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)

Spontaneous bacterial peritonitis (SBP) is associated with an important production of inflammatory mediators. However, it is unknown whether there is a relationship between the abdominal production of these mediators and the development of renal impairment, one of the most important prognostic parameters in spontaneous bacterial peritonitis. We studied 52 cirrhotic patients at diagnosis and resolution of the infection, by measuring endotoxin, tumor necrosis factor (TNF), and interleukin-6 (IL-6) levels in plasma and ascitic fluid. Thirteen patients (25%) developed renal impairment. Patients developing renal impairment showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection than patients who did not (plasma TNF-alpha: 96.0+/-38.7 vs. 39.1+/-3.6 pg/mL, P=.0209; ascitic fluid TNF-alpha: 474.5+/-118.1 vs. 160.8+/-42.7 pg/mL, P=.0173; plasma IL-6: 6,635+/-2,897 vs. 458+/-109 pg/mL, P=.0004; ascitic fluid IL-6: 182,559+/-47,328 vs. 39,250+/-10,803 pg/mL, P=.0001). Independent predictors of development of renal impairment at diagnosis were: renal failure (blood urea nitrogen > 30 mg/dL or serum creatinine > 1.5 mg/dL) (P < .001), IL-6 levels in ascitic fluid (P < .001), and mean arterial pressure (P < .05). Ten of the 13 (77%) patients who developed renal impairment died during hospitalization, but only 2 of the 39 (5%) patients who did not (P=.0001). In addition, renal failure at diagnosis of the infection was the only independent predictor of hospital mortality (P < .001). In conclusion, the inflammatory response to the infection may be an important mechanism of renal impairment and the associated mortality in SBP.
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PMID:Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: relationship with the development of renal impairment and mortality. 958 75

To define the potential role of interleukin-6 (IL-6) and its soluble receptor alpha in cartilage metabolism, we analyzed their effects on tissue inhibitor of metalloproteases (TIMP) synthesis by synoviocytes and chondrocytes. TIMP-1 production by isolated human articular synovial fibroblasts and chondrocytes, stimulated by IL-6 and/or its soluble receptor, was first assayed by specific enzyme-linked immunosorbent assay; the slight stimulatory effect of IL-6 on TIMP-1 production by both types of cells was markedly amplified by the addition of soluble receptor, the maximal secretion being observed only at 96 h. TIMP-1 mRNA expression, determined by ribonuclease protection assay, was induced by IL-6 together with its soluble receptor, but TIMP-2 and -3 mRNAs were not affected by these factors. A specific neutralizing antibody abolished the effects of the soluble receptor. Finally, supernatant from synoviocytes stimulated by IL-6 plus its soluble receptor blocked almost completely the collagenolytic activity of supernatant from IL-1-induced synoviocytes. These observations indicate that IL-6 and its soluble receptor have a protective role in the metabolism of cartilage. Given the high levels of soluble receptor in synovial fluid and the marked induction of IL-6 by IL-1 or TNF-alpha, it is likely that IL-6 and its soluble receptor are critical in controlling the catabolic effects of pro-inflammatory cytokines.
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PMID:Interleukin (IL)-6 and its soluble receptor induce TIMP-1 expression in synoviocytes and chondrocytes, and block IL-1-induced collagenolytic activity. 959

The aim of the present study was to further characterize the role of alveolar macrophages (AM) in acute human lung inflammation by evaluating their capacity to produce pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Patients with severe community-acquired pneumonia (CAP; n=12) and healthy volunteers (n=10) underwent bronchoalveolar lavage (BAL). AM were separated to high purity (>96%) using fluorescence-activated cell sorting. We determined the TNF-alpha, IL-6 and IL-8 cytokine gene expression in AM ex vivo using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Moreover, we measured in vitro unstimulated, lipopolysaccharide (LPS)- and LPS/interferon-gamma inducible TNF-alpha, IL-6 and IL-8 cytokine release and evaluated samples of BAL fluids for the same pro-inflammatory cytokines using an enzyme-linked immunosorbent assay (ELISA). We found increased TNF-alpha, IL-6 and IL-8 messenger ribonucleic acid (mRNA) levels in AM from CAP patients that were significantly elevated only for IL-8. When challenged with endotoxin in vitro, AM obtained from CAP patients showed a strongly reduced potential to release TNF-alpha and IL-6 compared to healthy controls, whereas IL-8 secretion did not differ significantly between groups. Moreover, stimulation of AM from CAP patients with LPS plus IFN-gamma augmented TNF-alpha and IL-6 cytokine release to near normal levels. Interestingly, no TNF-alpha protein was measured in BAL samples from CAP patients, whereas IL-6 and IL-8 protein levels were found to be significantly increased. Together, highly purified alveolar macrophages from community-acquired pneumonia patients show relatively low ex vivo tumour necrosis factor-alpha and interleukin-6 but not interleukin-8 messenger ribonucleic acid levels that are associated with a decreased pro-inflammatory cytokine release in vitro which, however, can be restored by concurrent interferon-gamma stimulation.
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PMID:Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. 959 98

The relationship between Mycobacterium avium complex (MAC) bacteremia and proinflammatory cytokine and human immunodeficiency virus type 1 (HIV-1) RNA levels in AIDS was investigated. During a prospective study, blood samples were drawn monthly for mycobacterial cultures. Sera were available at baseline and onset of MAC bacteremia from 20 cases and at corresponding times from 19 controls. Mean interleukin-6 (IL-6) levels were 154% greater at the time of MAC bacteremia in cases than in controls. The IL-6 levels correlated with body temperature, serum tumor necrosis factor (TNF-alpha) levels, and alkaline phosphatase levels (P < or = .004 for each). Although TNF-alpha levels tended to rise more in MAC patients than in controls, the difference was not significant. However, among both cases and controls, serum TNF-alpha levels rose significantly from baseline to the time of last sample, irrespective of MAC infection (P = .015). Bacteremia was not associated with increased serum HIV-1 RNA levels. Thus, early MAC bacteremia is associated with increases in serum IL-6 levels, while TNF-alpha levels rise over time during advanced AIDS.
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PMID:Proinflammatory cytokine and human immunodeficiency virus RNA levels during early Mycobacterium avium complex bacteremia in advanced AIDS. 960 63

Cytokines, such as tumor necrosis factor (TNF) and interleukin-6, may contribute to the anorexia and cachexia of infection, cancer, and AIDS. The present study tests the hypothesis that endotoxin alters the expression of two key fat cell proteins, leptin and beta3-adrenergic receptor (beta3-AR), through a mechanism involving TNF-alpha. Increasing doses of Escherichia coli endotoxin (lipopolysaccharide, LPS) resulted in dose-dependent elevations of plasma leptin (maximal response approximately 7-fold, half-maximal effective dose of approximately 16 microg/100 g body wt) and white fat leptin mRNA in C3/HeOUJ mice. LPS also produced a large decrease in adipose tissue beta3-AR mRNA and a parallel reduction in beta-agonist-induced activation of adenylyl cyclase. Changes in plasma leptin and beta3-AR mRNA were preceded by an approximately threefold increase in white fat TNF mRNA. TNF administration resulted in changes similar to those seen with LPS. We conclude that endotoxemia results in an induction of leptin mRNA and a decrease in beta3-AR mRNA in adipose tissue, an effect that may be mediated by alterations in TNF-alpha.
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PMID:Endotoxin-induced alteration in the expression of leptin and beta3-adrenergic receptor in adipose tissue. 961 Nov 47

Cytokines are powerful mediators of biologic responses in the CNS and may contribute to cellular injury in pathophysiologic states. In order to better understand the actions of cytokines in the intact mammalian CNS, a transgenic approach was employed that targeted the expression of different cytokines to astrocytes in mice. Fusion gene constructs consisting of a GFAP expression vector into which was inserted the DNA encoding the cytokines interleukin-6 (IL-6), IL-3, or TNF-alpha were used to generate transgenic mice. Expression of the transgene-encoded cytokines in astrocytes was confirmed at both the RNA and protein levels. Transgenic mice were subject to multilevel analysis to determine the extent of structural and functional CNS alterations. Transgenic mice exhibited distinct adult-onset, chronic-progressive neurological disorders that correlated with the level and anatomic distribution of transgene-encoded cytokine expression. The principal findings were neurodegeneration and cognitive decline due to IL-6 expression, macrophage/microglial-mediated primary demyelination with motor disease resulting from IL-3 expression, and lymphocytic meningoencephalomyelitis with paralysis induced by TNF-alpha expression. These transgenic models (1) indicate that expression of cytokines per se in the intact CNS is pathogenic, with cytokine-specific neural cell injury leading to unique functional deficits; (2) recapitulate many of the structural and functional changes seen in human inflammatory neurological disorders; (3) provide a valuable tool for advancing our understanding of the CNS pathobiology of cytokines; and (4) offer a unique resource for the development and testing of therapies aimed at abrogating the harmful actions of these important mediators.
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PMID:Structural and functional impact of the transgenic expression of cytokines in the CNS. 962 40

The effects of n-6 and n-3 polyunsaturated fatty acids (PUFA) on protein metabolism, cell-mediated immunity, and production of cytokines and prostanoids were studied in experimental animals and patients with esophageal cancer. In the experimental study using a rat burn model, n-6 PUFA increased serum interleukin-6 (IL-6) and tumor necrosis factor (TNF), alpha (P < 0.05), and decreased nitrogen balance (NB) (P < 0.05), when compared with a fat-free control. But addition of n-3 PUFA reduced TNF-alpha and IL-10 (P < 0.05) and improved NB (P < 0.05). Suppressed delayed type hypersensitivity (DTH) induced by burn injury, which was not influenced by n-6 PUFA, was significantly improved by the administration of n-3 PUFA. n-6 PUFA tended to increase, and n-3 PUFA significantly decreased the endotoxin translocation. DTH, granulocyte-macrophage colony-stimulating factor, and eicosapentaenoic acid (EPA) content increased proportionately with the intravenous dose of fish oil emulsion. The effects of n-6 and n-3 PUFA were studied in the patients who underwent surgery for esophageal cancer. In the group of patients fed by total parenteral nutrition with soybean oil emulsion, the serum IL-6 significantly increased at 2 and 6 h after operation (P < 0.05). Oral/enteral supplementation of EPA ethyl ester (1.8 g/d) significantly reduced the postoperative IL-6 production (P < 0.05 at 1, 2, and 6 h after operation), and improved cell-mediated immune function 3 wk after operation (P = 0.05). During the chemoradiation therapy, cell-mediated immune function was improved significantly in the patients fed enterally with EPA ethyl ester (n = 5), when compared with the patients without EPA (n = 14).
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PMID:n-3 versus n-6 polyunsaturated fatty acids in critical illness. 964 1

In the hope of identifying agents of therapeutic value in immunoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cel proliferation in vitro. The results indicated that 7 out of the 15 crude extracts inhibited human mesangial cell proliferation activated by interleukin-1beta and interleukin-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Selaginella tamariscina (MLS-032), 56.0 +/- 2.0; Ixeris chinensis (MLS-033), 62.7 +/- 1.7; Polygonum hypoleucum Ohwi (MLS-034), 25.0 +/- 1.5; Scutellaris rivularis (MLS-036), 39.6 +/- 1.1; Condonacanthus paucifiorus (MLS-042),63.6 +/- 2.6; Xanthium strumarium (MLS-043), 42.8 +/- 1.3; Daemonoropus margaritae (MLS-044), 56.1 +/- 1.9. These findings indicate that human mesangial cells were most sensitive to MLS-034 treatment. These herbs also decreased interleukin-1beta and tumor necrosis factor-alpha production. Moreover, TNF-alpha mRNA expression was inhibited by MLS-034. It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action.
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PMID:Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies. 966 76

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.
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PMID:Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. 966 31

It has been recently hypothesized that superantigens, which stimulate T cells expressing particular T cell receptor Vbeta chain gene segments, play a precipitating or aggravating role in psoriasis. In this study, we investigated the peripheral blood mononuclear cell (PBMC) response of patients with psoriasis vulgaris to staphylococcal superantigens (staphylococcal enterotoxin A (SEA), SEB, and SEC1) and its relationship to clinical and laboratory findings. Cytokine secretion was assessed by ELISA in the supernatants of the cultured PBMCs stimulated with SEB. Results of 3H-TdR uptake showed that the PBMCs' response against SEB in patients with psoriasis vulgaris (34,468 +/- 6,455) (mean DPM SD) was significantly higher than that of normal subjects (22,756 +/- 5,780) (p < 0.005). The stimulation index (SI) of patients with psoriasis vulgaris (n = 37) (63.9 +/- 55) was significantly higher than that of normal subjects (n = 24) (26.0 +/- 23) (p < 0.005) and patients with atopic dermatitis (n = 10) (40.7 +/- 30) (p < 0.05). Similar results were obtained in response to SEA and SEC1. SI weakly correlated with the psoriasis area and severity index (PASI) score (r = 0.62) and the serum interleukin-6 (IL-6) concentration (r = 0.45). IL-2 and tumor necrosis factor (TNF-alpha) were secreted at a significantly increased level by PBMCs from psoriatic patients on incubation with SEB, after a 3 day culture period. A higher level of IL-6 was released by PBMCs stimulated with SEB in psoriatic patients than normal controls, however, the difference was not significant. These results raise the possibility that monocytes, as well as T cells, are markedly activated by staphylococcal superantigen in patients with psoriasis vulgaris, which may play a role in the triggering or aggravating of psoriasis mediated by secreted cytokines.
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PMID:Clinical analysis of staphylococcal superantigen hyper-reactive patients with psoriasis vulgaris. 968 64


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