UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in circulating levels of catecholamines, cortisol, glucose, interleukin-6 and C-reactive protein and in the leucocyte count were investigated for 7 days after surgery in 158 patients undergoing hip or knee arthroplasty. We compared the responses to the two operations, and also examined the effects of pathology (osteoarthritis and rheumatoid arthritis) on the changes associated with knee arthroplasty. Exploratory factor analysis was applied to the data to identify the variables and sampling times that could be used in future to provide a concise description of the response. Patients undergoing knee arthroplasty showed significantly greater changes in noradrenaline, adrenaline and glucose levels, but not in cortisol levels, compared with those undergoing hip arthroplasty. Interleukin-6 and C-reactive protein concentrations were also significantly greater in knee patients than hip patients; however, when corrected for pathology, many of these differences were not significant. Minimal effects of pathology (chronic inflammation with rheumatoid arthritis) were found on the hormonal changes in knee patients. In particular, there was little evidence to support the inference from animal data that the hypothalamic-pituitary-adrenal axis is impaired. The expected increases in interleukin-6 and C-reactive protein concentrations were found in the rheumatoid arthritis patients. Exploratory factor analysis showed that the response could be separated into six components, accounting for 60% of the total variance, and identified the variables and sampling times indicative of each. In conclusion, there are differences in the hormonal, but not inflammatory, responses to hip and knee arthroplasty. Little evidence was found for an important effect of pathology on the changes associated with knee surgery. Factor analysis provided a useful summary of the data.
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PMID:Hip and knee arthroplasty: a comparison and the endocrine, metabolic and inflammatory responses. 1060 Jun 61

Growing (35 kg body weight) and finishing (85 kg body weight) swine challenged with endotoxin (Escherichia coli O55:B5) at a dose of either 2 or 20 microg/kg produced tumor necrosis factor (TNF)alpha in a dose-response relationship as measured by bioassay. Peak TNFalpha plasma levels were observed 1-2 hr post-challenge, returning to basal values 4 hr post-challenge. However, both an enzyme-linked immunosorbent assay specific for swine TNFalpha and total human TNFalpha demonstrated no dose-response relationship; peak plasma levels of immunoreactive TNFalpha were also observed 1-2 hr post-challenge. Maximal plasma interleukin-6 levels occurred 1-2 hr post-challenge and remained elevated through 8 hr post-challenge; there was no effect of lipopolysaccharide dose or metabolic status. Although the metabolic status of the animals also affected glucose levels, with growing animals exhibiting greater sensitivity compared with finishing animals, endotoxin-induced decreases in blood glucose levels were primarily dose-dependent. In contrast, changes in plasma urea nitrogen and free fatty acid (FFA) levels were strictly related to the metabolic status. Urea nitrogen levels were unchanged in growing swine, whereas they were increased in finishing swine and remained elevated 24 hr post-challenge. FFA levels in growing and finishing swine increased 3-6 hr post-challenge. FFA levels returned to basal values for finishing swine 24 hr post challenge, but in growing swine remained elevated 24 hr post-challenge. Plasma aspartate transaminase levels were increased through 24 hr post-challenge; animals given a dose of 20 microg/kg exhibited the greatest increase. Similarly, swine challenged with a dose of 20 microg/kg also exhibited the greatest increase in levels of conjugated bilirubin; there was no effect on unconjugated (free) bilirubin. These results demonstrate that endotoxin challenge of swine result in a pattern of changes that are dependent on both the dose of endotoxin used and the metabolic status of the animal examined.
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PMID:Challenge differentially affects cytokine production and metabolic status of growing and finishing swine. 1062 26

Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-alpha and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMI-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (<0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.
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PMID:Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. 1072 86

Type 2 diabetes and the insulin resistance syndrome have been hypothesized to constitute manifestations of an ongoing acute-phase response. We aimed to study an interleukin-6 (IL-6) gene polymorphism in relation to insulin sensitivity (IL-6 is the main cytokine involved in an acute-phase response). Subjects homozygous for the C allele at position -174 of the IL-6 gene (SfaNI genotype), associated to lower plasma IL-6 levels, showed significantly lower integrated area under the curve of serum glucose concentrations (AUCglucose) after an oral glucose tolerance test, lower blood glycosylated hemoglobin, lower fasting insulin levels, lower total and differential white blood cell count (a putative marker of peripheral IL-6 action), and an increased insulin sensitivity index than carriers of the G allele, despite similar age and body composition. A gene dosage effect was especially remarkable for AUCglucose (6.4 vs. 9.3 vs. 9.7 mmol/l in C/C, C/G, and G/G individuals, respectively). The serum concentration of fully glycosylated cortisol binding globulin (another marker of IL-6 action), suggested by concanavalin A adsorption, was lower in C/C subjects than in G/G individuals (32.6+/-2.9 vs. 37.6+/-4.6 mg/l, P = 0.03). In summary, a polymorphism of the IL-6 gene influences the relationship among insulin sensitivity, postload glucose levels, and peripheral white blood cell count.
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PMID:Interleukin-6 gene polymorphism and insulin sensitivity. 1086 78

The neurotropism of Japanese encephalitis virus (EV) has not been well characterized. Astrocytes are parts of the blood-brain barrier, a major source of chemokines, and critical effectors of central inflammation. Thus, astrocytes might play some role as JEV travels from the peripheral to the CNS and/or the resultant encephalitis. Using rat cortical cultures, we found that JEV can cause cellular and/or functional changes in astrocytes as indicated by increased expression of interleukin-6 (IL-6), regulated by activation, normal T cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1), increased lactate release and glucose uptake, and attenuation of glutamate toxicity. These modulations occur needed by the cells for compensation and may affect neuron and/or astrocyte function.
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PMID:Astrocytic alteration induced by Japanese encephalitis virus infection. 1088 46

Reactive oxygen intermediates (ROIs) are important mediators of a variety of pathological processes, including inflammation and ischemia/reperfusion injury. Cytokines and chemokines are detected at mRNA level in human and animal ischemic brains. This suggests that hypoxia/reoxygenation may induce cytokine production through generation of ROIs. In this study, we investigated the cytokine induction and inhibition by antioxidants in rat cortical mixed glial cells exposed to in vitro ischemia-like insults (hypoxia plus glucose deprivation). The results showed that interleukin-6 (IL-6) mRNA and protein, but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta), were induced during hypoxia/hypoglycemia followed by reoxygenation in the mixed glial cells. The accumulation of IL-6 mRNA was induced as early as 15 min after hypoxia/hypoglycemia and its level was further increased after subsequent reoxygenation. Among the antioxidants studied, only resveratrol suppressed IL-6 gene expression and protein secretion in mixed glial cultures under hypoxia/hypoglycemia followed by reoxygenation. These findings suggest that resveratrol might be useful in treating ischemic-induced inflammatory processes in stroke.
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PMID:Resveratrol inhibits interleukin-6 production in cortical mixed glial cells under hypoxia/hypoglycemia followed by reoxygenation. 1110 30

GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months, with dose adjustments made according to serum insulin-like growth factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T(4), thyroid hormone binding index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval, 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be one of the mechanisms involved in the putative modulation of atherosclerosis and cardiovascular risk by GH replacement.
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PMID:Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: a randomized controlled trial. 1129 77

Adipocytes produce the inflammatory cytokine interleukin-6 (IL-6); however, it is not known whether these cells express the IL-6 receptor system, how the secretion of this cytokine is regulated, and whether it has a function within adipose tissue. Using cultured human breast adipocytes, we investigated the expression of IL-6 and its receptor system, the effects of IL-6 on main adipocyte functions, and the regulation of IL-6 secretion by catecholamines and glucocorticoids. In the culture system, immunohistochemistry demonstrated expression of IL-6 and its receptor system, consisting of the ligand-binding IL-6 receptor and the signal-transducing protein gp130, in mature adipocytes, but not in undifferentiated adipocyte precursor cells. In freshly isolated adipocytes, RT-PCR detected messenger ribonucleic acids encoding the above proteins. Chronic incubation of adipocytes with 1 nmol/L IL-6 during adipose differentiation reduced glycero-3-phosphate dehydrogenase (GPDH) activity, a marker of adipocyte differentiation, and triglyceride synthesis to 67 +/- 9% of the basal level (mean +/- SEM; P < 0.05) only on day 21. Incubation of differentiated adipocytes with 10 nmol/L IL-6 for 24 h also resulted in a reduction of GPDH activity to 81 +/- 5% (P < 0.05). On the other hand, 24-h exposure to 10 nmol/L IL-6 increased basal glycerol release by 42 +/- 12% (P < 0.01) and isoproterenol-induced glycerol release by 21 +/- 6% (P < 0.05). The same concentration of IL-6, however, did not alter basal or insulin-stimulated glucose transport. IL-6 secretion was acutely and chronically stimulated by 1 micromol/L isoproterenol (peak of 6.2-fold after 3 h; P < 0.001) and only moderately suppressed by 100 nmol/L cortisol (-36 +/- 10%; P < 0.001). In conclusion, human breast adipocytes release substantial amounts of IL-6 and express IL-6 receptor and gp130. The secretion of IL-6 by adipocytes is strongly stimulated by beta-adrenergic activation and is modestly suppressed by glucocorticoids. IL-6 reduces GPDH activity and stimulates lipolysis, suggesting an autocrine/paracrine role of this cytokine in human adipose breast tissue.
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PMID:Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function. 1134 40

Growing evidence obtained in recent years indicates that anaphylatoxin C5a receptors (C5aR) are not restricted to myeloid cells but are also expressed on nonmyeloid cells in different tissues such as brain, lung, skin and liver. In contrast to its well-defined systemic functions, the actions of anaphylatoxins in these organs are poorly characterized. The liver can be a primary target organ for the C5a anaphylatoxin since the liver is directly connected to the gut, via the mesenteric veins and portal vein which is a main source of complement activating lipopolysaccharides (LPS). In the normal rat liver, the C5aR is only expressed by nonparenchymal cells, i.e. strongly by Kupffer cells (KC) and hepatic stellate cells (HSC) and weakly by sinusoidal endothelial cells (SEC), but not expressed by the parenchymal hepatocytes (HC). Accordingly, direct effects of C5a were only found in the C5aR-expressing KC and HSC: C5a induced the release of prostanoids from KC and HSC and enhanced the LPS-dependent release of interleukin-6 from KC. These soluble mediators indirectly influenced effector functions of the C5aR-free HC. C5a enhanced the glycogen phosphorylase activity and thus the glucose output from HC indirectly via prostanoids released from KC and HSC. Glucose can serve as an energy substrate as well as an electron donor for the synthesis of reactive oxygen intermediates by KC. Moreover, C5a also enhanced transcription of the gene for the type-2 acute phase protein alpha 2-macroglobulin in HC indirectly by increasing LPS-dependent IL-6 release from KC. Under pathological conditions, C5aR was found to be upregulated in various organs including the liver. Simulation of inflammatory conditions by treatment of rats with IL-6, a main inflammatory mediator in the liver, caused a de novo expression of functional C5aR in HC. In livers of IL-6-treated rats, C5a initiated glucose output from HC and perhaps other HC-specific defense reactions directly without the intervention of soluble mediators from nonparenchymal cells.
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PMID:Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells. 1136 31

Conventional lactate (Lac)-buffered peritoneal dialysis (PD) solutions have turned out to be detrimental to human peritoneal cells, especially because of a low pH. In the present study, we focus on potential differences between Lac and bicarbonate (Bic) as a buffer when adjusted to a physiological pH. All test fluids were buffered with either 40 mmol/L of Lac or 34 mmol/L of Bic, sterile filtered, and adjusted to a pH of 7.4. Osmotic agents used were 1.36% glucose (Glu), 3.86% Glu, 1% amino acids (AA), and 7.5% Glu polymer (Glupoly). Human peritoneal mesothelial cells (HPMCs) were isolated from the omentum majus, grown to confluence, and incubated after the second passage for 15 minutes (37 degrees C and 5% carbon dioxide) with the test fluids. Cytotoxicity was controlled by measuring apoptotic and necrotic cells with cytofluorometry. Aerobic cell metabolism (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay) and intracellular adenosine triphosphate (ATP) concentrations were measured to assess cell viability. Release of interleukin-6 (IL-6) from HPMCs was determined as a parameter of cellular host defense. No significant difference in apoptosis or necrosis rates was found between the solutions adjusted to normal pH. However, in the MTT assay, Bic solutions were superior to corresponding Lac pendants at an identical pH of 7.4 (P < 0.01). Intracellular ATP concentrations reflected a very similar pattern (P < 0.05). Glupoly in combination with Lac showed an impaired pattern with both the MTT and ATP assays. Regarding IL-1beta-stimulated IL-6 release, there was a small, but not significantly better, response for Bic. Differences in manifest cell cytotoxicity reflected by apoptosis and necrosis rates could not be detected comparing PD solutions buffered with Lac or Bic at a physiological pH. However, distinct parameters of cell metabolism were superior with Bic compared with Lac. Especially Glupoly was inferior in combination with Lac as a buffer.
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PMID:Peritoneal dialysis fluids with a physiologic pH based on either lactate or bicarbonate buffer-effects on human mesothelial cells. 1157 93

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