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

The insulin secreting rat Rinm5F cells are often used to study the cytotoxic actions of interleukin-1 (IL-1) on pancreatic beta-cells. We demonstrate here that Rinm5F insulinoma cells express both type I and type II interleukin-1 receptor (IL-1R) mRNAs and gene products. IL-1R agonists, recombinant murine IL-1 alpha (rmIL-1 alpha, 10 ng/ml) and recombinant rat IL-1 beta (rrIL-1 beta, 100 pg/ml or 10 ng/ml) induce the upregulation of mRNA expression for both types of IL-1 receptors (IL-1Rs). This effect of rrIL-1 beta is antagonised by preincubation with recombinant human interleukin 1 receptor antagonist protein (rhIL-1ra, 5 micrograms/ml). Furthermore, this rrIL-1 beta induced upregulation of IL-1R mRNAs is blocked by actinomycin D (7.5 micrograms/ml), whereas cycloheximide (20 micrograms/ml) has no effect. The phorbol ester PMA (20 nM) upregulates the expression of mRNAs both IL-1 receptors, whereas glucose (50 mM) upregulates the expression of the type I IL-1R mRNA only. Pretreatment of cells with pertussis toxin (100 ng/ml) partially blocks the rrIL-1 beta induced expression of mRNA for the type I and, to a lesser extent, the type II IL-1R. Incubation of the cells with rrIL-1 beta also induces a time-dependent expression of c-fos, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) mRNAs. Binding studies with 125I-recombinant human IL-1 beta (125I-rhIL-1 beta) indicate that IL-1R gene products, with the ligand binding characteristics of the type I IL-1R, are constitutively present on Rinm5F cells. Treatment with rrIL-1 beta (6h) increases the number of 125I-rhIL-1 beta binding sites on Rinm5F cells. We have also demonstrated that the number of type II IL-1R binding sites increases after induction with rrIL-1 beta (6h), by indirect immunofluorescence using a monoclonal antibody (ALVA 42) raised against the human type II IL-1R. Furthermore, we have sequenced the type II IL-1R cDNA in the rat insulinoma Rinm5F cells. The comparison of the amino acid sequence of the rat type II IL-1R with that of the mouse and human type II IL-1Rs shows 90% and 62% amino acid identity, respectively. The most important difference between the human and murine type II IL-1Rs, and this rat type II IL-1R cDNA, is an open reading frame coding for a six amino acid longer, strongly charged (QIKEMK), cytosolic domain.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interleukin-1 stimulates the expression of type I and type II interleukin-1 receptors in the rat insulinoma cell line Rinm5F; sequencing a rat type II interleukin-1 receptor cDNA. 752 17

To eliminate the cytokines and leukocytes-induced proteases which could cause the multisystem organ failure postoperatively, we performed a preliminary hemodialysis to the priming solution and a continuous hemodialysis during extracorporeal circulation (ECC) in 5 children (HD group), and neither hemodialysis in another 5 children (Control group). We measured the plasma level of Interleukin-1 (IL-1), Interleukin-6 (IL-6) and leukocyte elastase (Ease) to evaluate the efficiency of these hemodialysis. Urine level of alpha 1-microglobulin (MG), beta 2-MG, urine volume, water balance and perfusion pressures during ECC were also measured to evaluate its protective effect for the renal function. IL-1 level significantly decreased in HD group 1 and 12 hours after operation. Not only IL-6 and Ease during ECC but also alpha 1- and beta 2-MG 1 hour after operation decreased in HD group so hemodialysis could be useful to eliminate the cytokines. Ease and could protect the renal function. Water balance and perfusion pressures also obtained good results with these hemodialysis. Plasma osmolality and glucose level changed within the normal range in HD group, conversely over the normal range in control group. We conclude this method is useful for neonatal, ECC.
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PMID:[Efficiency of the preliminary and continuous hemodialysis at open heart surgery in infants and children]. 761 27

The role of interleukin-6 (IL-6) in carbohydrate metabolism beyond its inhibition of hepatic phosphoenolpyruvate carboxykinase has not been widely pursued. To describe such IL-6 effects, we examined in the rat the responses of plasma corticosterone, glucagon, insulin, and glucose levels and the hepatic glycogen content 30, 60, 90, 120, and 180 min after intravenous injection of recombinant human IL-6. The effect to increase plasma corticosterone was consonant with the well-known action of IL-6 on the hypothalamus-pituitary-adrenal cortex. IL-6 produced a transient increase in plasma glucagon that was mirrored by elevated plasma glucose and a depletion of hepatic glycogen. Plasma insulin levels were not elevated within the first hour after IL-6 injection but were significantly elevated 90 min and beyond. We suggest that the stimulus for increased circulating insulin was elevated plasma glucose, rather than a direct effect of IL-6. The results demonstrate that IL-6, acting directly on peripheral organs and/or through the central nervous system (CNS) can alter the hormonal and carbohydrate milieu. We propose that these actions of IL-6 are one aspect of its role in the acute phase response.
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PMID:Endocrine and carbohydrate responses to interleukin-6 in vivo. 762 63

We examined the measurement and the diagnostic value of cerebrospinal fluid interleukin-6 (CSF IL-6) in meningitis. The cytokine was measured by bioassay (B9 hybridoma cell line) and by immunoassay (in-house radioimmunoassay). We compared the diagnostic value of CSF IL-6 determination with that of other biochemical markers of meningitis. Although there was significant correlation between bioactive and immunoactive IL-6 (r = 0.724, P < 0.001), results were frequently different with biological/immunological ratios ranging from 0.2 to 24.3 (mean 4.6). Gel permeation chromatography suggested that the discrepancy in biological and immunological activities was not due to molecular heterogeneity, but may be explained by the presence of a synergistic factor. Interleukin-6 concentration was markedly elevated in CSF from most patients with bacterial meningitis compared to patients with viral meningitis and those without evidence of infection. However, low IL-6 levels by radioimmunoassay did not exclude bacterial meningitis (sensitivity 86%). CSF total protein and CSF glucose were significantly different between all three groups, but there was no significant difference in lactate concentration between virally infected and normal CSF, both of which had lower lactate concentrations than those in bacterial infection. CSF IL-6 measurement had greater sensitivity, specificity and predictive value than these other biochemical markers, and hence a rapid assay for IL-6 in CSF may contribute to the early diagnosis of bacterial infection.
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PMID:Cerebrospinal fluid interleukin-6 and its diagnostic value in the investigation of meningitis. 763 33

The control of metallothionein (MT) synthesis was investigated in freshly prepared rat hepatocytes in experiments of short-term duration. Viability and metabolic function were maintained in incubations of 6-h duration. MT synthesis was measurable in hepatocytes from fed rats at Zn concentrations down to 1 microM. Zn and dexamethasone induced concentration-dependent increases in the synthesis of MT with maximal increases above the 5-h control of 3.2- and 2.5-fold, respectively. Zn induction of MT was first measurable at 2 h and was inhibited by actinomycin C. Although initial (0 h) MT concentrations in hepatocytes from fasted rats were double those from fed rats, after 6-h incubation in the presence of 50 microM Zn, the fasted rat hepatocytes showed only half the MT concentrations of the fed rat hepatocytes. Glucagon and interleukin-6 (IL-6) were less effective inducers and increased MT synthesis by 28 and 17%, respectively. IL-6 (100 U/mL) was found to have an additive effect on MT synthesis above that of Zn alone (1-50 microM) or Zn plus dexamethasone (1 microM). A supernatant from LPS-stimulated macrophages increased MT synthesis by 40%. The basal MT synthesis was not increased by either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1). All incubations were carried out in the presence of RPMI 1640 medium with Hepes (20 mM), bicarbonate (24 mM), and fatty acid-free albumin (FAFA; 0.5% w/v). MT synthesis was also seen using Krebs bicarbonate buffer with glucose (10 mM), Hepes (20 mM), and FAFA (0.5% w/v), and although the level of MT synthesis was less than in RPMI, the increases in concentrations of MT at 5 h were 225, 139, 36 and 20% for Zn, dexamethasone, glucagon, and control, respectively. It is concluded that MT synthesis occurs in freshly prepared hepatocytes and that these cells are responsive to some of the established inducers of MT. This system enables the study of MT synthesis in individual rats in various metabolic and pathological states.
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PMID:Metallothionein induction in freshly isolated rat hepatocytes. 768 80

To clarify the mechanism that causes elevation of plasma fibrinogen levels in diabetes, we examined the effect of high concentration of glucose and/or advanced glycosylation end products (AGEs) on the production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by human monocytes. Monocytes isolated from nine healthy volunteers were incubated with glucose, glucose with mannitol, or glucose with AGE-BSA for 24 or 48 h, respectively. IL-6 and TNF-alpha levels of culture supernatants were measured by ELISA methods. IL-6 and TNF-alpha levels of culture supernatants incubated with 22 mM or 33 mM glucose showed considerable increase over basal levels incubated with 11 mM glucose, whereas those levels incubated with high concentration of mannitol showed no increase. These two cytokine levels of culture supernatants, especially IL-6 level, showed synergistic elevation with AGE-BSA concentration. Our serial observation with treatment for lowering glucose levels showed that the diabetics with decreasing plasma fibrinogen levels also showed decrease in plasma IL-6 levels. In this study, we revealed the effect of glucose and AGEs on the production of IL-6 or TNF-alpha by human monocytes. These results suggest that hyperglycemia and AGEs will cause disregulated production of IL-6 and hyperfibrinogenemia in diabetics.
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PMID:The effect of glucose and advanced glycosylation end products on IL-6 production by human monocytes. 769 4

Cytokines are a group of regulatory and immunomodulatory proteins involved in a number of physiological processes. Various disease states are believed to involve alteration of normal cytokine activity, including insulin-dependent diabetes mellitus, an autoimmune disease in which insulin secreting beta cells within pancreatic islets of Langerhans are selectively destroyed. Glucose-induced insulin secretion is inhibited by the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 and tumour necrosis factor alpha (TNF) when combined with IL-1 beta in cultured rat islets, by IL-1 beta, TNF and interferon gamma in mouse islets, and by combined treatment of IL-1 beta, TNF and interferon gamma in human islets. Continued cytokine treatment in many cases leads to destruction of some, if not all, islet cells. A key factor in the inhibitory effect of IL-1 beta and TNF in rat islets is the generation of nitric oxide which inactivates enzymes such as aconitase and ribonucleotide reductase by formation of iron-nitrosyl complexes. This in turn may lead to reduced oxidation of glucose and synthesis of ATP and DNA respectively. The causes of cytokine-induced beta cell death are less well defined, but important factors may be nitric oxide-mediated DNA damage, depletion of NAD levels and toxic effects of oxygen free radicals and eicosanoids generated in addition to nitric oxide. Potentially important defence and repair responses induced by IL-1 beta treatment of rat islets are formation of heat shock protein, haem oxygenase, and superoxide dismutase. Other protective responses may be induction of cytokines and cytokine receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines, nitric oxide and insulin secreting cells. 775 73

Interleukin-6 (IL-6) is one of the major circulating cytokines in catabolic states. To investigate its endocrinologic and metabolic actions in vivo, we studied eight patients with metastatic renal cell cancer two times, once during infusion of saline (control) and once during a 4-h infusion of 150 micrograms recombinant human IL-6 (rhIL-6). Rates of appearance (Ra) of glucose and free fatty acids (FFA) in plasma were measured by using the isotope dilution method. Energy expenditure and substrate oxidation were determined by indirect calorimetry. rhIL-6 induced increases in plasma norepinephrine (+261 +/- 97%, P < 0.001), cortisol (+210 +/- 48%, P < 0.001), and glucagon (+70 +/- 18%, P < 0.001), in resting energy expenditure (+25 +/- 2%, P < 0.001 vs. control), and in plasma FFA concentration (+60 +/- 30%, P < 0.001), FFA Ra (+105 +/- 18%, P < 0.001), and fat oxidation (+38 +/- 16%, P < 0.001). Glucose Ra increased by 20 +/- 5% (P < 0.01) during rhIL-6 infusion with a concomitant increase in the metabolic clearance rate of glucose. In conclusion, our data demonstrate that rhIL-6 induces many of the endocrinologic and metabolic changes found in catabolic states and thus may mediate some of the metabolic effects previously ascribed to other cytokines.
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PMID:Endocrinologic and metabolic effects of interleukin-6 in humans. 776 32

beta 2-Microglobulin (beta 2M) is a major component forming amyloid deposits in patients with hemodialysis-associated amyloidosis (HAA), a serious complication of long-term hemodialysis. Recently, we demonstrated that beta 2M modified with the Maillard reaction is a definite constituent of amyloid deposits in patients with HAA. Our further study demonstrated that this modified beta 2M induces not only chemotaxis of monocytes but also secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 from macrophages, suggesting the potential link of glycation of beta 2M by the Maillard reaction to the pathogenesis of HAA. The present study was undertaken to identify the glycated site(s) of beta 2M purified from long-term hemodialysis patients as well as beta 2M incubated with glucose in vitro. Borotritide-treated beta 2M was cleaved by endoproteinase Lys-C, and peptides were isolated by reverse-phase high-performance liquid chromatography, followed by amino acid sequence analysis and fast atom bombardment mass spectrometry to identify the glycated site. The glycated sites of beta 2M formed in vivo were found to be almost the same as those of glycated beta 2M in vitro. The primary glycated site was the alpha-amino group of the amino terminal isoleucine. Other minor sites were the epsilon-amino groups of Lys-19, -41, -48, -58, -91, and -94. Computer graphics of the three-dimensional structure of beta 2M suggested that the high specificity for the glycated site at Ile-1 may be explained by its high solvent accessibility and the nearby imidazole group of His-31 as an acid-base catalyst of the Amadori rearrangement.
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PMID:Glycation of human beta 2-microglobulin in patients with hemodialysis-associated amyloidosis: identification of the glycated sites. 791 43

Cytokines seem to play an important role in the metabolic disturbances that are commonly associated with sepsis. In this study, we analyzed the effect of tumor necrosis factor, interleukin-1 and interleukin-6, as well as that of tumor necrosis factor in combination with interleukin-1 or interleukin-6, both on free fatty acids and on phospholipid synthesis by isolated rat hepatocytes. All three cytokines and combinations caused inhibited D-[U-14C]glucose incorporation into phosphatidylcholine (tumor necrosis factor = 6.39 +/- 1.13 pmol/microgram protein vs. control = 12.90 +/- 0.98 pmol/microgram protein, n = 7; p < 0.001). However, when [U-14C]palmitate was used as radioactive precursor, tumor necrosis factor, either alone or in the presence of the other cytokines, stimulated phosphatidylcholine synthesis. D-[U-14C]glucose incorporation into free fatty acids and triacylglycerol was also significantly stimulated, whereas phosphatidylinositol labeling was found inhibited by the assayed cytokines. Our results demonstrate an effect of sepsis-related cytokines, more evident for tumor necrosis factor, on hepatocyte lipid synthesis either from glucose or palmitate. Also, the findings support the hypothesis that cytokine-induced changes in hepatocyte lipid synthesis can contribute to the impairment in lipidic metabolism seen in patients with sepsis.
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PMID:Effect of different sepsis-related cytokines on lipid synthesis by isolated hepatocytes. 792 34


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