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 clarify the relationship between cholesterol homeostasis and inflammation we studied the effect of hypercholesterolaemia on in vivo cytokine production and leukocyte migration, in a murine model of local inflammation. Hypercholesterolaemia reduced of 40% the leukocyte recruitment by inhibiting interleukin-6 and monocyte chemotactic protein-1 production in the pouch exudate, without affecting vascular permeability or leukocytes motility.
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PMID:Inhibition of HMG-CoA reductase activity by hypercholesterolaemia reduces leukocyte recruitment and MCP-1 production. 1088 Feb 57

Interleukin-6 (IL-6) gene expressed in bone marrow-derived stromal cells and osteoblasts contributes to the state of mineralization and its control by estradiol may be involved in the development of post-menopausal osteoporosis. Since IL-6 is also expressed in the different cell populations of the arterial wall, the purpose of this study was to gain more insight into its involvement in the atherosclerotic process and the atheroprotective effect of estradiol by studying double deficient mice at the apolipoprotein E and IL-6 loci (IL-6(-/-)/E(-/-)). At 1 year of age, IL-6(-/-)/E(-/-) mice showed similar hypercholesterolemia to IL-6(+/+)/E(-/-) mice but presented significantly larger and more calcified lesions. In younger mice (sixteen weeks of age), no significant difference in fatty streaks could be detected in IL-6(+/+)/E(-/-), IL-6(+/-)/E(-/-) and IL-6(-/-)/E(-/-) mice on a normal chow diet. Estrogen supplementation at this age induced a decrease of fatty streak formation in all three genotypes. The combined data indicate that IL-6 expression is involved at the fibrous plaque stage of the atherosclerotic process but does not constitute a direct target for estradiol to prevent fatty streak formation.
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PMID:Involvement of interleukin-6 in atherosclerosis but not in the prevention of fatty streak formation by 17beta-estradiol in apolipoprotein E-deficient mice. 1139 27

Atherosclerotic plaques were likened histologically to healing inflammatory lesions by Russell Ross, who proposed a "response to injury" hypothesis for their formation. More recently, intraplaque inflammation has been postulated to play a role in thinning of the fibrous cap, plaque rupture, and superadded thrombosis. Potential causes for vascular injury include mechanical stress, smoke exposure, hypercholesterolemia, hyperhomocysteinemia, and chronic infection (direct, or indirect). Blood levels of inflammatory markers (e.g., C-reactive protein [CRP]; serum amyloid A [SAA]; fibrinogen; plasma viscosity; erythrocyte sedimentation rate [ESR]; leukocyte count, low serum albumin) have been associated with vascular risk factors and with prevalent and incident atherothrombotic cardiovascular disease (CVD) (coronary heart disease, [CHD]; stroke; and peripheral arterial disease). More recently, cytokines (e.g., interleukin-6 [IL-6]) and soluble adhesion molecules (e.g., intercellular adhesion molecule-1, vascular cell adhesion molecule-1) have been associated with both risk factors and disease; and offer potential therapeutic targets for nonspecific "anti-inflammatory" treatment of arterial disease. Infections associated with arterial disease include specific infections (Chlamydia pneumoniae, Helicobacter pylori) and nonspecific infections (periodontal infections, respiratory tract infections). Recent meta-analyses have shown that associations of serum markers of C. pneumoniae and H. pylori with arterial disease, risk factors, or potential intermediary mechanisms for disease are weaker than was first suggested by early reports. Likewise, further studies and meta-analyses are required to evaluate the epidemiologic relationships of CVD to periodontal infection and disease and to chronic pulmonary infections and disease. The weaker the associations between chronic infections and CVD, the larger is the size of randomized controlled trials required to establish (or exclude) a preventive effect of infection treatment. While control of chronic infection in the mouth, stomach or lungs is appropriate for its local effects, proving its efficacy in prevention of CVD presents a continuing challenge to medical science.
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PMID:The relationship between infection, inflammation, and cardiovascular disease: an overview. 1188 52

In the present study, we compared the effect of atorvastatin (1 mg.kg(-1).day(-1)) and quinapril (0.5 mg.kg(-1).day(-1)) alone or in combination on inflammatory markers, endothelial function, intimal thickening and fibrinolytic balance in rabbits fed with either a control diet or a diet containing 1% (v/v) cholesterol for 12 weeks. Atorvastatin alone or in combination partially prevented the increase in cholesterol plasma levels observed in rabbits fed with the cholesterol-rich diet, but did not modify blood pressure levels. Quinapril administration did not alter any of these parameters in any group. Hypercholesterolaemia increased plasma levels of interleukin-1beta, interleukin-6, interferon-gamma and C-reactive protein, reduced acetylcholine-induced relaxation and produced intimal thickening. Likewise, atherosclerotic rabbits had reduced plasma tissue-type plasminogen activator activity and D-dimer levels and an increase in plasminogen-activator inhibitor-1 activity. Both drugs enhanced acetylcholine-induced relaxation, reduced intimal thickening and improved fibrinolytic balance in atherosclerotic rabbits in a similar manner. Their combination did not induce additive effects on these parameters. However, only the combination of both drugs was able to prevent the increase in inflammatory markers induced by hypercholesterolaemia. In summary, these data suggest that quinapril and atorvastatin had comparable beneficial effects on the alterations of vascular function and structure as well as fibrinolytic balance in atherosclerotic rabbits. In addition, the combination of atorvastatin and quinapril exerts a synergistic effect on inflammatory markers, which individual treatment, at the doses used, was not able to modify.
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PMID:Synergistic effect of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibition on inflammatory markers in atherosclerotic rabbits. 1284 17

Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.
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PMID:Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin. 1513 69

Hypercholesterolemia causes endothelial dysfunction, an early feature of atherosclerosis, leading to increased production of adhesion molecules and cytokines. The aim of this study was to investigate the effects of three months of treatment with low dose atorvastatin on serum levels of adhesion molecules, interleukin-6 (IL-6) and highly sensitive C-reactive protein (hs-CRP) in patients with non-familial hypercholesterolemia. Fifty-five patients with non-familial hypercholesterolemia were randomized to treatment with atorvastatin 10 mg/day or placebo for 3 months. Soluble intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, IL-6 and hs-CRP levels were measured to assess the inflammatory activity of the endothelium. There was a significant reduction in ICAM-1 at 2 weeks (p<0.0001) with further reduction at 3 months (p<0.0001). At 3 months, there were significant reductions in VCAM-1 (p<0.02), IL-6 (p<0.0001) and hs-CRP (p<0.01), but an increase in E-selectin levels (p<0.002). Treatment with statin was an independent determinant of change in ICAM-1 (p<0.05) and IL-6 levels (p<0.05) after correcting for anthropometric indices, blood pressure and lipid profile. Low-dose atorvastatin treatment leads to reduction in proinflammatory markers of endothelial function, suggesting an attenuation of endothelial activation and improvement in endothelial function, independent of lipid lowering. This may lead to a reduction in the progression of atherosclerosis.
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PMID:Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia. 1295 65

I investigated whether metabolism of essential fatty acids and the concentrations of their long-chain metabolites (long-chain polyunsaturated fatty acids [LCPUFAs]) are altered in fetal or perinatal growth retardation, maternal hypercholesterolemia, low-grade systemic inflammation, insulin resistance, and atherosclerosis, conditions that predispose to the development of coronary heart disease (CHD).I critically reviewed the literature pertaining to the metabolism of essential fatty acids in CHD and conditions that predispose to it.LCPUFAs enhance endothelial nitric oxide synthesis, suppress the production of the proinflammatory cytokines tumor necrosis factor and interleukin-6, attenuate insulin resistance, and have antiatherosclerotic properties. Low-birthweight infants have decreased concentrations of LCPUFAs, especially arachidonic acid. Neonatal arachidonic acid status is related to intrauterine growth, and LCPUFAs improve fetal and postnatal growth. LCPUFAs are useful in the management of hyperlipidemia, inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and may mediate the beneficial actions of statins. Plasma concentrations of various LCPUFAs are low in diabetes mellitus, hypertension, and CHD and in populations at high risk of CHD. Breast milk is rich in LCPUFAs, and this may explain why and how adequate (6 mo to 1 y) breast feeding protects against the development of obesity, hypertension, insulin resistance, and CHD.LCPUFAs are essential for the growth and development of the fetus and infant. LCPUFAs can prevent various conditions that predispose to the development of CHD. The low incidence of CHD seen in adequately breast-fed infants can be linked to the LCPUFA content of breast milk. Based on this evidence, I suggest that provision of LCPUFAs during critical periods of growth, especially from the second trimester of pregnancy to age 5 y, prevents CHD in adult life.
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PMID:A perinatal strategy to prevent coronary heart disease. 1462 57

Protein-energy malnutrition (PEM) and inflammation are common in patients with chronic kidney disease (CKD) and worsen as the CKD progresses toward the end-stage renal disease (ESRD). These conditions are major predictors of poor clinical outcome in kidney failure, as reflected by a strong association between hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that inflammation is the cause of both PEM and CVD and, hence, the main link among these conditions, but these hypotheses are not well established. Increased release or activation of inflammatory cytokines, such as interleukin-6 or tumor necrosis factor alpha, may suppress appetite, cause muscle proteolysis and hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of proinflammatory cytokines caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions may lead to inflammation in CKD patients. In hemodialysis patients, the exposure to dialysis tubing and dialysis membranes, poor quality of dialysis water, back-filtration or back-diffusion of contaminants, and foreign bodies in dialysis access maybe additional causes of inflammation. Similarly, episodes of overt or latent peritonitis, peritoneal dialysis (PD) catheter and its related infections, and constant exposure to PD solution may contribute to inflammation in these patients. The degree to which PEM in dialysis patients is caused by inflammation is not clear. Because both PEM and inflammation are strongly associated with each other and can change many nutritional measures and outcome concurrently in the same direction, the terms malnutrition-inflammation complex syndrome (MICS) and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to denote the important contribution of both of these conditions to poor clinical outcome. Maintenance dialysis patients who are underweight or who have low serum levels of cholesterol, creatinine, or homocysteine may be suffering from the MICS/MIA and its subsequent poor outcome. Consequently, obesity and hypercholesterolemia may appear protective, which is known as reverse epidemiology. Although MICS/MIA may have a significant contribution in reversing the traditional CVD risk factors in dialysis patients, it is not clear whether PEM or inflammation and their complications can be effectively managed in CKD and ESRD or whether their management improves clinical outcome.
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PMID:Inflammation and nutrition in renal insufficiency. 1470 70

By the turn of the last century, flying in the face of over a hundred years of research and clinical observation to the contrary, medicine abandoned the link between infection and atherogenesis; not because it was ever proven wrong, but because it did not fit in with the trends of a medical establishment convinced that chronic disease such as heart disease must be multifactorial, degenerative and non-infectious. Yet it was the very inability of 'established' risk factors such as hypercholesterolemia, hypertension and smoking to completely explain the incidence and trends in cardiovascular disease that resulted in historically repeated calls to search out an infectious cause, a search that began more than a century ago. Today, half of US heart attack victims have acceptable cholesterol levels and 25% or more have none of the "risk factors" associated with heart disease, including smoking, high blood pressure or obesity, most of which are not inconsistent with being caused by infection. Even the case of the traditionalist's latest 2003 JAMA assault to 'debunk' what they call the "50% risk factor myth" falls woefully short under scrutiny. In one group 30% died of heart disease with a cholesterol of at least 240 mg/dl, a condition which also existed in 21% who did not die during the same period. And the overlap was obvious throughout the so-called risk categories. Under such scrutiny, lead author Greenland conceded that if obesity, inactivity and elevated cholesteriol in the elderly are included, just about everyone has a risk factor and he likened the dilemma of people who do or do not wind up with heart disease akin to the susceptibility of people who are exposed to tuberculosis but do not get the disease. In Infections and Atherosclerosis: New Clues from an old Hypothesis? Nieto stressed the need to extend the possible role of infectious agents beyond the three infections which have in recent years been the focus of research: Cytomegalovirus (CMV) Chlamydia pneumoniae and Helicobactor pylori. Mycobacterial disease shares interesting connections to heart disease. Not only is tuberculosis the only microorganism to depend on cholesterol for its pathogenesis but CDC maps for cardiovascular disease bear a striking similarity to those of State and regional TB case rates. Ellis, Hektoen, Osler, McCallum, Swartz, Livingston and Alexander-Jackson all saw clinical and laboratory evidence of a causative relationship between the mycobacteria and heart disease. And Xu showed that proteins of mycobacterial origin actually led to experimental atherosclerosis in laboratory animals Furthermore present day markers suggested as indicators for heart disease susceptibility such as C-Reactive Protein (CRP), interleukin-6 and homocysteine are all similarly elevated in tuberculosis. It therefore behooves us to explore the link between heart disease and typical and atypical tuberculosis.
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PMID:Heart disease: the greatest 'risk' factor of them all. 1508 5

In this prospective study, we aimed to evaluate the effect of simvastatin on bone metabolism and the correlation between changes in bone turnover parameters and serum cytokine levels. For this purpose, 38 postmenopausal subjects with hypercholesterolemia (>240 mg/dl), not on osteoporosis treatment, were studied. Simvastatin was started at a dose of 20 mg daily and continued for 3 months. Six patients were excluded from the study during the follow-up period. Pre- and post-treatment samples were analyzed for bone alkaline phosphatase (BAP) and osteocalcin (OCL), as markers of bone formation; for carboxyterminal telopeptide of collagen I (CTX), as a marker of bone resorption; and for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) cytokine levels. Total cholesterol level was decreased from 262.1 +/- 30.9 to 210.2 +/- 35.6 mg/dl after simvastatin treatment (P < 0.0001). While no significant change was observed in serum CTX level, BAP and OCL levels were significantly increased (from 120.8 +/- 56.6 to 149.5 +/- 57.6 IU/l [P = 0.008], and from 20.8 +/- 12.6 to 34.7 +/- 18.4 microg/l [P = 0.015], respectively). In the analysis of cytokines, while no significant change was observed in IL-6 levels, the TNF-alpha level was found to be significantly decreased after simvastatin treatment (from 77.9 +/- 31.6 pg/ml to 23.5 +/- 12.6 pg/ml [P = 0.021]). Individual changes in TNF-alpha levels showed a moderate negative correlation with the individual changes in BAP and OCL levels (r = -0.550 [P = 0.001], and r = -0.497 [P = 0.004], respectively). In conclusion; 20-mg daily simvastatin treatment for 3 months significantly increased BAP and OCL levels (markers of bone formation) in hypercholesterolemic postmenopausal subjects, without affecting bone resorption. These findings support the idea that simvastatin has an anabolic effect on bone formation. Additionally, the presence of a negative correlation between TNF-alpha levels and the anabolic bone parameters suggests that a cytokine-lowering effect of simvastatin may also be involved in the remodeling process and could exert some additive beneficial effect on bone metabolism.
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PMID:The effect of simvastatin on serum cytokine levels and bone metabolism in postmenopausal subjects: negative correlation between TNF-alpha and anabolic bone parameters. 1522 96


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