol levels following major surgery, and speculated on the possible role of cytokines in this reduction. The purpose of this article is to report a prospective study of the association of cytokines with postoperative changes in serum lipoprotein levels. Serum samples were obtained from 11 male patients before and at intervals for up to 10 days after surgery, and were assayed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), cortisol, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interferon-gamma (IFN-gamma). LDL-C was calculated. The TC showed a 27.9% decrease, from a mean of 4.27 mmol/L to 3.08 mmol/L (p < 0.001) after surgery, reaching a nadir at 24 hours and returning to preoperative values in 7 to 10 days. A similar decrease was noted in the HDL-C and LDL-C levels. IL-6 levels increased from a mean baseline value of 6 pg/ml to a peak of 143 pg/ml at 24 hours (p < 0.0006). There was an inverse relationship between TC and IL-6 levels, with r = -0.51 for the entire curve and r = -0.90 for the cholesterol nadir with the IL-6 peak. The other cytokines did not show significant changes. We conclude that TC and its fractions decrease to a nadir and that IL-6 increases to a peak approximately 24 hours after major surgery. There is a significant inverse correlation between TC and IL-6, suggesting a possible role of IL-6 in postoperative changes in serum lipoproteins.
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PMID:Postsurgical reduction of serum lipoproteins: interleukin-6 and the acute-phase response. 945 33

Type II (non-insulin-dependent) diabetes mellitus is associated with increased blood concentrations of markers of the acute-phase response, including sialic acid, alpha-1 acid glycoprotein, serum amyloid A, C-reactive protein and cortisol, and the main cytokine mediator of the response, interleukin-6. The dyslipidaemia common in Type II diabetes (hypertriglyceridaemia and low serum levels of HDL cholesterol) is also a feature of natural and experimental acute-phase reactions. We review evidence that a long-term cytokine-mediated acute-phase reaction occurs in Type II diabetes and is part of a wide-ranging innate immune response. Through the action of cytokines on the brain, liver, endothelium, adipose tissue and elsewhere, this process could be a major contributor to the biochemical and clinical features of metabolic syndrome X (glucose intolerance, dyslipidaemia, insulin resistance, hypertension, central obesity, accelerated atherosclerosis) but also provides a mechanism for many other abnormalities seen in Type II diabetes, including those in blood clotting, the reproductive system, metal ion metabolism, psychological behaviour and capillary permeability. In the short-term, the innate immune system restores homeostasis after environmental threats; we suggest that in Type II diabetes and impaired glucose tolerance long-term lifestyle and environmental stimulants, probably in those with an innately hypersensitive acute-phase response, produce disease instead of repair.
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PMID:Is type II diabetes mellitus a disease of the innate immune system? 1023 Jun 57

Haemorheological variables (whole-blood, plasma and relative blood viscosity, haematocrit, red cell aggregation, white cell count and fibrinogen) were measured in 753 men and 821 women aged 25-74 years, and related to cardiovascular risk factors and prevalent cardiovascular disease (CVD). Men had higher levels than women of blood viscosity, haematocrit, corrected viscosity and relative viscosity. Post-menopausal women had higher levels than pre-menopausal women of blood viscosity, haematocrit, corrected blood viscosity, plasma viscosity and fibrinogen: each of these differences was completely or partly abolished by use of hormone replacement therapy. Serum total cholesterol, triglycerides, diastolic blood pressure, body mass index and smoking markers showed positive associations with most rheological variables, whereas HDL-cholesterol, plasma vitamin C and social class showed inverse associations. Rheological variables were associated with prevalent CVD after age-adjustment. However, after multiple risk factor adjustment only plasma viscosity and red cell aggregation showed significant (P<0.04) associations in both men and women (comparing top to bottom quarters). Plasma interleukin-6 (measured in a 25% subsample of 196 men and 221 women) correlated significantly with age, fibrinogen, white cell count, plasma and blood viscosity, current smoking, and (in men) with low serum vitamin C levels; but not with other major risk factors or with prevalent cardiovascular disease.
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PMID:Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease. 1005 Jul 4

C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease.
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PMID:C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? 1019 25

There is mounting evidence that inflammation plays a role in the development of coronary heart disease (CHD). Observations have been made linking the presence of infections in the vessel wall with atherosclerosis, and epidemiological data also implicate infection in remote sites in the aetiology of CHD. In this article we propose a key role for the proinflammatory cytokine interleukin-6 (IL-6) in several mechanisms that contribute to the development of CHD. IL-6 is a powerful inducer of the hepatic acute phase response. Elevated concentrations of acute phase reactants, such as C-reactive protein (CRP), are found in patients with acute coronary syndromes, and predict future risk in apparently healthy subjects. The acute phase reaction is associated with elevated levels of fibrinogen, a strong risk factor for CHD, with autocrine and paracrine activation of monocytes by IL-6 in the vessel wall contributing to the deposition of fibrinogen. The acute phase response is associated with increased blood viscosity, platelet number and activity. Furthermore, raised serum amyloid A lowers HDL-cholesterol levels. IL-6 decreases lipoprotein lipase (LPL) activity and monomeric LPL levels in plasma, which increases macrophage uptake of lipids. In fatty streaks and in the atheromatous 'cap' and 'shoulder' regions, macrophage foam cells and smooth muscle cells (SMC) express IL-6, suggesting a role for this cytokine along with interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha), in the progression of atherosclerosis. Both these cytokines induce the release of IL-6 from several cell types, including SMC. During vascular injury SMC are exposed to platelets or their products, and cytokine production by SMC further contributes to vascular damage. Furthermore, circulating IL-6 stimulates the hypothalamic-pituitary-adrenal (HPA) axis, activation of which is associated with central obesity, hypertension and insulin resistance. Thus we propose a role for IL-6 in the pathogenesis of CHD through a combination of autocrine, paracrine and endocrine mechanisms. This hypothesis lends itself to testing using interventions to influence IL-6 secretion and actions.
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PMID:Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? 1065 56

The current understanding of the origin of atherosclerosis is that of an inflammatory process that involves the acute phase response -an innate biological response to a disturbance in homeostasis -infection, inflammation, tissue injury, neoplasm, or immune disturbance. The activation of the acute phase response, signaled by interleukin-6, produces proteins (fibrinogen, C-reactive protein (CRP), serum amyloid A) that lead to inflammatory reactions. The tissues themselves contain elevated levels of acute phase proteins and cytokines resulting in a localized inflammatory effect. Localized inflammatory responses in the intimal layer of the arterial wall have been shown to be responsible for many of the aspects of intimal thickening and plaque disruption, leading to acute cardiovascular events. The predictive value of plasma C-reactive protein as a risk factor for cardiovascular events has led some researchers to support the use of CRP as a main cardiovascular risk assessment tool, along with total cholesterol:HDL ratios and homocysteine levels. The ability of HMG-CoA reductase inhibitors to lower C-reactive protein levels has recently brought into question the mechanisms of action of the statin drugs. Because these medications lower incidences of acute cardiovascular events as well as decreasing morbidity and mortality well before the effects of lowered LDL cholesterol can be expected to occur, questions have been asked about whether they may work independently of LDL-lowering mechanisms. Red yeast rice contains a naturally-occurring statin (lovastatin) as well as other cholesterol-lowering compounds, some with antioxidant effects. Alpha-tocopherol also significantly lowers CRP levels in diabetics and nondiabetics, and minimizes other aspects of the acute phase response and inflammatory damage involved in atherosclerosis. This may account for alpha-tocopherol's positive effect on cardiovascular morbidity and mortality. Finally, polyphenolic compounds present in virgin olive oil also have anti-inflammatory and antioxidative effects in cardiovascular disease. The phenolic compounds in virgin olive oil may explain some of the protective effects found in epidemiological studies.
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PMID:Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. 1141 71


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