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)

Patients with heterozygous familial hypercholesterolemia (hFH) are at very high risk for premature coronary heart disease. In the last decade, treatment with statins has reduced cardiovascular mortality in these patients. The aim of this study was to analyze arterial endothelial function assessed as flow-mediated dilatation (FMD) and soluble E-selectin (sE-selectin) levels in patients with hFH under a long-term lipid-lowering treatment. Twenty-five patients who completed the study received a dose of simvastatin to achieve a treatment goal of at least 30% reduction in serum low-density lipoprotein (LDL)-cholesterol (LDL-C) for 52 weeks. Functional and biochemical measurements were taken at entry, and at week 12 and 52 of treatment. FMD was measured by vascular ultrasound of the brachial artery. sE-selectin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 were determined by enzyme linked immunosorbent assay (ELISA). LDL-C levels were significantly reduced by treatment at week 12 and maintained at week 52 (reduction vs. baseline, 44+/-12 and 43+/-11%, respectively, P<0.0001). A significant improvement in endothelial function, measured as FMD (baseline, 4.7+/-6.2%; 12 weeks, 12.3+/-5.9%; 52 weeks, 9.7+/-4.7%; P<0.005) and a reduction in sE-selectin levels (baseline, 16.2+/-3.4 ng/ml; 12 weeks, 11.0+/-3.2 ng/ml; 52 weeks, 12.3+/-4.2 ng/ml; P<0.01) were observed. Endothelial-independent relaxation induced by nitroglycerin was not modified during the study. Our results indicate that a long-term treatment with simvastatin produced a sustained beneficial effect in endothelial function in hFH patients.
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PMID:Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin. 1147 43

Inflammation contributes to atherosclerosis, but assessment in humans is largely restricted to measurement of markers in blood. We determined whether MRI properties of large arteries were associated with markers of inflammation in serum. Double inversion recovery, fast spin-echo images of the common carotid arteries and infrarenal aorta were obtained at 1.5 T both before and after gadolinium-DTPA (0.1 mmol/kg) in 52 subjects > or =40 years of age, 17 of whom had no risk factors for atherosclerosis and thus served as controls. Twenty-two study participants had increases in wall thickness (14), T2-weighted signal intensity (11), and/or contrast enhancement values (7) that were >2 standard deviations (SDs) from control group mean values. Ten subjects in this group had evidence of focal plaques in the carotids (5) and/or aorta (6). Compared with the remaining 30 subjects, these 22 had significantly higher levels of interleukin-6 (3.53 +/- 2.46 vs. 1.97 +/- 1.37 pg/mL, P = 0.004), C-reactive protein (0.56 +/- 0.98 vs. 0.30 +/- 0.52 mg/dL, P = 0.019), vascular cell adhesion molecule-1 (572 +/- 153 vs. 471 +/- 130 ng/mL, P = 0.012), and intercellular adhesion molecule-1 (244 +/- 80 vs. 202 +/- 45 ng/mL, P = 0.015), and nonsignificant differences in levels of E-selectin (46.1 +/- 18.9 vs. 42.3 +/- 11.3 ng/mL, P = 0.369). Thus, MRI characteristics of the aorta and carotid arteries were associated with elevated serum markers of inflammation, frequently in the absence of definite atheroma. MRI of large arteries may provide a new approach to investigate the contribution of inflammation to atherogenesis.
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PMID:Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans. 1174 26

We compared six inflammatory mediators (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumour necrosis factor receptors (p55 and p75) and soluble adhesion molecules (ICAM-1, E-selectin)) as early diagnostic tests for neonatal sepsis, and studied the possible benefit of combining parameters. Blood samples were obtained from 166 consecutively admitted neonates, who were suspected to suffer from infection within the first week of life. Neonates were retrospectively classified as infected (sepsis, clinical sepsis or pneumonia), possibly infected, or non-infected. Twenty-four infected neonates had higher serum levels of all six mediators (all P < 0.05), and 18 possibly infected neonates had higher levels of CRP, IL-6, ICAM-1 and E-selectin (all P < 0.05), than neonates without infection (n = 124). Receiver operator characteristic plots showed that CRP was the single best diagnostic test. Multiple logistic regression modelling, including various combinations of two to six mediators, consistently showed that IL-6, in addition to CRP, predicted sepsis. With infected and possibly infected neonates as the reference standard, a combined test of CRP > or = 10 mg/l and/or IL-6 > or = 20 pg/ml had a sensitivity of 85%, specificity of 62%, and negative likelihood ratio of 0.24. Using infected neonates as reference standard alone, and including possibly infected as controls, sensitivity increased to 96%, whereas specificity decreased to 58%; a negative test result (CRP < 10 mg/l and IL-6 < 20 pg/ml) ruled out sepsis with high certainty (likelihood ratio = 0.07). CRP performed best as a diagnostic test for neonatal sepsis. Diagnostic accuracy was further improved by combining CRP and IL-6, whereas the other parameters (p55, p75, ICAM-1 and E-selectin) added no further diagnostic information.
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PMID:Early diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6, soluble tumour necrosis factor receptors and soluble adhesion molecules. 1175 Jan 94

Greatly increasing the amounts of flaxseed oil [rich in alpha-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo oil (an 80:20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO. Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in response to bacterial lipopolysaccharide; or plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin (23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty acids, a moderate increase in consumption of long-chain n-6 or n-3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment. Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n-3 fatty acids.
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PMID:Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. 1179 50

Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor alpha (TNFalpha). interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all <0.001). In multivariate analysis sVCAM-1 was predicted by age (p=0.015), sICAM-1 by smoking (p<0.001) and total cholesterol (p=0.026), E-selectin by body mass index (BMI) (p=0.004) and P-selectin by male gender (p=0.015). TNFalpha significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNFalpha, but not IL-6, plays a major role in the regulation of sCAM levels in vivo.
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PMID:Increased levels of markers of vascular inflammation in patients with coronary heart disease. 1200 14

It is possible that in fetal growth restriction without pre-eclampsia endothelial cell activation does not occur. This might be either because there is no release of 'factor X' or because of maternal resistance to its effects. To test this hypothesis, we took blood samples from 26 women with pre-eclampsia (without fetal growth restriction), 13 women with fetal growth restriction (without pre-eclampsia) and 24 normal pregnant controls, and measured the circulating levels of three markers of endothelial cell activation (soluble VCAM, ICAM and E-selectin) and three cytokines [tumour necrosis factor-a (TNF-alpha), interleukin-6 (IL-6) and -8 (IL-8)]. The levels of the markers of endothelial cell activation were raised in both pre-eclampsia and fetal growth restriction pregnancies compared with controls; however, the levels of TNF-alpha, IL-6 and IL-8 were significantly raised in pregnancies complicated by pre-eclampsia, but not in fetal growth restriction, compared with controls. These data show that endothelial cell activation is common to both pre-eclampsia and fetal growth restriction, but that the circulating levels of cytokines are elevated only in pre-eclampsia. Thus, it seems likely that endothelial cell activation is a consequence of a failure of trophoblast invasion and that a further step is required, possibly involving cytokine release, for the expression of the full clinical picture of pre-eclampsia.
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PMID:Does endothelial cell activation occur with intrauterine growth restriction? 1213 23

There is a lack of data on circulating levels of cell-adhesion molecules in relation to subclinical atherosclerosis measured in both the carotid and femoral arteries in humans. The aim of the present study was to investigate the relationship between clinically silent atherosclerosis and cell-adhesion molecules, and to explore the relationship between these molecules, C-reactive protein and the inflammatory cytokines interleukin-6, tumour necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptor p55 and soluble TNF-alpha receptor p75. The study group (n=391) consisted of clinically healthy 58-year-old men recruited from the general population. The results showed a positive trend between levels of soluble intercellular cell-adhesion molecule 1 (sICAM-1) and plaque occurrence in the carotid and femoral arteries (P=0.008), and also a univariate correlation between sICAM-1 levels and the composite variable of carotid and femoral intima-media thickness (P<0.001). When adjusted for other risk factors, the relationship between sICAM-1 and intima-media thickness no longer reached statistical significance. The level of sICAM-1 was associated with those of the pro-inflammatory cytokine TNF-alpha, its two soluble receptors, and also interleukin-6 and C-reactive protein. Levels of soluble E-selectin and vascular cell-adhesion molecule 1 (VCAM-1) showed weak or no association with subclinical atherosclerosis and inflammatory variables. Thus, in clinically healthy middle-aged men, levels of sICAM-1, but not of soluble VCAM-1 or E-selectin, were associated with both subclinical atherosclerosis and inflammatory variables.
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PMID:Circulating ICAM-1 (intercellular cell-adhesion molecule 1) is associated with early stages of atherosclerosis development and with inflammatory cytokines in healthy 58-year-old men: the Atherosclerosis and Insulin Resistance (AIR) study. 1214 2

Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interleukin-6 and interleukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11b, CD64), and antiinflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.
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PMID:Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. 1258 9

Hemiconvulsions-hemiplegia (HH) syndrome is an acquired condition in which hemiplegia develops after a preceding febrile unilateral status epilepticus in a previously healthy child. Although viral encephalitis or vascular diseases may be the underlying etiology, the pathogenesis remains unknown in the majority of cases. We measured both plasma and cerebrospinal fluid cytokine levels in a girl with HH syndrome, and found elevated plasma concentrations of soluble interleukin-2 receptor and tumor necrosis factor-alpha, and a slightly increased plasma level of interleukin-6. Furthermore, she had a high serum concentration of soluble E-selectin, which is a marker of inflammatory endothelial activation. These findings suggest that proinflammatory cytokine-induced cerebrovascular endothelial injury could play a role in the pathogenesis of HH syndrome.
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PMID:Hypercytokinemia in hemiconvulsions-hemiplegia syndrome associated with dual infection with varicella zoster and Epstein-Barr viruses. 1253 69

This study determined the concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1) and soluble E-selectin (sE-selectin) in cerebrospinal fluid (CSF) and serum from 15 children with influenza virus-associated encephalopathy to determine the role of cytokines in the pathogenesis. Cytokines and sTNFR1 were measured by enzyme-linked immunosorbent assay. The CSF IL-6, TNF-alpha and sTNFR1 concentrations were elevated in 9, 4 and 4 of 12 children, respectively. The serum concentrations of IL-6, TNF-alpha, sTNFR1 and sE-selectin were elevated in 10, 2, 5 and 7 of 13 children, respectively. Four children with elevated TNF-alpha and sTNFR1 levels in the CSF had neurological sequelae. The results suggested that cytokines not only in serum but also in CSF play a pivotal role in influenza virus-associated encephalopathy, and that the CSF TNF-alpha and sTNFR1 levels may be important for predicting neurological sequelae.
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PMID:Cerebrospinal fluid and serum levels of cytokines and soluble tumor necrosis factor receptor in influenza virus-associated encephalopathy. 1268 86


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