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)

Peptide mediators, including tumor necrosis factor-alpha, interleukin 1 and interleukin-6, are associated with many chronic inflammatory diseases and septic shock. As such, considerable information has been collected by means of study of cytokine secretion from isolated cells or plasma cytokines during septic shock or inflammatory disorders. In this investigation, we used semiquantitative polymerase chain reaction analysis and a recently developed liver slice model to examine the characteristics of cytokine profiles that occur in the liver, the main organ involved in endotoxemia, after lipopolysaccharide challenge. Tumor necrosis factor-alpha, interleukin-1 alpha and interleukin-6 were rapidly secreted after in vivo LPS exposure or when added in vitro to rodent or human liver slice samples. This increase was associated with increased cytokine-specific mRNA transcripts. Kinetic analysis revealed that most tumor necrosis factor-alpha is released from the liver within 1 hr of lipopolysaccharide challenge, whereas interleukin-1 alpha and interleukin-6 continued to be produced for the entire culture period. Addition of monoclonal antibodies against tumor necrosis factor-alpha or interleukin-1 alpha to the culture partly inhibited interleukin-6 secretion, indicating that interleukin-1 alpha and tumor necrosis factor-alpha help mediate and sustain interleukin-6 synthesis. Depletion of hepatic sinusoidal macrophages (Kupffer cells) by a liposome-mediated macrophage "suicide" technique indicated that almost all of the secreted interleukin-1 alpha and tumor necrosis factor-alpha originate from these cells, whereas interleukin-6 secretion might also include other cell types. This study supports and extends previous findings and allows for a more rational approach to developing effective therapies against chronic inflammatory diseases and septic shock.
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PMID:Endotoxin-induced cytokine gene expression and excretion in the liver. 829 4

Tobacco smoke is a usual form of oxidant aggression present in the domestic environment. In the present study, the in vitro acute effects of a 2-cigarette smoke gas phase were evaluated on cell viability and cytokine secretion by alveolar macrophages (AM) from guinea pigs and human healthy subjects. Cell injury was estimated immediately after smoke exposure by evaluation of ATP cell content (measured by bioluminescence) and lactic dehydrogenase (LDH) release in the culture medium. LDH release was also measured when the interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) activities were evaluated. No cytotoxic effect was found: The ATP cell content of both guinea pig AM and human AM did not significantly change after tobacco smoke exposure. Similarly, the LDH release in the culture medium was unchanged both immediately after tobacco smoke exposure and at the time of the cytokine evaluation (18-20 h later) compared to cells cultured in the air. The total protein synthesis by the guinea pig AM evaluated by 35S-L-methionine labeling was unaffected by tobacco smoke exposure. The production of IL-6 and TNF activities was evaluated 18-20 h after smoke exposure. The IL-6 activity was measured by the proliferation test of 7TD1 hybridoma cell line; the TNF activity was evaluated by the L929 mouse fibroblast cytotoxic test and by an immunoradiometric assay (for human AM). A 2-cigarette smoke exposure decreased both activities significantly. The exposure of the guinea pig AM reduced IL-6 activity by 24.3 +/- 6.7%, 42.4 +/- 7.8%, and 39.7 +/- 9.6% and TNF activity by 33.8 +/- 10.4%, 35.1 +/- 10.7%, and 38.8 +/- 9.9% (respectively unstimulated cells and AM activated by 0.1 and 10 micrograms LPS/mL). The decrease in monokine production by the human AM was, respectively, 57.8 +/- 8.8%, 59.7 +/- 11.4%, and 49.9 +/- 10.5% of IL-6 activity and 37.4 +/- 14.6%, 17.6 +/- 9.6%, and 37.2 +/- 6.3% of TNF activity. The possible release of cytokine inhibitors was also investigated. The inhibitory activity against recombinant TNF and IL-6 was evaluated in culture medium from unstimulated AM exposed to tobacco smoke and did not significantly differ from that of AM exposed to air, demonstrating that the decrease of monokine levels could not be explained by the release of inhibitory factors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro acute effects of tobacco smoke on tumor necrosis factor alpha and interleukin-6 production by alveolar macrophages. 831 4

Constitutive and endotoxin (lipopolysaccharide [LPS])-stimulated release of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 (PGE2) by blood monocytes and peritoneal cell preparations from patients on various forms of dialysis was measured. Monocytes were obtained from healthy controls (n = 20), and from patients on peritoneal dialysis (n = 8), on hemodialysis with cellulose ester membranes (n = 9), and on hemodialysis with polysulfone membranes (n = 8). Peritoneal macrophages were recovered by lavage during laparoscopic surgery from 11 healthy controls, from dialysate in 37 patients on peritoneal dialysis, and at catheter placement for transfer to peritoneal dialysis from eight patients on hemodialysis with polysulfone membranes. Peak LPS-induced production of TNF-alpha, IL-1 beta, and IL-6 by monocytes from patients on peritoneal dialysis and cellulose ester hemodialysis was less than that by monocytes from healthy controls. In contrast, monocytes from patients treated with polysulfone hemodialysis produced amounts of cytokine not different from controls. Lipopolysaccharide-stimulated PGE2 production by monocytes was the same in both patient and control groups. Peritoneal cell preparations from patients on peritoneal dialysis showed decreased release of IL-1 beta and TNF-alpha as compared with control peritoneal cells and with their own blood monocytes. To determine whether the decreased response to LPS by peritoneal cells compared with their own blood monocytes could be attributed to lower numbers of macrophages in the peritoneal cell preparations, adherence of peritoneal cells to plastic was performed. Adherence increased the percentage of macrophages from 70% to more than 90%. In monocytes and adherence purified peritoneal macrophages from peritoneal dialysis patients, no significant difference between monocytes and adherent peritoneal macrophages could be found for TNF-alpha and PGE2. Interleukin-1 beta production by the adherent peritoneal macrophages, as by total peritoneal cells, was significantly lower than that by monocytes. Constitutive production of PGE2 and IL-6 by peritoneal cells from patients on peritoneal dialysis was significantly increased. In contrast, LPS-stimulated production of TNF-alpha, IL-1 beta, and IL-6 by blood monocytes and peritoneal cells from patients receiving hemodialysis with polysulfone membranes was comparable to that produced by monocytes and peritoneal cells obtained from healthy controls. Thus, blood monocytes and peritoneal cells from patients on peritoneal dialysis and from patients on hemodialysis with cellulose-ester membranes demonstrate a decreased cytokine response to LPS, suggesting a state similar to endotoxin tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of dialysis modality in responses of blood monocytes and peritoneal macrophages to endotoxin stimulation. 832 72

The well-known human circadian rhythm (CR) in body temperature may be due to CR in endogenous pyrogens such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF). We, therefore, investigated the daily variation in spontaneous and LPS-induced monokine release by peripheral blood cells (whole blood assay) in 10 healthy volunteers. Spontaneous release of monokines (IL-1, IL-6, TNF) showed a simultaneous significant peak at noon, whereas LPS-induced release of IL-1 and IL-6 was strictly correlated with the CR in body temperature with its significant maximum at 8.00 p.m. Since LPS-induced release of TNF showed a significant peak at 4.00 a.m., interleukins and TNF seem to be independently regulated. CR in IL-1 and IL-6 release are suggested to be responsible for the CR in body temperature.
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PMID:[Circadian rhythm in cytokines]. 834 88

We investigated the pattern of down-regulation of cytokine production in endotoxin (lipopolysaccharide [LPS]) tolerance. A 4-day treatment with LPS (35 micrograms per mouse) was followed by a challenge on day 6 with one more injection of LPS. Circulating tumor necrosis factor (TNF) and interleukin-6 (IL-6) could not be induced (> 99% inhibition) by LPS in LPS-tolerant mice; colony-stimulating factor (CSF) was also down-regulated by more than 95%, whereas interferon (IFN) and IL-1 syntheses were only partially inhibited. To study the mechanism of cytokine down-regulation in tolerance, we attempted to reverse the tolerant state by pretreatment with phorbol 12-myristate 13-acetate (PMA) (4 micrograms per mouse) 10 min before the LPS challenge. PMA completely restored IL-6 production and partially that of CSF. PMA had no effect on IFN production and inhibited the induction of IL-1. TNF production was also not restored by PMA. To investigate the role of endogenously produced cytokines in the development of LPS tolerance, we administered IL-6, TNF, or IL-1 alpha, using the same treatment schedule as that for LPS. Whereas IL-6 had no effect, IL-1 alpha or TNF induced partial tolerance to LPS in terms of inhibition of LPS-stimulated TNF and IL-6 production. However, a full LPS-tolerant state could not be induced by administration of recombinant cytokines, suggesting the existence of additional mechanisms, such as a loss of LPS receptors or changes in release of soluble binding proteins.
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PMID:Differential regulation of cytokine production in lipopolysaccharide tolerance in mice. 840 25

Interleukin-6 (IL-6) appears in the cerebrospinal fluid (CSF) of patients with acute infection of the central nervous system, and in the brains and CSF of experimental animals following systemic or intracerebral injection of bacterial endotoxin (Escherichia coli lipopolysaccharide, LPS). Since LPS is known to induce secretion of interleukin-1 (IL-1) in many cell types including those of the brain, and IL-1 can induce IL-6 in brain tissue it appeared reasonable to postulate that the effects of LPS on IL-6 production were mediated through IL-1 induction. To test this hypothesis, the effects of IL-1 receptor antagonist (IL-1Ra) on LPS and IL-1-induced IL-6 secretion were tested in a mixed brain cell culture from 17-day fetal rat, after 12-14 days in culture. IL-6 secretion was induced by IL-1 beta in a concentration as low as 1 x 10(-10) M (p = 0.0008); addition of IL-1Ra was shown to inhibit IL-1-induced changes by 87% (p = 0.0012) at a molar ratio of 100:1, and by 100% at a molar ratio of 1,000:1, LPS stimulated IL-6 secretion progressively over the concentration of 1-100 ng/ml (p = 0.0001). LPS 10 ng/ml-induced IL-6 secretion was inhibited by 66% by IL-1Ra in a concentration of 1,000 ng/ml (p = 0.0077). The inhibitory effect of IL-1Ra was not significantly greater even when used at a concentration of 5,000 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bacterial lipopolysaccharide induction of IL-6 in rat telencephalic cells is mediated in part by IL-1. 841 26

We have recently described a murine model of Staphylococcus aureus-induced septic arthritis. One of the hallmarks of this disease is a striking hypergammaglobulinemia. In the present study we have used a sensitive ELISPOT technique to assess, at the single cell level, the B-cell differentiation properties of this arthritogenic, toxic shock syndrome toxin-1 (TSST-1)-producing staphylococcal strain. In vivo, inoculation of live S. aureus resulted in lymphoproliferation, early (within 3-4 days) peak of IgM-secreting cells and late (2 weeks after the injection) pronounced increase of IgG-secreting cells. We have documented that this late increase of IgG-secreting cells is a CD4+ T-cell-dependent phenomenon. Furthermore, we have showed that there is a relationship between the hypergammaglobulinemia and the appearance of arthritis, since a nonarthritogenic staphylococcal strain will not give rise to increased frequency of immunoglobulin-secreting cells. To elucidate mechanisms responsible for S. aureus-induced polyclonal B-cell activation, we have assessed in vitro effects of formalin-fixed arthritogenic S. aureus on the release of cytokines. Our results show that the S. aureus LS-1 strain induces in vitro preferentially IgM-secreting cells, many of them displaying autoantibody properties. The magnitude of this response is high and comparable with optimal concentrations of LPS, a potent murine polyclonal B-cell activator. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor (TNF), and interleukin-6 (IL-6) were all secreted by mouse MNC after in vitro exposure to formalin-killed S. aureus. Inhibition experiments, using neutralizing antibodies to these cytokines, revealed that IL-1 alpha and IL-6 but not TNF-alpha had potent B-cell differentiation properties in S. aureus-stimulated cell cultures.
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PMID:Polyclonal B-cell activation by an arthritogenic Staphylococcus aureus strain: contribution of T-cells and monokines. 845 72

Johne's disease is a chronic enteritis of cattle and other ruminant species that is of worldwide economic importance. The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have been associated with granuloma formation and wasting in other disease syndromes. The potential role of these cytokines in the development and progression of Johne's disease has not been investigated. Using reverse transcriptase polymerase chain reaction (RT-PCR) and specific bovine oligonucleotide cytokine primers and probes for bovine TNF-alpha and IL-6, we examined the ex vivo expression of mRNA for these inflammatory cytokines in whole blood from healthy cattle. Cytokine mRNA levels increased after a brief incubation of bovine whole blood with Mycobacterium paratuberculosis or its lipoarabinomannan (LAM). Muramyl dipeptide (MDP) and Escherichia coli LPS also stimulated TNF-alpha and IL-6 mRNA expression. Several strains of M. paratuberculosis were tested and found to have similar abilities to stimulate TNF-alpha and IL-6 mRNA expression. Several strains of the closely related Mycobacterium avium, and the unrelated saprophyte, Mycobacterium phlei, had somewhat less ability to stimulate TNF-alpha and IL-6 mRNA expression.
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PMID:Ex vivo induction of TNF-alpha and IL-6 mRNA in bovine whole blood by Mycobacterium paratuberculosis and mycobacterial cell wall components. 855 37

Interleukin-6 (IL-6) is a pluripotent cytokine that may play a role in pulmonary defense against bacterial pathogens. We have quantitated the response of bovine alveolar macrophages (bAM) to bacterial lipopolysaccharide (LPS; E. coli 055: B5) in vitro using the IL-6 sensitive 7TD1 cell line. Bacteria LPS in the absence of serum induced IL-6 secretion from bAM (1 x 10(6) ml-1) over a range of LPS concentrations from 10 ng ml-1 to 10 micrograms ml-1. This resulted in IL-6 levels ranging from approximately 5 to over 200 U ml-1.IL-6 secretion by from approximately 5 to over 200 U ml-1.IL-6 secretion by LPS-stimulated bAM was increased by 24 h poststimulation, and continued to increase up to 72 h after stimulation. Fetal bovine serum (FBS, 1% vol/vol; 320 micrograms ml-1) enhanced IL-6 secretion from macrophages in the presence of LPS by approximately 10-fold compared with LPS alone. A bovine serum fraction (1 microgram ml-1 protein) prepared using ion-exchange chromatography also markedly enhanced IL-6 secretion versus LPS alone. The stimulatory effect of IL-6-like activity in the bAM supernatants was neutralized by an anti-human IL-6 polyclonal antibody. Northern blot analysis revealed increased IL-6 mRNA at 2 h poststimulation with LPS + FBS, peak levels at 4 h, and levels were decreased by 6 h poststimulation. Results suggest that IL-6 is secreted by bovine alveolar macrophages, and that bacterial LPS and serum components synergize to produce this response.
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PMID:Interleukin-6 secretion by bacterial lipopolysaccharide-stimulated bovine alveolar macrophages in vitro. 858 44

In addition to biophysical properties, pulmonary surfactant has immunomodulatory activity. We previously demonstrated that both synthetic (Exosurf) and modified natural surfactant (Survanta) downregulated endotoxin-stimulated inflammatory c ytokine mRNA levels and protein products (tumor necrosis factor-alpha [TNF], interleukin-1-beta [IL-1], interleukin-6 [IL-6]) in human alveolar macrophages. In this study, we report that both Exosurf and Survanta suppress TNF mRNA and secretion (85 +/- 4% mean percent inhibition +/- SEM by Exosurf; 71 +/- 6% by Survanta) by endotoxin-stimulated THP-1, a human monocytic cell line. Because surfactant downregulated inflammatory cytokine production similarly in both normal human alveolar macrophages and the THP-1 cell line, we used this cell line to investigate whether surfactant affected transcriptional mechanisms. Specifically, we examined nuclear factor-kappa B (NF-kappa B) activation because it is crucial in transcriptional regulation of many inflammatory cytokine genes including TNF, IL-1, and IL-6. Electrophoretic mobility shift assays showed that both surfactants decreased activation of NF-kappa B. The presence of both p65 and p50 NF-kappa B components in LPS-activated THP-1 cells was confirmed by specific antibody induction of supershifts in mobility assays. These results are the first to suggest that surfactant's suppressive effects on inflammatory cytokine production may involve transcriptional regulation through inhibition of NF-kappa B activation.
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PMID:Surfactant suppresses NF-kappa B activation in human monocytic cells. 860 Sep 42


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