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)

Recent research indicates that the proopiomelanocortin derivative alpha-melanocyte stimulating hormone (alpha-MSH) is a significant modulator of host reactions including fever and inflammation. Although the precise mechanism of action is still unknown, cytokine antagonism is believed to be responsible for at least a part of its anti-inflammatory/antipyretic influence: alpha-MSH antagonizes pyrogenic and proinflammatory effects of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and interferon gamma (IFN gamma). Although it is clear that the peptide can act within the brain to inhibit fever and peripheral inflammation, an anti-inflammatory effect on a peripheral target was evidenced in animals with transection of the spinal cord. Recent data show that alpha-MSH is significant also in human disorders such as AIDS, rheumatoid arthritis, and myocardial infarction. This molecule is believed to be a key factor in neuroimmunomodulation and it may be useful as a therapeutic agent in control of inflammatory reactions.
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PMID:The neuropeptide alpha-melanocyte-stimulating hormone: a key component of neuroimmunomodulation. 748 26

We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin-6, as well as acute phase reactants alpha-1-antitrypsin and C-reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF-alpha), neopterin, interleukin 2-receptor and granulocyte-macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin-2 and interleukin-1 levels. In addition, interleukin-6, TNF-alpha and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.
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PMID:Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid. 751 36

Recently, several lines of evidence have suggested the possible of immunological dysfunction in the pathogenesis of schizophrenia. We therefore investigated the ability to produce interferons and lymphokines in response to mitogenic or viral stimulation in a whole blood assay of 37 schizophrenic patients (DSM-III-R) and of 42 healthy blood donors. Phytohaemagglutinin (PHA) was used for the induction of interleukin-2 (IL-2), interferon gamma (INF gamma), interleukin-6 (IL-6) and the soluble interleukin-2 receptor (sIL-2R) and Newcastle Disease Virus (NDV) for the induction of interferon alpha 2 (INF alpha 2). All lymphokines and, in addition, the sIL-2R in the sera were determined by ELISA technique. The psychopathological status of the patients was assessed by psychiatrists according to internationally accepted standards. The patient group showed a trend to lower levels of the interferons alpha 2 and gamma and a significant decrease of IL-2 production. The sIL-2R levels were significantly increased in the sera of schizophrenic patients. The latter increase was associated with a poor assessment of prognosis (Strauss and Carpenter). This association appears to be of interest. However, its significance is not understood, since longitudinal studies could not be performed.
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PMID:Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia. 754 76

Lymphokines play an important role in immune responses to viruses by modulating functions of T lymphocytes. In the present study, we examined the effects of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7 (IL-7), and interferon gamma (IFN gamma) on proliferation, cytotoxic activity and lymphokine production of a dengue virus-specific CD8+ human cytotoxic T lymphocyte (CTL) clone. IL-2 and IL-7 induced proliferation of the CD8+ CTL clone in the presence or absence of specific antigen, while IFN gamma suppressed proliferation of the clone. IL-7 and IFN gamma augmented dengue virus-specific cytotoxic activity without inducing non-specific cytotoxic activity, and IL-2 induced non-specific cytotoxic activity. IL-2 induced IFN gamma production by the CD8+ CTL clone. IL-4 and IL-6 did not modulate the functions of the CD8+ CTL clone in these experimental conditions. These results suggest that functions of dengue virus-specific CD8+ CTL are modulated by IL-2, IL-7 and IFN gamma, and that IL-7 is a lymphokine useful to induce growth and to maintain specific cytotoxic activity of CD8+ CTL clones in vitro.
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PMID:Modulation of the functions of dengue virus-specific human CD8+ cytotoxic T cell clone by IL-2, IL-7 and IFN gamma. 762 98

Graft-versus-host disease (GVHD) is one of the major complications which should be resolved to improve the survival rates in allogeneic bone marrow transplantation (BMT). Recently, several cytokines have been identified, suggesting that they form a cytokine network and play an important role in immune system and hematopoiesis. Among several cytokines, it has been reported that tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are mainly involved in GVHD. In the present report, we analyzed the role of cytokines in GVHD. When we measured serum cytokine levels, IL-6, interferon gamma (IFN gamma), and TNF alpha levels were increased prior to the onset of acute GVHD. For chronic GVHD, a similar pattern of cytokine increment was observed. Interestingly, these cytokines appeared to interact synergistically to induce clinical GVHD, suggesting that none of those cytokines does not function solely. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that increased IL-1 beta mRNA expression was also observed in acute GVHD in addition to increased IL-6 and TNF alpha mRNA expressions. Unexpectedly, no increased IL-2 levels were observed in both assays. In hyperacute GVHD, only IL-6 level was increased. However, in vivo administration of IL-6 into allogeneic bone marrow chimeras did not induce severe GVHD. Therefore, some other factors also appeared to be involved in inducing hyperacute GVHD. Furthermore, it is important to consider the role of inhibitory cytokines such as transforming growth factor beta (TGF beta) or IL-10.
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PMID:Cytokines involved in graft-versus-host disease. 770 47

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

Administering or neutralizing a single cytokine is currently considered to represent a promising approach to therapeutic intervention in the immune network in autoimmune diseases. In this article, evidence from animal model experiments is reviewed: intervention in such models can have results opposite to those in the clinical disease; and intended neutralization of a cytokine by the administration of anticytokine antibodies can enhance as well as block in vivo cytokine activity. In experimental autoimmune encephalitis in mice, a model system for multiple sclerosis, administration of interferon gamma (IFN-gamma) was found to reduce disease severity and, concordantly, administration of anti-IFN-gamma antibodies was found to aggravate disease. These experimental data are, however, in sharp contrast to the reports on clinical trials, in which IFN-gamma administration was followed by disease relapses. Administration of a neutralizing anti-interleukin-6 (IL-6) antibody to mice to block in vivo activity of IL-6 resulted in increased rather than decreased serum titers, an effect that was found to be due to formation of immune complexes whose elimination from the body is retarded.
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PMID:Interferons in multiple sclerosis: warnings from experiences. 778 13

Hyperacute graft-versus-host disease (GVHD), which progresses severely and rapidly, was observed in three patients with acute leukemia transplanted with bone marrow cells from human leukocyte antigens (HLA)-identical and mixed leukocyte reactions (MLR)-negative siblings. Hyperacute GVHD developed in these patients within 7 days after bone marrow transplantation (BMT) and was rapidly aggravated inspite of cyclosporin A (CyA) and short-term methotrexate (MTX) prophylaxis and treatment with bolus methylprednisolone (mPSL). These patients showed markedly increased serum interleukin-6 (IL-6) levels after BMT, whereas other cytokines such as interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), and IL-2 were not increased compared with pretreatment levels. These findings suggest that markedly increased IL-6 levels may be related to hyperacute GVHD.
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PMID:Hyperacute graft-versus-host disease accompanied by increased serum interleukin-6 levels. 791 41

Mammary gland factor (MGF) is a transcription factor discovered initially in the mammary epithelial cells of lactating animals. It confers the lactogenic hormone response to the milk protein genes. We reported recently the isolation of the cDNA encoding MGF. MGF is a novel member of the cytokine-regulated transcription factor gene family. Members of this gene family mediate interferon alpha/beta and interferon gamma induction of gene transcription, as well as the response to epidermal growth factor and interleukin-6, and have been named signal transducers and activators of transcription (Stat). The name Stat5 has been assigned to MGF. We studied the mechanisms involved in the prolactin activation of Stat5 in COS cells co-transfected with cDNA encoding Stat5 and the prolactin receptor. Prolactin treatment of the transfected cells caused activation of Stat5 within 5-10 min. This activation does not require ongoing protein synthesis. Tyrosine kinase inhibitors prevent Stat5 activation in transfected COS cells. Treatment of recombinant Stat5 with a tyrosine-specific protein phosphatase in vitro abolishes its DNA binding activity. Prolactin stimulation of transfected cells induces Stat5 phosphorylation on tyrosine. Phosphorylation of in vitro transcribed and translated Stat5 with the Jak2 tyrosine kinase, but not with fyn, lyn or lck, confers DNA binding activity. The prolactin response of the beta-casein milk protein gene promoter can be observed in COS cells transfected with cDNA vectors encoding Stat5 and the long form of the prolactin receptor. The short form of the prolactin receptor is unable to promote Stat5 phosphorylation and confer transcriptional induction in COS cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. 792 80

Rejection continues to be a major cause of graft loss in small intestine transplantation (SIT). We have studied, by semiquantitative reverse transcriptase PCR (rtPCR), the intragraft expression of cytokines relevant to rejection in a rat model. Heterotopic SIT grafts were performed from Lewis x Brown Norway F1 donors into Lewis recipients. The isograft control was Lewis into Lewis. Five animals in each isograft and allograft group were sacrificed on POD 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was isolated from portions of the terminal ileum and rtPCR performed to amplify message for interleukin-2 (IL-2), IL-2 receptor (IL-2R), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). Semiquantitative analysis was performed using 32P radionuclide incorporation and scintillation counting. The results were expressed as percent activity compared with beta-actin. Histologic correlation with cytokine expression was made. On POD 3 after SIT there was no evidence of rejection by histology and all cytokines studied showed no difference between the isograft and the allograft. On POD 5 the first evidence of mild rejection was seen on histology and IL-6, IFN-gamma, TNF-alpha showed a significant up regulation in the allograft that persisted through POD 14. mRNA for IL-2 was not significantly upregulated until POD 7 and persisted until POD 14. IL-2R was constitutively expressed in both isograft and allograft and was not a reliable predictor of rejection. Histologic rejection was moderately severe by POD 7 and severe between POD 8 and 14 correlating with the increasing expression of IL-6, IFN-gamma, and TNF-alpha. In summary, we have shown that increasing expression of mRNA for IL-6, IFN-gamma, and TNF-alpha not only correlated with severity of rejection but that upregulation began early when histologic evidence of rejection first occurred.
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PMID:The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation. 794 Jun 88


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