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)

Recently, the mitogenic effects of the Mycoplasma arthritidis supernatant, MAS, and the induction of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) by MAS have been described. In the present series of experiments we investigated human peripheral blood mononuclear cells (PBM) and human spleen cells with respect to their production of these and other cytokines. In human spleen cell cultures and PBM, MAS induced the synthesis of interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Both interleukins were secreted faster and in higher amounts by PBM. IL-6 was also induced by MAS in PBM and human spleen cells. The amounts of IL-6 measured by ELISA were higher in PBM, whereas the biological activity of IL-6 was higher in spleen cell cultures. T-cell products such as IL-2, IL-4, and IFN-gamma were also induced by MAS in PBM and spleen cells. The kinetics of IFN-gamma and IL-4 induction were negatively correlated. In PBM we found low levels of IL-4 and high IFN-gamma induction, whereas in spleen cells high titers of IL-4 and low IFN-gamma titers were observed. Collectively, our results indicate that MAS induces different networks of cytokine interactions depending on the organ from which the cells are derived.
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PMID:Induction of cytokines in human peripheral blood and spleen cells by the Mycoplasma arthritidis-derived superantigen. 158 16

The etiology of ulcerative colitis (UC) and Crohn's disease (CD) remains enigmatic. Infiltrating intestinal macrophages are capable of producing the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). We investigated the presence of IL-6, TNF-alpha and IL-1 beta mRNA transcripts in inflammatory bowel disease (IBD), normal, and other inflammatory intestinal specimens utilizing the polymerase chain reaction (PCR). TNF-alpha mRNA levels did not very between inflammatory bowel disease and control specimens. IL-1 beta mRNA levels were highest in active UC and noninflammatory bowel disease inflammatory specimens while IL-6 mRNA levels were highest in active IBD specimens. Infiltrating T cells, macrophages, and B cells were identified as sources of IL-6 protein in inflammatory bowel disease specimens by immunofluorescent staining. IL-6 transcripts were elevated only in active inflammatory bowel disease specimens, suggesting that IL-6-mediated immune processes are ongoing in the inflammatory mucosal environment of CD and UC.
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PMID:Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. 158 85

Interleukin-1 (IL-1) and interleukin-6 (IL-6) are two cytokines involved in a variety of host inflammatory reactions. The alveolar macrophage (AM), a predominant cell source for IL-1 and IL-6, exists in a microenvironment in which there are abundant extracellular matrix (ECM) components, and it is likely that ECM may participate in the inflammatory response in the lung by modulating the effector activities of AMs. To investigate this hypothesis, we cultured rat AMs on different substrates including plastic, collagen, and airways fibroblast-derived ECM (fECM) and assessed IL-1 beta and IL-6 gene expression in these cells. Our study demonstrates that cytokine gene expression in AMs is affected by the conditions of culture. IL-1 gene expression is stimulated by adherence to plastic and exposure to endotoxin, whereas IL-6 mRNA is detectable only in the cells stimulated by endotoxin. Coating the plastic with collagen or fECM modifies cytokine gene expression. At early time points, collagen enhances gene expression. At later times (5 days), actin and cytokine gene expression are predominantly maintained in the endotoxin-stimulated cells cultured on fECM. These findings suggest an extracellular environment-directed mechanism of regulation of cytokine expression in alveolar macrophages.
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PMID:IL-1 beta and IL-6 gene expression in alveolar macrophages: modulation by extracellular matrices. 159 Apr 9

Interleukin 1 (IL-1) induces a series of metabolic and endocrine effects. Activation of the hypothalamus-pituitary-adrenal axis, inhibition of food and water intake, elevation of serum interleukin-6 (IL-6) concentration and hypoglycemia are some of the effects induced by IL-1. The purpose of this study was to compare the sensitivity of these effects following central and peripheral administration of IL-1 beta. Different doses of IL-1 beta (0.1-1000 ng/mouse) were centrally (ICV) or peripherally (IP) injected to male mice two hours prior to sacrifice. The ICV administration was more efficacious than the IP injection in elevating serum corticosterone and IL-6 concentrations, whereas no difference was evident in the IL-1 beta-induced hypoglycemia. Central IL-1 beta administration was also more potent than IP injection in inhibiting overnight food and water intake. A dose-dependent effect was evident in all these cases. In summary, our data compare effects elicited by central or peripheral administration of different doses of IL-1 beta. This comparison suggests that the IL-1 beta stimulation of serum corticosterone and IL-6 and inhibition of food and water intake are events more centrally mediated than the IL-1 beta-induced hypoglycemia.
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PMID:Evidence for a different sensitivity to various central effects of interleukin-1 beta in mice. 159 38

Although interferon-gamma has been shown to effectively prime macrophages for enhanced production of tumor necrosis factor-alpha (TNF alpha), it is reasonable to assume that other cytokines present in the extracellular environment may likewise facilitate cytokine biosynthesis. For example, interleukin-6 (IL-6) is synthesized by synovial lining macrophages and fibroblasts, and has been detected (along with TNF alpha) in rheumatoid synovial effusions. Therefore, the purpose of the present study was to determine whether IL-6 influences the production of IL-1 beta and/or TNF alpha by THP-1 macrophages. Although IL-6 treatment alone resulted in only a slight increase in TNF alpha levels, administration of IL-6 followed by Sal. minnesota LPS resulted in a synergistic potentiation of TNF alpha production by THP-1 macrophages. The priming effect of IL-6 could be reversed by boiling, or by the addition of a neutralizing polyclonal antibody against IL-6. Notably, IL-6 only weakly enhanced interleukin-1 beta production. In summary, the ability of IL-6 to potentiate TNF alpha production by THP-1 macrophages may provide insight into the regulation of the cytokine network in inflammatory diseases, such as rheumatoid arthritis.
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PMID:Interleukin-6 can prime THP-1 macrophages for enhanced production of tumor necrosis factor-alpha in response to LPS. 160 43

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and C-reactive protein (CRP) were investigated in patients with chronic liver diseases (CLD) and correlated with the type of underlying disease and various clinical and laboratory parameters. Two hundred sixty-four patients suffering from various CLD were studied; 136 cases presented with liver cirrhosis, and 128 patients were in the noncirrhotic stage of their underlying liver diseases. Serum levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and CRP were elevated in patients with CLD. Endogenous cytokine patterns in CLD were stage dependent and only marginally affected by the type of underlying disease. The cirrhotic group of CLD patients showed higher serum levels in IL-1 beta, IL-6, TNF-alpha, and CRP than did noncirrhotic cases, and these differences reached the level of statistical significance. IL-1 beta and TNF-alpha values were closely correlated but did not correlate with IL-6 levels. Elevated concentrations of cytokines represent a characteristic feature of CLD regardless of underlying disease. This and the apparent stage-dependency suggest that enhanced endogenous cytokine levels represent a consequence of liver dysfunction rather than of inflammatory disease.
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PMID:Serum levels of cytokines in chronic liver diseases. 851 60

The production of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by stimulated peripheral blood monocytes/macrophages (PBM) was assessed in patients with multiple sclerosis (MS), other neurological diseases (OND) or normal controls (NC) using enzyme-linked immunosorbent assay (ELISA). PBM obtained from acute phase of MS produced significantly higher amount of all these cytokines than those from chronic stable MS, OND or NC (TNF alpha, IL-1 alpha, IL-6: p less than 0.01, IL-1 beta: p less than 0.05). Methylprednisolone (MP) inhibited the lipopolysaccharide-induced cytokine production in a dose-dependent manner. These results suggest the possible roles of activated monocytes/macrophages in the acute exacervation of MS and suppressive effect of MP on cytokine production by activated monocytes/macrophages.
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PMID:[Cytokine production by peripheral blood monocytes/macrophages in the patients with multiple sclerosis and its suppression by methylprednisolone]. 162 50

Antigen-activated immune cells acutely release cytokines which, besides their effects on the immune system, increase hypothalamopituitary-adrenocortical (HPA) function to counteract the inflammatory process. The present study was designed to test, using in vitro paradigms, whether there exists a hypothalamic and/or a median eminence site of action, whereby different substances derived from the immune system could stimulate the CRH and/or the arginine-vasopressin (AVP) neuronal pathway. For this purpose, whole medial basal hypothalamus (containing the median eminence) were dissected from female rats and incubated in vitro with several concentrations of interleukin-1 (IL-1)beta, interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, thymosin fraction 5 (TF5) or bacterial lipopolysaccharide (LPS). After a 40-min incubation period, the amounts of CRH and AVP released into the incubation medium were measured by specific radioimmunoassays (RIAs). Additional experiments were carried out by superfusing isolated rat median eminence fragments with the different test substances; CRH and AVP released into the medium were also measured by RIAs. The results indicated that IL-1 beta (10(-11) to 10(-7) M), IL-6 (0.06 x 10(-10) to 0.4 x 10(-10) M), TNF-alpha (6 x 10(-9) to 6 x 10(-7) M) and TF5 (5-500 micrograms/ml) but not LPS (1-100 ng/ml) significantly enhanced hypothalamic CRH secretion above baseline in a concentration-related fashion. Additionally, superfusion experiments demonstrated that, among all test substances, only IL-6 possesses a direct and dose-dependent CRH-releasing activity at the median eminence level. Conversely, no preparation enhanced basal AVP release in either in vitro design.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines stimulate the CRH but not the vasopressin neuronal system: evidence for a median eminence site of interleukin-6 action. 164 Oct 72

It has previously been shown that the cytokines interleukin-1 beta and interleukin-6 (IL-1 beta and IL-6) stimulate directly the release of corticotrophin-releasing-hormone-41 from the rat hypothalamus in vitro, while IL-1 beta can also stimulate the release of somatostatin. These effects can be antagonized by drugs which block prostaglandin (PG) synthesis. PGs are also involved in the control of hypothalamic neuropeptides by other neurotransmitters. In the present study, we have characterized the production of PGs from the rat hypothalamus in vitro, and investigated the effects of IL-1 beta and IL-6, as well as the neurotransmitters norepinephrine, acetylcholine and 5-hydroxytryptamine, on the acute release of PGs, using a well-validated acute hypothalamic incubation system. The rate of release of PGs [PGE2, PGF2 alpha, 6-keto-PGF1 alpha (6KPGF1 alpha) and thromboxane B2 (TXB2) in the medium was found to stabilize after 60 min of preincubation and thereafter remain constant, with TXB2 being the predominant species. Twenty-minute incubation in the presence of human recombinant IL-1 beta or IL-6, in the dose range 1-100 U/ml, had no effect on the release of PGF2 alpha, 6KPGF1 alpha or TXB2; however, the release of PGE2 was significantly increased by both IL-1 beta and IL-6. The effect of IL-1 beta was antagonized by both indomethacin and dexamethasone. None of the other neurotransmitters tested had any effect on the release of any of the PGs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 beta and interleukin-6 specifically increase the release of prostaglandin E2 from rat hypothalamic explants in vitro. 164 Oct 74

The cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce interleukin-6 (IL-6) gene expression in astrocytes. The molecular mechanism(s) by which these cytokines activate IL-6 expression was examined by transient transfection of the human IL-6 promoter linked to the reporter gene CAT (IL-6-CAT) in primary rat astrocytes. We show that both IL-1 beta and TNF-alpha exert their effects through the IL-6 promoter to increase CAT activity, indicating that the cytokines act at the transcriptional level. Use of deletion mutants revealed that the NF-kappa B-like binding site is required for cytokine induction of IL-6 promoter activity. The correlary effects of IL-1 beta and TNF-alpha on DNA-binding proteins specific for this element were examined. Treatment of astrocytes with either cytokine leads to a rapid activation (15 min) of a nuclear protein which specifically complexes with the NF-kappa B-like binding region in the IL-6 promoter. These results suggest that TNF-alpha and IL-1 beta activate IL-6 gene expression in astrocytes by a mechanism(s) involving activation of an NF-kappa B-like protein.
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PMID:Cytokine regulation of interleukin-6 gene expression in astrocytes involves activation of an NF-kappa B-like nuclear protein. 164 98


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