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)

Elevated levels of both fibrinogen and cholesterol are risk factors in coronary artery disease. Previously we reported a metabolic link between fibrinogen and lipid metabolism in that HepG2 cells that were programmed by transfection of Bbeta-fibrinogen cDNA to overexpress fibrinogen exhibited increased synthesis of cholesterol and increased secretion of apolipoprotein B. In this study we demonstrate that oxysterols, which participate in maintaining cholesterol homeostasis, also down regulate fibrinogen expression. Treatment of HepG2 cells with 25-hydroxycholesterol lowered fibrinogen Aalpha, Bbeta and gamma mRNA levels and inhibited fibrinogen synthesis and secretion but had no effect on alpha1 -antitrypsin which, like fibrinogen, is an acute-phase protein. The inhibition of fibrinogen synthesis by oxysterols was maintained in interleukin-6 treated cells. Other oxysterols, that inhibit cholesterol synthesis by a feedback mechanism, also diminished fibrinogen expression in HepG2, rat H-4-II-E hepatoma cells and in primary human hepatocytes. Overexpression of SREBP-1 and SREBP-2 by transfection of HepG2 cells, or treatment with a synthetic LXRalpha agonist, which affect cholesterol metabolism, did not affect fibrinogen expression. We conclude that fibrinogen and cholesterol may share a novel common regulatory pathway.
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PMID:Oxysterols suppress constitutive fibrinogen expression. 1287 24

Axillary lymph node involvement in breast cancer is a marker of recurrence risk. Despite aggressive adjuvant therapy, recurrence in patients with four or more involved lymph nodes approaches 50% at 5 years from diagnosis. Markers that can distinguish those likely to relapse from those likely to be cured are needed to tailor therapy and provide accurate prognostic information to patients. Although most work in this area has focused on tumor characteristics, we hypothesized that the host environment might also play a role in determining risk of relapse. We hypothesized that host inflammatory response, mediated in part by production of interleukin-6 (IL-6), might play a role in the elimination of microscopic residual tumor. Polymorphisms in the IL-6 promoter region appear to modulate serum levels of the cytokine via regulation of gene transcription. A single nucleotide polymorphism involving substitution of cytosine for guanine at position -174 has been associated with reduced transcription and improved outcome in a variety of nonmalignant diseases, including coronary artery disease and several autoimmune conditions. Tumor necrosis factor (TNF) alpha is a proinflammatory cytokine that also plays a role in regulating IL-6 transcription. We hypothesized that polymorphisms in IL-6 (-174 G>C) or TNF-alpha (G-238 or G-308) might be associated with prognosis in a subset of patients with high-risk breast cancer. Genotyping was performed on DNA from stored stem cells in 80 breast cancer patients diagnosed with at least four positive axillary lymph nodes at diagnosis who underwent anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem cell rescue. Cox proportional hazards models were used to estimate the effect of genotype and other known prognostic factors on disease-free and overall survival (DFS and OS, respectively). The presence of at least one C allele in the IL-6 promoter at position -174 was significantly associated with both DFS and OS compared with G/G homozygotes. After adjustment for estrogen receptor (ER) status, number of involved lymph nodes, and tumor size, those patients carrying the G/G genotype had a 2.1-fold increase in the rate of failure and a 2.6-fold increase in the rate of death compared with carriers of any C allele at a mean follow-up of 55 months. ER status modulated the effect of IL-6 polymorphism: both DFS and OS were most favorable in patients who were carriers of any C-allele (G/C or C/C) and had ER-positive tumors. The presence of either G/G genotype or an ER-negative tumor increased the hazard of failure [hazard ratio (HR), 2.6 and 3.2, respectively] and death (HR, 2.0 and 2.2, respectively). The combination of both G/G genotype and ER-negative tumor resulted in an additional increase in the hazard of failure (HR, 5.4; four-group comparison, P = 0.003) and death (HR, 6.2; four-group comparison, P = 0.001). TNF-alpha -308 and -238 polymorphisms were not associated with variation in DFS or OS in this cohort. The IL-6-174 promoter polymorphism is associated with clinical outcome in this cohort of node-positive breast cancer patients who received high-dose adjuvant therapy. IL-6 genotype modulated the effect of ER status on outcome. These results support the hypothesis that IL-6 may play an important role in the control of micrometastatic disease in breast cancer. Additional studies are needed to confirm these results and elucidate the mechanisms responsible for these differences.
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PMID:Interleukin-6 -174G-->C polymorphism is associated with improved outcome in high-risk breast cancer. 1463 38

There is evidence that moderate consumption of red wine with its high content of polyphenolic antioxidants may be more protective than white wine against development of coronary artery disease (CAD). The aim of this study was to compare the acute effects of ingestion of red wine and white wine on markers of inflammation in men with CAD. Thirteen men with angiographically-proven CAD were studied in a cross-over trial. The men consumed 4 mL/kg (2 to 3 glasses) red wine and white wine in random order during a light meal and with at least a week between interventions. Later, the men also consumed an isoenergetic nonalcoholic beverage (control) in the same study protocol. Venous blood was taken at baseline, 1 hour, and 6 hours after the drinks. Plasma interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), blood alcohol, plasma lipids, and plasma polyphenols were measured. Mean +/- SD blood alcohol was 6.5 +/- 2.2 mmol/L and 6.9 +/- 1.1 mmol/L at 1 hour and returned to baseline at 6 hours after intake of red wine and white wine, respectively. Plasma IL-6 concentration increased significantly (P =.01) during 6 hours after ingestion of red wine (56%) and white wine (63%). The increase in plasma IL-6 concentration after ingestion of wine was significantly higher (P =.045) compared with the corresponding increase (11%) following intake of the nonalcoholic beverage. Plasma IL-6 levels at 6 hours (r =.631, P =.02) were correlated significantly with plasma alcohol levels at 1 hour after ingestion of red wine. These data suggest that moderate wine intake may acutely increase plasma levels of IL-6 in men with CAD. It is possible that this increase in plasma IL-6 is a response to alcohol-induced oxidative stress in the liver.
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PMID:Acute effect of drinking red and white wines on circulating levels of inflammation-sensitive molecules in men with coronary artery disease. 1501 43

Inflammation and the recruitment of monocytes into the artery wall are thought to be important aspects in the initiation and progression of atherosclerosis. The present study was designed to examine the effects of a rigorous diet and exercise intervention on plasma lipids and inflammatory and circulating adhesion molecules. Twenty postmenopausal women at risk for coronary artery disease (CAD) were placed on a high-fiber, low-fat diet, where food was provided ad libitum and daily aerobic exercise, primarily walking, was performed. In each subject, pre- and post-intervention fasting blood was drawn for serum lipid, insulin, glucose, C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and both soluble (s) intracellular and vascular adhesion molecule (sICAM-1 and sVCAM-1) were measured. After 2 weeks, significant reductions in body mass index (BMI) (P <.001), glucose (P <.05), insulin (P <.01), all serum lipids, and total cholesterol (total-C):high-density lipoprotein-cholesterol (HDL-C) (P <.01). Reductions in homeostasis model assessment for insulin resistance (HOMA-IR) (P <.01), CRP (P <.01), SAA (P <.01) and sICAM-1 (P <.05) were noted, as well as an increase in the quantitative insulin sensitivity check index (P <.05). Reductions were also noted in 5 women not using hormone replacement therapy (HRT). No significant reductions were found in IL-6 or sVCAM-1 in response to the intervention. Overall, this intervention resulted in improved metabolic and lipid profiles, reduced inflammatory, and cell adhesion molecules in postmenopausal women in the absence of caloric restriction. The rapid improvements may reduce the risk of acute myocardial infarction (MI), and if sustained, these changes may mitigate the risk for atherosclerosis progression and its clinical consequences.
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PMID:Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease. 1501 51

Coronary artery disease (CAD) is more prevalent in people from a low socioeconomic background, and low socioeconomic status (SES) is associated with an increased exposure to psychological stress. The pro-inflammatory cytokine interleukin-6 (IL-6) plays a central role in CAD development. IL-6 is responsive to psychological stress and could potentially mediate the effect of psychosocial factors on CAD risk. Accordingly, we predicted that people of low SES would have greater and/or more sustained IL-6 responses to acute psychological stress. Based on previous findings, we also predicted that these people would have delayed post-stress cardiovascular recovery. Thirty-eight male civil servants were tested, with participants divided into high and low SES groups according to employment grade. There were no differences between the groups at baseline. However there were significant differences in IL-6 and heart rate responses to stress. Stress induced increases in plasma IL-6 in all participants. However, in the low SES group, IL-6 continued to increase between 75 min and 2h post-stress, whereas IL-6 levels stabilised at 75 min in the high SES group. Heart rate increased to the same extent following stress in both groups, however by 2h post-stress, it had returned to baseline in 75% of the high SES group compared with only 38.1% of the low SES group. These results suggest that low SES people are less able to adapt to stress than their high SES counterparts. Prolonged stress-induced increases in IL-6 in low SES groups represents a novel mechanism potentially linking socioeconomic position and heart disease.
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PMID:Socioeconomic status and stress-induced increases in interleukin-6. 1505 Jun 55

Rheumatoid arthritis (RA) is a systemic disease that is associated with increased mortality and morbidity. Prognosis depends on disease severity and response to treatment. Those patients whose diseases are refractory to treatment with disease-modifying antirheumatic drugs (DMARDs) and have persistent inflammation have reduced survival similar to patients with triple-vessel coronary artery disease and Hodgkin's lymphoma. Although DMARDs reduce inflammation and improve symptoms, they do not improve long-term prognosis. Chronic synovial inflammation results in damage to the articular cartilage and adjacent bone. Consequently,after 10 years of disease most patients develop significant disability due to joint damage. Interleukin-6 (IL-6) is a key mediator of inflammation in RA. Inhibition of IL-6 reduces synovitis and improves symptoms. Therapies targeting IL-6 are promising new treatments for RA.
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PMID:Clinical experience with inhibition of interleukin-6. 1517 49

Several evidences, ranging from in vitro experiments, pathologic analysis and epidemiologic studies, show that atherosclerosis is intrinsically an inflammatory disease. The plasma concentrations of interleukin-6 (IL-6) and its hepatic by-product, C-Reactive Protein (CRP), appear to reflect the intensity of occult plaque inflammation and by inference may determine the vulnerability of plaque rupture. The monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in initiating coronary artery disease by recruiting monocytes/macrophages to the vessel wall. This leads to the formation of atherosclerotic lesions and also increases the vulnerability of the plaque. Indeed, circulating IL-6 and MCP-1 levels are elevated in patients with acute myocardial infarction, and also in patients with unstable angina, but not in those with stable angina. The plasma IL-6 and MCP-1 concentrations are also increased after percutaneous coronary intervention (PCI), and late restenosis is correlated with an increase in IL-6 or MCP-1 concentrations after the procedure. This finding suggests that the expression of IL-6 and MCP-1 may not only be related to the instability of atheromatous plaques, but also to the formation of restenotic lesions after PCI. The development of drugs specifically targeted against IL-6 and MCP-1 may be useful in the prevention of plaque formation, myocardial infarction and restenosis.
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PMID:Inflammation and coronary artery disease. 1532 Aug 54

The effects of cerivastatin and fenofibrate on proteins involved in haemostasis and on markers of inflammation were investigated in otherwise healthy middle-aged males with combined hyperlipidemia. Besides classical risk factors, other so-called novel risk factors for coronary artery disease are seen to be playing an increasingly important role in the development and progression of atherosclerosis. Thirty-eight males, aged 49 +/-5 years were randomised to 12 weeks treatment either with cerivastatin at a daily dose of 0.2 mg to 0.4 mg to achieve the LDL cholesterol goal of <3.0 mM, or with fenofibrate 250 mg daily. Fasting serum lipids, homocysteine, total and free tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) antigen and activity, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured. No change in homocysteine level was observed in the cerivastatin group, while after fenofibrate administration it increased (p <0.0001). Total TFPI decreased significantly after cerivastatin (p = 0.002), but not after fenofibrate. Free TFPI did not decrease after either drug. Neither drug affected (t-PA) antigen and activity, while fenofibrate increased PAI-1 antigen (p <0.05) and activity (p <0.05). Cerivastatin decreased serum CRP values by 49.5% (p = 0.001), and fenofibrate by 29.8% (p = 0.03). The decreases of CRP in the two groups differed significantly (p = 0.04). IL-6 levels decreased significantly in the fenofibrate group (39%; p <0.0001), but not in the cerivastatin group (15%; p = 0.24) No significant decreases were observed for TNF-alpha. Cerivastatin had neutral effects on fibrinolysis, homocysteine or coagulation. On the other hand, fenofibrate increased PAI-1 antigen and activity and homocysteine, and did not affect coagulation. Both cerivastatin and fenofibrate reduced CRP levels, the decrease being significantly greater after cerivastatin. Fenofibrate also significantly decreased IL-6.
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PMID:Statin and fibrate treatment of combined hyperlipidemia: the effects on some novel risk factors. 1554 43

Inflammation within coronary plaques may cause an acute coronary syndrome by promoting rupture and erosion. It was the aim of this study to examine whether markers of inflammation derive from a cardiac or extracardiac source and how their levels develop over time. Blood samples were taken from patients with acute coronary syndromes (ACS) with proven atherosclerotic lesion(s) of the left coronary artery (n=13) and from control patients without coronary artery disease (n=13). Blood was taken from the femoral vein and the coronary sinus vein before and after coronary angioplasty (day 0) and on days 1 and 120. Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1 ra) and soluble CD40 ligand (sCD40L) were higher in ACS patients as compared to controls and remained elevated up to day 120. In the long-term time course these markers of inflammation and plaque remodeling slightly decreased in ACS patients. There were no statistically significant differences detectable in the levels of TNF-alpha, IL-6, IL-1 beta, IL-10, IL-1 ra, sCD40L and monocyte chemoattractant protein-1 (MCP-1) in the blood of ACS patients taken from a cardiac source as compared to an extracardiac source (coronary sinus vs. femoral vein). This study demonstrates the importance of a systemic inflammatory condition in patients with ACS, in whom markers of inflammation are increased as compared to controls. During long-term follow-up the pro-inflammatory activity remains elevated in ACS patients, supporting the concept of a systemic rather than a local vascular inflammation contributing to the development of atherosclerosis.
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PMID:Time course of systemic markers of inflammation in patients presenting with acute coronary syndromes. 1555 72

Inflammation plays a pivotal role in atherosclerosis and coronary heart disease. Inflammatory processes of the coronary arterial wall are involved in plaque formation, progression and, finally, plaque instability consecutively leading to the clinical manifestations of stable coronary artery disease or acute coronary syndromes (unstable angina, non-ST elevation and ST elevation myocardial infarction). Acute coronary syndromes result from plaque rupture or erosion leading to local thrombus formation with consecutive necrosis of myocytes due to ischemia, which is associated with widespread and diffuse pancoronary and panmyocardial inflammation. Accordingly, markers of myocardial necrosis (e. g., cardiac troponins) do have crucial diagnostic and prognostic value. In case of troponin-negative acute coronary syndromes, however, markers of inflammation emerged as potentially useful tools for risk stratification. C-reactive protein has been shown to serve as a powerful predictor of future cardiovascular events following acute coronary syndromes, even if troponins are not (yet) positive. Moreover, a variety of pro- (soluble CD40 ligand, placental growth factor, interleukin-6, pregnancy-associated plasma protein A, myeloperoxidase, monocyte chemoattractant protein-1) and anti-inflammatory markers (interleukin-10, activin A) have been suggested to provide relevant prognostic information in patients with acute coronary syndrome. However, the clinical utility of these novel markers has not been established so far.
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PMID:[Acute coronary syndrome and inflammation. Biomarkers for diagnostics and risk stratification]. 1559 73


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