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)

Chronic neuroinflammation correlates with cognitive decline and brain atrophy in Alzheimer's disease (AD), and cytokines and chemokines mediate the inflammatory response. However, quantitation of cytokines and chemokines in AD brain tissue has only been carried out for a small number of mediators with variable results. We simultaneously quantified 17 cytokines and chemokines in brain tissue extracts from controls (n = 10) and from patients with and without genetic forms of AD (n = 12). Group comparisons accounting for multiple testing revealed that monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) were consistently upregulated in AD brain tissue. Immunohistochemistry for MCP-1, IL-6 and IL-8 confirmed this increase and determined localization of these factors in neurons (MCP-1, IL-6, IL-8), astrocytes (MCP-1, IL-6) and plaque pathology (MCP-1, IL-8). Logistic linear regression modeling determined that MCP-1 was the most reliable predictor of disease. Our data support previous work on significant increases in IL-6 and IL-8 in AD but indicate that MCP-1 may play a more dominant role in chronic inflammation in AD.
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PMID:Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease. 1863 12

An increased serum interleukin-6 (IL-6) level is associated with an increased risk of cardiovascular events in healthy subjects. However, it is unknown whether the level of serum IL-6 or genetic IL-6 polymorphism is correlated with the complexity of coronary plaque in patients with stable coronary artery disease (CAD). Patients with stable CAD (n = 135) were divided into 3 groups: insignificant coronary plaque (n = 77), simple coronary plaque (n = 15), and complex coronary plaque (n = 43). IL-6-174G > C polymorphism and serum levels of IL-6 and C-reactive protein (CRP) were investigated. No significant difference in the distribution of IL-6 genotypes was found among the groups. The presence of complex coronary plaque was associated with higher serum concentrations of IL-6 (P = 0.026) and CRP (P < 0.0001). To predict the presence of complex lesions, IL-6 > 5.8 ng/L and CRP > 2.6 mg/L had sensitivities of 86% and 74%, and specificities of 61% and 62%, respectively. By multivariate analysis, IL-6 > 5.8 ng/L and CRP > 2.6 mg/L were independently related to the presence of complex coronary plaque (P = 0.0002 and 0.004, respectively). IL-6 > 5.8 ng/L and CRP > 2.6 mg/L were associated with a 4.5-fold increase in the odds of having complex coronary plaque (P < 0.005). A simple measurement of the serum IL-6 level in patients with CAD can potentially identify subjects with complex coronary lesions and provide the option of aggressive medical strategies in a clinical setting.
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PMID:Serum interleukin-6 levels, not genotype, correlate with coronary plaque complexity. 1875 23

The predisposition to thrombogenesis is increased in essential hypertension, and hypertensive patients are prone to develop more vulnerable atherosclerotic plaques. To evaluate the possible influence of family history of hypertension on some indicators of early atherosclerosis, we studied eighty-five healthy normotensive individuals with (FH+) or without (FH-) family history of essential hypertension by measuring metabolic profile and concentrations of P-selectin, interleukin 6 and matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1. In a subset of individuals, MMP-9 activity was assessed in monocytes by zymography, and TIMP-1 expression by western blot. As compared with FH- individuals, FH+ individuals had significantly higher P-selectin but similar interleukin-6 levels. Although no difference was observed in MMP-2 levels between the two groups, MMP-9 and TIMP-1 were higher in FH+ individuals, who also had higher intracellular MMP-9 levels and TIMP-1 protein expression. P-selectin (r=-0.32; P<0.01), MMP-9 (r=-0.37; P<0.001) and TIMP-1 (r=-0.23; P<0.05) levels were inversely related to high density lipoprotein (HDL) cholesterol. P-selectin was also directly related to serum triglycerides (r=0.30; P<0.01). We conclude that a positive family history of hypertension is associated with an initial increase in markers of inflammation and plaque instability in otherwise healthy young normotensive individuals, likely conveying a predisposition to develop early atherothrombosis.
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PMID:Family history of hypertension, anthropometric parameters and markers of early atherosclerosis in young healthy individuals. 1933 95

The regulatory mechanisms of the inflammatory process in the atherosclerotic plaque are still not clearly understood. Stimulated T cells may have a key role in enhancing and perpetuating inflammation at the atherosclerotic site. They activate endothelial cells, macrophages and smooth muscle cells in the atherosclerotic plaque, not only via the production of soluble mediators, but also through cell-cell contact-mediated interactions (via membrane receptors and their ligands). Cell/cell contact between stimulated T lymphocytes and monocytes/macrophages and endothelial cells induces the production of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) and chemokines (interleukin-8, monocyte chemotactic factor-1). Thus, these interactions could play a relevant role in the disregulation of the inflammatory process in the atherosclerotic plaque, representing a novel mechanism of progression and complication of the atherosclerotic disease. Understanding the key ligands and receptors involved may permit the definition of new therapeutic targets.
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PMID:[Cellular mechanisms of regulation of the inflammatory response in atherosclerosis: the role of cell contact-mediated signaling]. 1939 4

Despite high efficacy of percutaneous coronary intervention (PCI), in-stent restenosis proves to be a significant problem of therapy. Restenosis concerns around 30 percent of patients. Studies have suggested that restenosis is initiated by cells which participate in intense inflammatory reaction caused by stent implantation. Atherosclerotic plaque rupture during stent implantation and PCI-associated injury of the vessel wall lead to hemorrhage and release of various cytokines. They are probably responsible for quick recurrence of vascular lumen stenosis (restenosis). Interleukin-6 (IL-6) is known as a main pro-inflammatory cytokine, whereas Transformig Growth Factor-beta1 (TGF-beta1) has anti-inflammatory properties. The study population comprised 36 patients with myocardial infarction treated with PCI with stent implantation. They underwent control coronary angiography after 12 months. At this time plasma concentration of IL-6 and TGF-beta was measured in peripheral blood. Serum IL-6 concentration in the analyzed population correlates with lumen loss (p<0.01) and the severity of stenosis (p<0.001). No such correlation was found between serum TGF-beta1 concentration and lumen loss (p=NS) or the severity of stenosis (p=NS). The IL-6 plasma concentration may be a marker of in-stent restenosis in patients after PTCA, while the concentration of TGF-beta1 is not associated with the occurrence of restenosis at one year of follow-up.
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PMID:The role of interleukin-6 and transforming growth factor-beta1 in predicting restenosis within stented infarct-related artery. 1950 1

Female cynomolgus monkeys are excellent models for understanding cardiovascular disease and the relationships between inflammatory processes and conditions such as atherogenesis. This review summarizes published research findings obtained through comprehensive, multidisciplinary, multi-investigator studies in nonhuman primates over the past two decades. These studies examined the effects of exogenous estrogens and dietary soy protein/isoflavones (IFs) on atherosclerosis, circulating biomarkers, and tissue inflammation in pre- and postmenopausal female cynomolgus monkeys. Inflammation may play a role in the initiation and progression of disease, be a consequence of the disease, or both. Circulating and tissue biomarkers with inflammatory and anti-inflammatory characteristics (including adhesion molecules such as e-selectin, VCAM-1, and ICAM-1, chemokines such as MCP-1, cytokines such as interleukins, and acute phase reactants such as CRP, and others) may be useful indicators of disease status. Treatment of postmenopausal subjects with estrogen resulted in significant reductions in several key inflammatory mediators as well as atherosclerosis, while dietary IF had a more limited effect on inflammation and atherogenesis. Circulating concentrations of key inflammatory proteins, including monocyte-chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), were associated with atherosclerosis and lesion characteristics in these animals. In premenopausal female monkeys, a diet enriched in soy protein reduced arterial inflammation as well as atherogenesis in comparison to a diet enriched in casein-lactalbumin. Expression levels of arterial inflammation associated genes (MCP-1, ICAM-1) and markers for inflammatory cell types (macrophages and T cells) correlated with plaque size, were differentially influenced by treatments, and represent potential targets for interventions. Arterial expression of estrogen receptor alpha, the key mediator of estrogenic effects, was inversely correlated with plaque size and indices of inflammation, suggestive of an atheroprotective role. The findings provide additional evidence that circulating inflammatory markers (particularly MCP-1) may be useful indicators of atherosclerotic disease progression and responses to treatment in female primates, and that estrogens and dietary soy may inhibit atherogenesis in part through anti-inflammatory mechanisms.
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PMID:Primate models in women's health: inflammation and atherogenesis in female cynomolgus macaques (Macaca fascicularis). 1953 Jan 26

The importance of inflammation as a driver of pathology is no longer confined to autoimmune and infectious diseases. In line with convincing experimental data as well as abundant clinical findings the current view of atherosclerosis points to inflammation as a critical regulator of atherosclerotic plaque formation and progression leading to the fatal clinical endpoints myocardial infarction, stroke or sudden cardiac death. The underlying mechanisms have been a matter of intense research during the last decades. In this regard, the interleukin-6 (IL-6) cytokines and their signalling events have been shown to contribute to both, atherosclerotic plaque development and plaque destabilisation via a variety of mechanisms. These involve the release of other pro-inflammatory cytokines, oxidation of lipoproteins by phospholipases, stimulation of acute phase protein secretion, the release of prothrombotic mediators, and the activation of matrix metalloproteinases. Moreover, the formation of reactive oxygen species generated by vascular enzyme systems may play a critical role in the regulation of IL-6 indicating a cross talk between vasoactive substances i.e. angiotensin II or adrenalin and pro-inflammatory cytokines such as IL-6. In this review we will summarise and discuss the underlying molecular and cellular mechanisms how IL-6 as an early and central regulator of inflammation contributes to atherosclerosis and how this knowledge can be integrated into the clinical context.
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PMID:How much is too much? Interleukin-6 and its signalling in atherosclerosis. 1965 71

The cardioprotective effects of food rich in omega-3 (omega-3) polyunsaturated fatty acids (PUFA) on cardiovascular risk has been of interest from the moment when a low rate of coronary heart disease was documented in the Eskimo population. The aim of the present review is to discuss recent studies documenting multidirectional action of omega-3 PUFA due to its pleiotropic properties. Experimental studies in cellular and animal models have extensively documented the favorable effects of omega-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) on: inflammatory processes, endothelial dysfunction, platelet aggregation and arrhythmogenesis. It was reported that antiarrhythmic effects of omega-3 PUFA resulted from stabilization of cardiomyocyte membrane and inhibition of ion channels. Moreover, PUFA possess several pleiotropic properties i.e. anti-inflammatory, anti-atherogenic and antithrombotic. Anti-atherogenic effects (plaque stabilization) of omega-3 PUFA have recently been demonstrated. It was documented (OCEAN study) that eicosapentaenoic acid from a source of highly purified ethyl esters is incorporated into plaques in a relatively short period of time and these higher concentrations of omega-3 PUFA may stabilize vulnerable atherosclerotic plaques. The anti-inflammatory effect of omega-3 PUFA is associated with reduction of levels of TNF-alpha and interleukin-6. Eicosapentaenoic acid and docosahexaenoic acid inhibit arachidonic acid metabolism to inflammatory eicosanoids.
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PMID:Pleiotropic, cardioprotective effects of omega-3 polyunsaturated fatty acids. 1968

Obesity, particularly abdominal adiposity, is increasingly recognized as a cause of elevated cardiometabolic risk--the risk of developing type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). The predominate mechanisms appear to involve the promotion of insulin resistance, driven largely by excess free fatty acids secreted by an expanded adipose tissue mass, and the development of an inflammatory milieu due to increased secretion of inflammatory cytokines and adipokines from adipose tissue. Key proinflammatory cytokines secreted by adipocytes include tumor necrosis factor-alpha, interleukin-6, leptin, resistin, and plasminogen activator inhibitor-1. All have been variously associated with hyperinsulemia, hyperglycemia, insulin resistance, diabetes, and endothelial dysfunction, as well as plaque development, progression, and rupture. Adiponectin, another important adipocyte, has protective cardiometabolic actions; however, adiponectin levels decline with increasing obesity. Understanding the role of obesity in the pathogenesis of cardiometabolic risk is crucial for the development of treatment strategies that will provide maximum benefit for patients with, or at risk for, type 2 DM and CVD.
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PMID:Overweight and obesity: the pathogenesis of cardiometabolic risk. 1978 62

Considerable progress has been made in the understanding of atherogenesis and atherosclerosis is now considered to be an inflammatory disease of the vessel wall involving several cell types, such as endothelial cells, smooth muscle cells and macrophages. Progression of an atheroslerotic lesion can lead to vulnerable and rupture-prone plaques, causing thrombus formation and the development of acute coronary syndromes. The balance between inflammatory (e.g., tumor necrosis factor-alpha, interleukin-6,) and anti-inflammatory cytokines (e.g., IL-10) seems to be of critical importance in the pathogenesis of plaque formation and destabilization, and it has recently been suggested that an inflammatory imbalance in unstable disease with inadequately raised IL-10 levels is also of importance. This lack of IL-10-mediated responses could promote inflammation, enhance oxidative stress and foam cell apoptosis, leading to plaque destabilization and thrombus formation and the development of acute coronary syndromes. Based on these issues, IL-10 has been postulated as an immunological scalpel in atherosclerotic disorders. Knowledge of IL-10 as a modulator of plaque stability may provide multiple opportunities for the treatment and prevention of atherosclerotic diseases in the future.
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PMID:Role of interleukin-10 in atherogenesis and plaque stabilization. 1980 34


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