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)

Proinflammatory cytokines are implicated as effector molecules in the pathogenesis of IDDM. Interleukin-6 (IL-6) alone or in combination with IL-1beta inhibits glucose-stimulated insulin release from isolated rat pancreatic islets by unknown mechanisms. Here we investigated 1) if the effects of IL-6 are mimicked by ciliary neurotrophic factor (CNTF), another member of the IL-6 family of cytokines signaling via gp130, 2) the possible cellular mechanisms for these effects, and 3) if islet endocrine cells are a source of CNTF. CNTF (20 ng/ml) potentiated IL-1beta-mediated (5-150 pg/ml) nitric oxide (NO) synthesis from neonatal Wistar rat islets by 31-116%, inhibition of accumulated insulin release by 34-49%, and inhibition insulin response to a 2-h glucose challenge by 31-36%. CNTF potentiated IL-1beta-mediated NO synthesis from RIN-5AH cells by 83%, and IL-1beta induced islet inducible NO-synthase (iNOS) mRNA expression fourfold. IL-6 (10 ng/ml) also potentiated IL-1beta-mediated NO synthesis and inhibition of insulin release, whereas beta-nerve growth factor (NGF) (5 or 50 ng/ml) had no effect. mRNA for CNTF was expressed in rat islets and in islet cell lines. In conclusion, CNTF is constitutively expressed in pancreatic beta-cells and potentiates the beta-cell inhibitory effect of IL-1beta in association with increased iNOS expression and NO synthesis, an effect shared by IL-6 but not by beta-NGF. These findings indicate that signaling via gp130 influences islet NO synthesis associated with iNOS expression. We hypothesize that CNTF released from destroyed beta-cells during the inflammatory islet lesion leading to IDDM may potentiate IL-1beta action on the beta-cells.
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PMID:Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase. 975 98

To evaluate whether interferon-gamma (IFN-gamma) is involved in the interaction between the immune and endocrine systems in vivo, we studied six healthy subjects twice in a placebo-controlled trial: once after administration of recombinant human IFN-gamma and, on another occasion, after administration of saline. The rate of appearance of glucose was determined by infusion of [6,6-2H2]glucose and resting energy expenditure by indirect calorimetry. Human leukocyte antigen-DR gene expression on monocytes and serum neopterin increased after administration of IFN-gamma (P < 0.05 vs. control). IFN-gamma increased serum interleukin-6 levels significantly. Levels of tumor necrosis factor-alpha remained below detection limits. IFN-gamma increased plasma concentrations of ACTH and cortisol (P < 0.05 vs. control), IFN-gamma did not alter concentrations of growth hormone, (nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growth factor I. IFN-gamma did not alter plasma concentrations of glucose and free fatty acids nor the rate of appearance of glucose. IFN-gamma increased resting energy expenditure significantly. We conclude that IFN-gamma is a minor stimulator of the endocrine and metabolic pathways. Therefore, IFN-gamma by itself is probably not a major mediator in the interaction between the immune and the endocrine and metabolic systems.
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PMID:Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic effects in humans. 993 Nov 85

Stress mediators play a major role in inducing the hypermetabolic stress state in the liver after major injuries. The majority of studies on the effect of mediators on hepatocytes have focused on single factor effects or on the effect of very complex additives (e. g., serum), and there are no reports which have rigorously identified specific interactions between stress mediators. We used a factorial design experimental approach to evaluate the effects of a four to five day exposure to hormone (glucagon, hydrocortisone, and epinephrine) and cytokine [tumor necrosis factor-alpha (TNF-alpha) interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)] stress mediators on stable cultures of rat hepatocytes. Both individual-factor effects and two factor interactions on the metabolism of urea, glucose, lactate, ketone bodies, albumin, and fibrinogen were evaluated. The cultured hepatocyte model exhibited physiologic responses to the applied stress mediators. While hydrocortisone and epinephrine had no effect, glucagon induced an increase in glucose and urea synthesis. Interleukin-6 increased fibrinogen and decreased albumin production. Furthermore, IL-6 and glucagon caused an increase in the ketone-body ratio (KBR = [acetoacetate]/[beta-hydroxybutyrate]), which is in equilibrium with the intramitochondrial NAD+/NADH. Tumor necrosis factor-alpha and IL-1beta, on the other hand, decreased the KBR. An important two-factor interaction between IL-1beta and IL-6 was identified, namely that IL-1beta effectively negates the positive effect of IL-6 on the KBR when both are present. These results provide further understanding of the effect of stress mediators on hepatic function and metabolism. These effects may have important implications in the pathogenesis of progressive organ dysfunction which often follows prolonged inflammatory states triggered by major injuries.
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PMID:Metabolic effects of stress mediators on cultured hepatocytes. 1019 93

A serious insulin resistance characterizes pancreatic cancer-associated diabetes mellitus. Elsewhere, we demonstrated that MIA PaCa2 cultured cells secrete a soluble factor responsible for reduced glucose tolerance induced in SCID mice. The intracellular mechanism of insulin resistance was investigated in isolated and perfused rat hepatocytes incubated with MIA PaCa2 conditioned medium. Lactate production was reduced compared to hepatocytes incubated with control medium while 1,2-DAG was increased and PKC was activated in the hepatocytes incubated with MIA PaCa2 conditioned medium. This behavior was not reproduced treating the hepatocytes with the growth factors EGF, interleukin Ibeta, interleukin-6, and TGF-beta1. In an attempt to make a biochemical identification of the hypothesized tumor associated-diabetogenic factors we observed a low molecular weight protein in the conditioned medium, absent in the nonconditioned one, that may be responsible for the described behaviors.
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PMID:Glucose metabolic alterations in isolated and perfused rat hepatocytes induced by pancreatic cancer conditioned medium: a low molecular weight factor possibly involved. 1019 61

A new model of cachexia is described in which muscle protein metabolism related to the ubiquitin-proteasome pathway was investigated. Cloning of the colon-26 tumor produced a cell line, termed R-1, which induced cytokine (noninterleukin-1beta, interleukin-6 and tumor necrosis factor-alpha)-independent cachexia. Implantation of R-1 cells in mice elicited significant (20-30%) weight loss and decreased blood glucose by 70%, and adipose tissue levels declined by 95% and muscle weights decreased by 20-25%. Food intake was unaffected. The decrease in muscle weight reflected a decline in insoluble, but not soluble, muscle protein that was associated with a significant increase in net protein degradation. The rate of ubiquitin conjugation of proteins was significantly elevated in muscles of cachectic mice. Furthermore, the proteasome inhibitor lactacystin blocked the increase in protein breakdown but had no significant effect on proteolysis. Several markers of the ubiquitin-proteasome pathway, E2(14k) mRNA and E2(14k) protein and ubiquitin-protein conjugates, were not elevated. Future investigations with this new model should gain further insights into the mechanisms of cachexia and provide a background to evaluate novel and more efficacious therapies.
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PMID:A new model of cancer cachexia: contribution of the ubiquitin-proteasome pathway. 1044 30

The objective of this study was to determine whether the measurements of amniotic fluid nitric oxide metabolite (NOx: nitrate + nitrite) concentrations could be a clinically useful marker to differentiate between intra-amniotic mycoplasma and nonmycoplasma infections. Amniocentesis was performed on 76 pregnant women with suspicion of intra-amniotic infection. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture with either mycoplasma or nonmycoplasma infections. Rapid amniotic fluid tests for Gram stain, glucose, leukocyte counts, interleukin-6, and NOx were performed. Amniotic fluid NOx was measured with aspergillus nitrate reductase and Griess reagent. Interleukin-6 was determined by enzyme immunoassays. Amniotic fluid NOx and interleukin-6 were normalized by amniotic fluid creatinine levels. Patients with intra-amniotic mycoplasma (n = 7) and nonmycoplasma infections (n = 8) had significantly higher amniotic fluid leukocyte counts and interleukin-6 concentrations and significantly lower amniotic fluid glucose levels than noninfected controls (n = 61). Amniotic fluid concentrations of NOx were significantly higher in those with intraamniotic nonmycoplasma infection as compared to those with intraamniotic mycoplasma infection and noninfected controls (NOx: 3.35+/-0.74 vs. 2.03+/-0.41 micromol/mg creatinine, p = 0.005, and 3.35+/-0.74 vs. 1.72+/-0.07 micromol/mg creatinine, p < 0.0001, respectively). However, patients with intra-amniotic mycoplasma infection did not differ significantly from noninfected controls. Our data indicate that clinical characteristics of intra-amniotic mycoplasma infection may differ from intra-amniotic nonmycoplasma infection. As delivery is not always indicated in intra-amniotic mycoplasma infection, elevated rapid amniotic fluid tests (leukocyte counts, interleukin-6, and glucose) may not be appropriate in the clinical management of intra-amniotic mycoplasma infection. In addition to these rapid amniotic fluid tests, incorporation of the measurement of amniotic fluid NOx may be of clinical importance in the differentiation and management of patients with suspected intra-amniotic mycoplasma and nonmycoplasma infection.
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PMID:Nitric oxide: a clinically important amniotic fluid marker to distinguish between intra-amniotic mycoplasma and non-mycoplasma infections. 1045 27

This study assessed glucose tolerance, insulin sensitivity and lipid parameters in HIV-infected patients presenting with lipodystrophy during HAART including protease inhibitors. Fourteen consecutive patients from Rothschild Hospital treated with HAART and presenting with marked facial lipoatrophy were evaluated. A 75 g oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, proinsulin and free fatty acids at T0, 30, 60, 90 and 120 min was performed. Lipid parameters (triglycerides, cholesterol, apolipoproteins A1 and B) were studied as well as nutritional and inflammatory markers (albumin, prealbumin, transferrin, haptoglobin, orosomucoid, C-reactive protein), endocrine and cytokine parameters (thyrotropin, cortisol, leptin, interleukin-6), HIV viral load and CD4-lymphocyte count. These patients were compared with 20 non-lipodystrophic protease inhibitor-treated patients. The measurements performed during OGTT showed that among the 14 lipodystrophic patients, 11 (79%) presented with diabetes (5 patients) or normal glucose tolerance but with insulin resistance (6 patients). This frequency was strikingly different in the group of nonlipodystrophic patients, which included only 4 (20%) presenting with diabetes (1 patient), or impaired glucose tolerance (2 patients), or normal glucose tolerance but with insulin resistance (1 patient). Hypertriglyceridaemia was present in 11 lipodystrophic (79%) versus 7 nonlipodystrophic patients (35%). Nutritional and endocrine measurements were normal. An abnormal processing of proinsulin to insulin was excluded. Thus, lipodystrophy during HAART was associated with diabetes, insulin resistance and hypertriglyceridaemia. Diabetes, diagnosed by basal and/or 120 min-OGTT glycaemia, seems more frequent than previously described. The therapeutic consequences of these results deserve evaluation in clinical trials.
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PMID:Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). 1049 91

The influence of the glutathione precursor, l-2-oxothiazolidine-4-carboxylic acid (OTZ), on the function of human peritoneal mesothelial cells in vitro, in conditions that mimic the in vivo effect of peritoneal dialysis solutions on mesothelium, was studied. Mesothelial monolayers were exposed to dialysis fluids (Dianeal 1.36 or Dianeal 3.86; Baxter Healthcare Corp, Round Lake, IL) that were diluted gradually with pooled-effluent dialysate obtained from patients undergoing continuous ambulatory peritoneal dialysis. In vitro exposure of mesothelium to standard dialysis fluid enhances their susceptibility to injury by hydrogen peroxide. OTZ added to dialysis solution in concentrations of 1 mmol/L prevented the toxic effect of hydrogen peroxide, probably by increasing intracellular glutathione. Mesothelial cells exposed to dialysis fluid become activated, evidenced by increased release of interleukin-6 and hyaluronan. OTZ used in concentrations of 1 mmol/L reduced that effect. Furthermore, the addition of glucose to the culture medium in a concentration of 45 mmol/L inhibits the proliferation of mesothelial cells; the presence of OTZ, 1 mmol/L, partially prevents the inhibitory effect of glucose. The results presented in this report show that by augmenting the intracellular concentration of glutathione in mesothelial cells by the addition of OTZ to the dialysis fluid, we can increase their resistance to the acute toxicity of free radicals and long-term toxicity of glucose. In addition, mesothelial cells with an increased glutathione level are less activated after their exposure to dialysis fluid.
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PMID:l-2-oxothiazolidine-4-carboxylic acid modulates function of peritoneal mesothelial cells in vitro. 1051 47

Fat tissue is a significant source of endogenous tumor necrosis factor alpha (TNFalpha), the pluripotent cytokine that plays an important role as a mediator of the peripheral insulin resistance found in obesity. The majority of evidence for this role of TNFalpha is from studies in animal models of obesity. To explore further the role of TNFalpha in the pathogenesis of obesity-related insulin resistance in humans, we compared plasma levels of TNFalpha and the other main endocrine cytokine, interleukin-6 ([IL-6] both measured by enzyme-linked immunosorbent assay), in 26 obese women (body mass index [BMI] > 30 kg/m2) and 13 female controls (BMI < 26 kg/m2) without a history of recent or active infection. Glucose and insulin levels were measured at 0, 1, and 2 hours after a 75-g oral glucose load. There was no significant difference in plasma TNFalpha or IL-6 levels between obese and non-obese subjects overall (2.10 +/- 0.19 v 1.65 +/- 0.18 pg/mL and 2.06 +/- 0.29 v 1.50 +/- 0.17 pg/mL, respectively). However, TNFalpha levels were significantly elevated in obese subjects with a 2-hour glucose level more than 140 mg/dL (n = 8) compared with the other obese subjects (n = 18) and the non-obese controls (2.88 +/- 0.46 v 1.75 +/- 0.10 and 1.65 +/- 0.18 pg/mL, respectively, P < .01). Furthermore, the TNFalpha level correlated significantly with the waist to hip ratio ([WHR] r = .53, P < .01) and fasting and post-oral glucose tolerance test (OGTT) insulin levels (r = .47, P < .02), but not with the BMI, and was higher in obese women with a WHR more than 0.90 (n = 14) in comparison to those with a WHR less than 0.90 (n = 12, 2.47 +/- 0.29 v 1.66 +/- 0.18 pg/mL, respectively, P < .03). The corresponding plasma leptin level was significantly higher in obese women versus the control group (41.6 +/- 2.5 v22.3 +/- 2.9 ng/mL, P < .001) and was related to the BMI (r = .60, P < .01) but not to TNFalpha or the WHR. There were no significant differences in the corresponding IL-6 concentration between groups, and IL-6 did not correlate with TNFalpha, leptin, BMI, WHR, or insulin levels. In conclusion, circulating TNFalpha levels are higher in abdominal obesity compared with peripheral obesity, and may contribute to the insulin resistance that more commonly complicates the former pattern of fat distribution.
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PMID:Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. 1053

We compared the endocrine and metabolic changes during acute emergency abdominal surgery performed using either laparoscopy or laparotomy in children. Twenty-nine children aged 1.5-14 years were assigned to undergo laparoscopy (n = 15) or laparotomy (n = 14) with a standard anaesthesia technique. Arterial blood gases and blood prolactin, cortisol, interleukin-6, glucose, insulin, lactic acid and epinephrine levels were determined 5 min after the induction of anaesthesia, 30 min into surgery and at the end of surgery. Intra-operative heart rate and mean arterial pressure were stable in both groups. In the laparoscopy group, slight respiratory acidosis occurred during surgery (p < 0.01) but there were no changes in the laparotomy group. Insulin, cortisol, prolactin, epinephrine, lactate and blood glucose levels increased in both groups (p < 0.05) although there was no difference between the groups. The surgical stress and trauma imposed by laparoscopy seems similar to that caused by laparotomy in children undergoing emergency abdominal surgery.
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PMID:Systemic stress response during operations for acute abdominal pain performed via laparoscopy or laparotomy in children. 1086 58


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