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 diabetes mellitus (DM) show an increased susceptibility to bacterial infections due to the presence of neutrophil dysfunction. Susceptibility to tuberculosis has also been reported in such patients, however, the reason remains unclear. This study measured the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) by the peripheral monocytes of patients diagnosed with pulmonary tuberculosis accompanied by DM (TB+DM) and patients without DM complications (TB) using age-matched, healthy control subjects for comparison. Also examined was the relationship between cytokine production and DM control. The results were as follows: (1) The production of IL-1 beta, TNF alpha and IL-6 in TB patients was significantly higher than that observed in the healthy control subjects. (2) The production of IL-1 beta, TNF alpha and IL-6 in TB+DM patients was significantly lower than that observed in the TB patients. (3) The production of IL-1 beta and TNF alpha in TB+DM patients with poor control was significantly lower than that observed in the patients with good control. (4) The TNF alpha production had a significant inverse correlation to HbA1c in the TB+DM patients. This study demonstrated that the production of cytokines is impaired in TB+DM patients and suggests a close correlation between tuberculosis immunity and DM.
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PMID:[Case study of interleukin-1 beta, tumor necrosis factor alpha and interleukin-6 production peripheral blood monocytes in patients with diabetes mellitus complicated by pulmonary tuberculosis]. 129 80

In this study, we demonstrate that low but not high concentrations of interleukin-6 (IL-6) potentiate the cytotoxic effect of tumour necrosis factor-alpha (TNF-alpha) on U937 cells, in a dose-dependent manner. Killing of U937 cells by 100 U/ml of TNF-alpha, was maximally potentiated by 50 U/ml of IL-6. No potentiation of cell killing was observed when the concentration of IL-6 was increased to 4000 U/ml. At a concentration of 50 U/ml, IL-6 up-regulated TNF receptor expression but no change in TNF receptor number was observed when the concentration of IL-6 was increased to 4000 U/ml. Low concentrations of IL-6 can also induce sub-cytotoxic doses of TNF-alpha (0.1 and 0.33 U/ml) to kill U937 cells. Up-regulation of TNF receptors by IL-6 is dependent on de novo protein synthesis since receptor induction is abolished in the presence of cycloheximide. Taken together the data suggest that the potentiation of cell killing observed by a combination of these lymphokines is mediated in part by IL-6-induced changes in TNF receptor expression.
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PMID:Interleukin-6 regulates the cytotoxic effect of tumour necrosis factor on U937 cells. 131 49

The study objectives were to investigate serum levels of interleukin-6 and C-reactive protein (CRP) after liver transplantation to correlated measurements with various clinical parameters. Twenty-three patients were studied after orthotopic liver transplantation. Serum IL-6 activity was evaluated by testing its capacity to induce proliferation of the IL-6-dependent hybridoma cell line B9. CRP was assessed by a nephelometric method. Only two of seven patients with acute cellular rejection developed an increase of serum IL-6 and CRP. In contrast to this rejection group, elevated IL-6 levels were observed in 7/9 patients with bacterial infections. Peak values for IL-6 were observed one day and for CRP two days after clinical diagnosis of infection. CMV disease was also associated with markedly increased IL-6 and CRP levels in 5/7 patients. Surprisingly, levels in this condition were approximately in the same range as in bacterial infection. IL-6 and CRP serum levels seen in bacterial infection and CMV disease were significantly higher than those in rejection (P less than 0.001). Serum IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6. Preferential elevations of IL-6 and CRP represent one feature of bacterial and viral infections. Elevation of TNF during rejection as described earlier is only rarely accompanied by increased serum IL-6 levels.
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PMID:Circulating serum levels of interleukin 6 and C-reactive protein after liver transplantation. 132 19

We have previously reported that recombinant human interleukin-1 (IL-1) stimulates matrix erosion in bovine nasal cartilage explants (R. J. Smith et al., Inflammation 13, 367-382, 1989). This action of IL-1 is believed to be caused by matrix-degrading neutral proteinases produced by activated chrondrocytes. Accordingly, we investigated the effects of recombinant human interleukin-1 alpha (IL-1 alpha), recombinant human interleukin-1 beta (IL-1 beta), and recombinant human tumor necrosis factor alpha (TNF alpha) on bovine nasal chondrocyte (BNC) responsiveness. IL-1 alpha and IL-1 beta stimulated a time (0-72 hr) and concentration-dependent (0.01-10 ng/ml) production of collagenase, gelatinase, caseinase, and prostaglandin E2 (PGE2) in BNC monolayer cultures. Neutral proteinase and PGE2 production by BNC was also induced by TNF alpha (0.2-200 ng/ml) in a time-dependent (0-72 hr) manner. Recombinant human interleukin-6 (IL-6) caused a concentration-dependent (6-200 ng/ml) potentiation of IL-1-stimulated neutral proteinase and PGE2 production by BNC. However, recombinant human platelet-derived growth factor homodimer BB suppressed BNC responsiveness to IL-1. A recombinant human IL-1 receptor antagonist protein inhibited BNC activation by IL-1 but not TNF alpha.
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PMID:Induction of neutral proteinase and prostanoid production in bovine nasal chondrocytes by interleukin-1 and tumor necrosis factor alpha: modulation of these cellular responses by interleukin-6 and platelet-derived growth factor. 132 6

Okadaic acid, a phosphatase inhibitor from a marine organism, mimics tumor necrosis factor/interleukin-1 (TNF/IL-1) in inducing changes in early cellular protein phosphorylation. A total of approximately 116 proteins exhibit significant and concordant changes in phosphorylation or dephosphorylation within 15 min in human fibroblasts activated by either okadaic acid, TNF, or IL-1. The fidelity of this mimicry by okadaic acid extends to the phosphorylation of the 27 hsp complex, stathmin, eIF-4E, myosin light chain, nucleolin, epidermal growth factor receptor, and other cdc2-kinase substrates (c-abl, RB, and p53). The okadaic acid-induced pattern of protein phosphorylation is distinct from that observed in cells treated with phorbol 12-myristate 13-acetate or with ligands like epidermal growth factor, cyclic AMP agonists, bradykinin, or interferons. Like TNF, okadaic acid also induces the transcription of immediate early response genes like c-jun and Egr-1 as well as the interleukin-6 genes. The overall early effects of okadaic acid uniquely parallel those of TNF/IL-1 and not those of other cytokines or ligands. Regulation of protein phosphatase inhibition is discussed as a mechanism for TNF/IL-1 signal transduction.
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PMID:Okadaic acid mimics multiple changes in early protein phosphorylation and gene expression induced by tumor necrosis factor or interleukin-1. 137 Apr 82

In the present report, we show that progressive growth of the immunogenic C57BL/6J sarcoma, MCA/76-9, was accompanied by an increase in serum interleukin-6 (IL-6) activity. The possible pathways leading to the induction of IL-6 release by the tumor cells are described. It was shown that macrophage products IL-1 alpha, IL-1 beta, and to a lesser extent, TNF alpha, induced the tumor cells in vitro to transcribe the IL-6 gene and release the gene product. IL-1 induced significantly more IL-6 mRNA and bioactivity than TNF alpha, although both cytokines induced a cumulative increase of bioactivity in the supernates over a period of 24 h. The tumor cells were shown to express receptors for IL-1 alpha, which could be blocked with anti-IL-1 receptor antibody. Given the previous reports that tumor-associated macrophages expressed both IL-1 alpha/beta and TNF alpha, the data suggest, first, that the mutual interaction of tumor cells and macrophages in situ may contribute to the observed increase in circulating IL-6 activity, and second, that the release of IL-6 in vivo may serve to regulate both anti-tumor immune responses and suppressor mechanisms.
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PMID:Tumor cell IL-6 gene expression is regulated by IL-1 alpha/beta and TNF alpha: proposed feedback mechanisms induced by the interaction of tumor cells and macrophages. 140 92

Cytokines are immunoregulatory molecules that are important mediators of the host response to stress and infection. Infants and children undergoing major surgery are particularly at risk of developing sepsis and have altered metabolic responses to surgical stress compared to adults. We have investigated the temporal sequence of cytokine responses in six infants (mean age, 11 +/- 7.5 months) undergoing pull-through operation for Hirschsprung's disease and correlated them with hemodynamic and biochemical parameters. Tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA preoperatively, intraoperatively (hourly), and 24 and 48 hours postoperatively. IL-6 levels increased significantly in all cases within 2 hours of commencement of the operation (P less than .01) and were maximal 24 hours postoperatively. No significant changes in IL-1 beta levels (mean range, 70 to 110 pg/mL) were seen in these patients. TNF levels were undetectable (less than 20 pg/mL) throughout the study. Cortisol levels were increased in all patients during operation. Serum C-reactive protein levels were first detected 24 hours postoperatively and continued to increase 48 hours postoperatively. Hemodynamically, heart rate increased during the first 3 hours of operation and correlated with increase in IL-6 levels. Blood pressure and temperature changes did not correlate with cytokine levels. This study identifies IL-6 as the earliest detectable cytokine response associated with major surgery in infants. It also suggests that IL-6 can be unregulated, independently of other cytokines, in response to surgical stress.
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PMID:Early induction of IL-6 in infants undergoing major abdominal surgery. 140 30

The current study focused on the effect of continuous ambulatory peritoneal dialysis (CAPD) dialysate obtained following different intraperitoneal dwell periods on the release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) from mononuclear leukocytes (PBMC). Aliquots of 5 x 10(6)/ml healthy peripheral PBMC were exposed to fresh or spent CAPD dialysate (10-240 min of intra-peritoneal dwell) and stimulated with Escherichia coli endotoxin (10 micrograms/ml, 2h). IL-6 and TNF alpha in cell supernatants were determined by specific enzyme immunoassays. Control PBMC in physiological buffer released 361 +/- 70 pg/ml IL-6 and 717 +/- 147 pg/ml TNF alpha (mean +/- SEM, n = 8), whereas exposure to fresh dialysis fluids severely suppressed cytokine release from PBMC (less than 30 pg/ml IL-6 and less than 15 pg/ml TNF alpha). A significant inhibition of IL-6 and TNF alpha release was also observed in PBMC exposed to spent dialysate. The inhibitory capacity of the spent fluids was pronounced with increasing intra-peritoneal dwell time (10 min: 183 +/- 45 pg/ml IL-6 and 538 +/- 109 pg/ml TNF alpha; 240 min: 26 +/- 5 pg/ml IL-6 and 105 +/- 30 pg/ml TNF alpha; mean +/- SEM, n = 16). These data indicate that the impairment of cell responsiveness following exposure of PBMC to peritoneal dialysate is not restricted to the unused fluids, but is also observed following intra-peritoneal equilibration. Moreover, our findings suggest the presence of cytokine inhibitory factors in the peritoneal dialysate of CAPD patients which appear to accumulate in the peritoneal effluent during the CAPD cycle.
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PMID:Inhibition of cytokine synthesis by peritoneal dialysate persists throughout the CAPD cycle. 141 70

Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 micrograms/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [3H]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [3H]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [3H]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH.
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PMID:Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. 141 18

Group B streptococci (GBS) are a leading cause of sepsis and meningitis in neonates. Since cytokines are thought to play an important role in septic shock, we have studied serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in BALB/c mice infected with type III GBS. TNF alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial serum samples obtained after infection. After i.p. challenge with an LD50, serum TNF alpha rose above baseline values as early as 3 hr, peaked at 7 hr, and returned to baseline values at 20 hr. IL-6 serum levels rose concomitantly with TNF alpha, peaking 8 hr after challenge. No serum TNF alpha activity was detected in the course of sublethal infections. However, a transient rise in TNF alpha levels was observed after i.v. inoculation of high numbers (greater than or equal to 1 x 10(8) of heat-killed GBS. When groups of mice were injected i.v. with a single dose of anti-TNF alpha rabbit serum 2 hr before challenge with an LD90 or LD30, no effect was noted in terms of survival, although the serum TNF alpha peak was completely abrogated. Serum TNF alpha does not seem to play an obligatory role in GBS-induced lethality of adult mice. However, further studies are needed to assess better the role of this cytokine in the pathogenesis of GBS sepsis.
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PMID:Production of tumor necrosis factor-alpha and interleukin-6 in mice infected with group B streptococci. 142 22


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