UNIPROT:P05231 - FACTA Search

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)

Markers of inflammation (eg, interleukin-6 [IL-6]), and endothelial perturbation (von Willebrand factor [VWF], circulating endothelial cells [CECs]) are altered in acute coronary syndromes (ACS). We hypothesized that CECs and IL-6 levels during the first 48 hours of ACS would predict 30-day and 1-year major cardiovascular end points (MACE). A total of 156 patients with ACS were included. Blood was drawn on admission (baseline) and 48 hours later for plasma VWF, IL-6 (both enzyme-linked immunosorbent assay [ELISA]), and CECs (CD146 immunomagnetic separation). CEC phenotyping was performed by indirect immunoperoxidase staining. At 30 days, 48 patients had a MACE, a predicted by baseline and 48-hour CECs and IL-6 levels, 48-hour VWF levels, and by the "admission-48 hour change" (Delta) in CECs, VWF, and IL-6 (all P = .002). On multivariate analysis, 48-hour CECs (P < .001) were the strongest predictor of MACE, followed by DeltaIL-6 (P = .01) and DeltaVWF (P = .048); 48-hour CECs were the only predictor of death (P = .007). At 1 year, 65 patients had MACE, predicted by 48-hour CECs and DeltaIL-6 levels (P < .001); age (P = .046) and 48-hour CECs (P < .001) were the only predictors of death. CECs stained 93% positive for endothelial nitric oxide synthase (eNOS) but were less than 1% positive for CD34, CD36, and CD45 and less than 3% for CD31. Like raised VWF, abnormal CECs and IL-6 levels during the first 48 hours of ACS were strongly associated with 30-day MACE. CECs at 48 hours were the only independent predictor of both death and MACE at 30 days and 1 year, indicating the crucial role of endothelial/vascular damage in ACS pathophysiology.
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PMID:Circulating endothelial cells, von Willebrand factor, interleukin-6, and prognosis in patients with acute coronary syndromes. 1537 79

Men with AS (ankylosing spondylitis) are at elevated risk for CHD (coronary heart disease) but information on risk factors is sparse. We compared a range of conventional and novel risk factors in men with AS in comparison with healthy controls and, in particular, determined the influence of systemic inflammation. Twenty-seven men with confirmed AS and 19 controls matched for age were recruited. None of the men was taking lipid-lowering therapy. Risk factors inclusive of plasma lipids, IL-6 (interleukin-6), CRP (C-reactive protein), vWF (von Willebrand factor), fibrin D-dimer, ICAM-1 (intercellular cell-adhesion molecule-1) and fibrinogen were measured, and blood pressure and BMI (body mass index) were determined by standard techniques. A high proportion (70%) of men with AS were smokers compared with 37% of controls (P = 0.024). The AS patients also had a higher BMI. In analyses adjusted for BMI and smoking, men with AS had significantly higher IL-6 and CRP (approx. 9- and 6-fold elevated respectively; P < 0.001), fibrinogen (P = 0.013) and vWF (P = 0.008). Total cholesterol and HDL-C (high-density lipoprotein cholesterol) were lower (P < 0.05 and P = 0.073 respectively) in AS and thus the ratio was not different. Pulse pressure was also significantly higher in AS (P = 0.007). Notably, adjustment for IL-6 and CRP levels rendered all case-control risk factor differences, except pulse pressure, non-significant. In accordance with this finding, IL-6 correlated positively (r = 0.74, P < 0.001) with fibrinogen, but negatively (r = -0.46, P = 0.016) with total cholesterol concentration. In conclusion, men with AS have perturbances in several CHD risk factors, which appear to be driven principally by systemic inflammatory mediators. Inflammation-driven atherogenesis potentially contributes to the excess CHD risk in AS.
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PMID:Cardiovascular risk parameters in men with ankylosing spondylitis in comparison with non-inflammatory control subjects: relevance of systemic inflammation. 1580 4

Inflammation and endothelial dysfunction play important roles in the pathophysiology of congestive heart failure (CHF), and the peptide bradykinin, generated during inflammation, may act as a defence mechanism by inducing vasodilation. Plasma bradykinin levels are increased in experimental heart failure but low in patients with advanced chronic CHF despite treatment with angiotensin-converting enzyme (ACE) inhibitors. It is not currently known how bradykinin behaves in less severe phases of CHF controlled by long-term ACE inhibitor treatment. We studied 10 male patients with clinically stable chronic CHF [New York Heart Association (NYHA) class II] on long-term ACE inhibitor treatment and 10 normal sex- and age-matched control subjects. High performance liquid chromatography/radioimmunoassay methods were used to evaluate plasma levels of bradykinin in relation to an array of parameters of endothelial function, coagulation and inflammation before and after stimuli of forearm arterial occlusion and physical exercise. CHF patients had higher levels of bradykinin (P = 0.008), activated factor XII (P = 0.049), interleukin-6 (P = 0.050) and tumour necrosis factor receptor II (sTNFRII) (P = 0.026) than controls. Arterial occlusion and exercise significantly increased bradykinin and von Willebrand factor levels in controls but not in CHF patients. The increase in brachial artery diameter after arterial occlusion was less in CHF patients (P = 0.036) and inversely related to baseline plasma levels of bradykinin (r = -0.855, P = 0.002) and sTNFRII (r = -0.780, P = 0.008). NYHA class II CHF patients during long-term treatment with ACE inhibitors have increased bradykinin levels and signs of inflammation. They are unable to respond adequately to stimuli of ischaemia and physical exercise which both require vasodilation.
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PMID:Impaired bradykinin response to ischaemia and exercise in patients with mild congestive heart failure during angiotensin-converting enzyme treatment. Relationships with endothelial function, coagulation and inflammation. 1598 53

Certain plant-derived compounds show selective estrogen receptor modulator (SERM) activity and may therefore be an alternative to the conventional hormone replacement therapy, which prevents osteoporosis but is also associated with an increased risk of breast and endometrial cancers. In the current study, we tested the effects of the hop-derived compounds 8-prenylnaringenin, 6-prenylnaringenin, xanthohumol and isoxanthohumol (1) to modulate markers of differentiation and gene expression in osteoblasts and (2) to regulate proliferation in MCF-7 breast cancer cells. Additionally, we analyzed the ER-binding affinities of these hop compounds as well as the ER-mediation of their effects. Bone-forming activity and ER-subtype specificity were investigated by measuring alkaline phosphatase (AP) activity in hFOB/ERalpha cells and regulation of gene transcription for AP, interleukin-6, pS2 and von Willebrand factor (VWF) in U-2 OS/ERalpha and U-2 OS/ERbeta cells. Our results demonstrate that AP, pS2 and VWF mRNA levels are significantly increased by the compounds in an estrogen-like manner via both ERalpha and ERbeta, while IL-6 is down-regulated in U-2 OS/ERalpha cells. Consistently, AP enzymatic activity is up-regulated by all compounds in hFOB/ERalpha9 cells. Depending on their concentration, all compounds show proliferative effects in MCF-7 cells. Except for 8-PN the hop constituents display an ERbeta-preference. Reversal of estrogen-specific AP-induction in Ishikawa cells indicates an ER-regulated mechanism. Finally, the flavonoids display cytotoxic effects only at high concentrations (> or =10(-4)M). In summary, we have demonstrated for the first time that specific phytoestrogen compounds found in hop extracts exert estrogen-like activities on bone metabolism. Regarding a potential for use in osteoporosis-prevention therapy, the dosage of a phytoestrogen, which is taken, will play an important role concerning a desired in vivo profile.
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PMID:Regulation of osteoblastic phenotype and gene expression by hop-derived phytoestrogens. 1601 5

The objectives of the project were the following: (1) to establish a group of patients with a confirmed diagnosis of systemic sclerosis (Ssc), (2) to perform a detailed entrance examination of each patient, (3) to determine concentrations of potential activity markers, and (4) to make a comprehensive examination of each patient 1 year after inclusion into the study. A total of 49 patients were examined, 36 with a limited form of SSc, 9 with diffuse SSc, and 4 with other forms of SSc. We determined plasma or serum levels of the N-terminal propeptide of procollagen type III (NPIIIP), interleukin-6 (IL-6), soluble receptor for interleukin-2 (sIL-2r), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), von Willebrand factor antigen (vWFAg), and big endothelin-1 (BET-1) using commercial kits, and urinary excretion of pyridinoline (PYR) and deoxypyridinoline (D-PYR) using high-performance liquid chromatography. Correlations of these markers with selected clinical data were calculated. The mean levels of all potential activity markers were increased compared with normal values, but differences were not significant. The levels of NPIIIP, D-PYR, and IL-6 were normal. The measured values after 1 year did not differ from the entry values. At entry, NPIIIP concentrations correlated with the finger-to-palm distance, and D-PYR corresponded with findings on a simplified health assessment questionnaire (FQ). IL-6 levels correlated with the leukocyte count, sIL-2r with the FQ, and ET-1 with the diffuse lung capacity for carbon monoxide. In general, we found only a few clinical correlates of potential activity markers. Our data confirmed the correlations of collagen metabolism markers with skin involvement and FQ, as was reported previously. Larger studies in this field are needed.
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PMID:Clinical correlations of potential activity markers in systemic sclerosis. 1612 82

Systemic factors and blood flow velocity related to atherosclerosis have been examined mainly separately or by in vitro studies. The aim of our study was to investigate the association between local coronary blood flow (corrected TIMI frame count, CTFC) and systemic atherosclerosis-related inflammatory parameters such as soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (Il-6), high sensitivity C-reactive protein (hsCRP) and von Willebrand factor (vWF) in humans. We enrolled the following groups of ischemic heart disease (IHD) patients: patients with coronary stenosis and stable (CAD, n = 96) or unstable angina (ACS, n = 27), patients with documented myocardial ischemia and normal coronary angiogram (NEG, n = 68). Patient groups showed only marginal differences in CTFC or sICAM-1 levels. In contrast, when IHD patients were studied individually, general positive correlation was found between CTFC and sICAM-1 level (r = 0.33; in NEG r = 0.25; in CAD r = 0.37; in ACS r = 0.61), being the strongest in ACS. The relation was independent from age, gender, BMI, smoking, hypertension, diabetes, previous myocardial infarction, family history of IHD, medication, hsCRP, IL-6 and vWF levels. (odds ratio, OR = 6.4; CI 95%: 2.43-16.84; p < 0.05). Nevertheless, correlation between CTFC and IL-6, hsCRP, vWF levels was not found. These results indicate inverse correlation between coronary blood flow and adhesion molecule production independently from conventional cardiovascular risk factors and inflammatory markers.
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PMID:Inverse correlation between coronary blood flow velocity and sICAM-1 level observed in ischemic heart disease patients. 1629 92

The interplay between inflammatory and hemostatic mechanisms may play a crucial role in the development and progression of atherosclerosis. The authors evaluated the separate and joint associations of hemostatic and inflammatory variables on peripheral atherosclerotic progression in the Edinburgh Artery Study, a population cohort study of 1,592 men and women aged 55-74 years that started in 1987. Levels of fibrinogen, fibrin D-dimer, von Willebrand factor, tissue plasminogen activator antigen, factor VII, prothrombin fragment 1 + 2, urinary fibrinopeptide A, C-reactive protein, and interleukin-6 were measured at baseline. Arm and ankle blood pressures were measured, and atherosclerotic progression was assessed by computing ankle brachial index (ABI) at baseline (1,582 participants) and after 12 years of follow-up (813 participants). Fibrinogen (p = 0.05) and D-dimer (p < or = 0.05) were significantly associated with ABI change independently of baseline ABI and cardiovascular disease risk factors. However, these associations were no longer significant when analyses were adjusted for either C-reactive protein or interleukin-6. Moreover, subjects with higher levels of both D-dimer and interleukin-6 at baseline had the greatest ABI decline. In conclusion, fibrinogen and D-dimer, but not other hemostatic factors, were associated with progressive peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation.
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PMID:Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis: the Edinburgh Artery Study. 1635 7

Risk stratification at presentation with acute coronary syndromes (ACS) on the basis of the TIMI risk score for unstable angina and non-ST-elevation myocardial infarction (UAP/NSTEMI) identifies patients at high risk of recurrent cardiac events and those who benefit from more aggressive treatment strategy. We hypothesised the following: (a) that a high TIMI risk score brings a greater degree of acute changes in endothelial damage/dysfunction (circulating endothelial cells [CECs], von Willebrand factor [vWf]), inflammation (interleukin-6, IL-6) and blood thrombogenicity (plasma tissue factor, TF); and (b) that these indices are higher in those with high TIMI risk score who experienced recurrent cardiac event at day 14 and day 30. TIMI risk scores were determined at admission and 48 hours later in 88 ACS patients (60 male, age 67+/-12 yrs) with UAP or NSTEMI. CECs, IL-6 and TF levels were measured at both time points and the acute change (delta) calculated. Patients were split into high (score > or =4) or low (<4) TIMI score groups. The composite end point of death, myocardial infarction, and refractory angina requiring revascularisation following 14 and 30 days' follow-up was ascertained. Fifty-eight patients with high TIMI risk score (mean 4.7) had significantly higher baseline and 48 h CEC, vWf, IL-6,TF and deltaTF levels, compared to low TIMI risk score (mean 2.4) patients (all p<0.05). Multivariate Cox regression analysis adjusted for clinical variables and TIMI risk score expressed as either continuous or categorical variable identified baseline CECs and deltavWf levels (both p< or =0.01) as independent predictors of subsequent cardiac events at both 14 days and 30 days. TIMI risk score for UA/NSTEMI identifies those patients with more profound vascular insult, inflammation and thrombogenicity that, in the 'high risk' patient group, predicts short-term outcomes, although vascular damage was the more sensitive predictor. These indices may further refine global risk stratification for short-term adverse cardiac events in these patients.
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PMID:Plasma markers of endothelial damage/dysfunction, inflammation and thrombogenesis in relation to TIMI risk stratification in acute coronary syndromes. 1636 52

ADAMTS13, a reprolysin-like metalloprotease, limits platelet-rich thrombus formation in the small arteries by cleaving von Willebrand factor (vWF) at the Tyr1605-Met1606 peptide bond. Deficiency of plasma ADAMTS13 activity, due to either an inherited or an acquired etiology, may lead to a potentially lethal syndrome, thrombotic thrombocytopenic purpura (TTP). Molecular cloning and characterization of the ADAMTS13 gene have provided further insight into the structure-function relationships, biosynthesis, and regulation of the ADAMTS13 protease, in addition to understanding the pathogenesis of TTP and perhaps other thrombotic disorders. ADAMTS13 consists of a short propeptide, a typical reprolysin-like metalloprotease domain, followed by a disintegrin-like domain, first thrombospondin type 1 (TSP1) repeat, Cys-rich domain, and spacer domain. The carboxyl terminus of ADAMTS13 has seven more TSP1 repeats and two CUB domains. ADAMTS13 is synthesized mainly in hepatic stellate cells, but also in vascular endothelial cells. Recognition and cleavage of vWF require the proximal carboxyl terminal domains, but not the middle and distal carboxyl terminal domains. Cleavage of vWF appears to be modulated by shear force, binding to platelet or platelet glycoprotein-1balpha, heparin, inflammatory cytokine (interleukin-6), and chloride ion. At the site of thrombus formation, the ADAMTS13 may be inactivated by thrombin, plasmin, and factor Xa. Having a sensitive and specific assay for ADAMTS13 activity is not only critical to understand the basic biology of ADAMTS13 protease, but also to facilitate a more timely and accurate clinical diagnosis of TTP, and to initiate potentially life-saving plasma exchange therapy. Although many assays have been developed and tested for clinical applications, the fluorescent resonance energy transfer-vWF73 assay appears to be the simplest and most promising assay to date.
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PMID:Molecular biology of ADAMTS13 and diagnostic utility of ADAMTS13 proteolytic activity and inhibitor assays. 1638 17

We studied the state of ultra-large von Willebrand factor (ULVWF) proteolysis in 21 pediatric patients with severe sepsis and found that the overall group of patients had moderately reduced ADAMTS-13 activity, but 31% had severe enzymatic deficiency. The severe deficiency correlated with greater adhesion activity of von Willebrand factor, severity of thrombocytopenia and plasma levels of interleukin-6. It also correlated clinically with severity of illness and organ dysfunction. These results suggest that ULVWF proteolysis is insufficient in septic patients and severely deficient in a subgroup of patients. The deficiency may contribute to the development of thrombocytopenia and ischemic organ failure associated with sepsis.
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PMID:Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis. 1722 45

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