UNIPROT:P05231 - FACTA Search

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)

Sudden unexpected nocturnal deaths (SUND) occur in young immigrant workers, mainly from south-east Asia, who are employed in countries such as Singapore and Saudi Arabia. Pyrogenic toxins of Staphylococcus aureus have been identified in two cases of sudden unexpected death in adults in the UK and it has been suggested that these or other toxins with superantigen properties might induce strong inflammatory responses leading to sudden unexpected nocturnal deaths. The objectives of the present study were (1) to assess the levels of antibodies to pyrogenic staphylococcal toxins in the general population, (2) to assess the levels of IgG to the toxins needed to reduce the production of inflammatory mediators by 50% in a model system, (3) to assess in a model system the effects on inflammatory responses to toxic shock syndrome toxin-1 (TSST) of cortisol levels present at night, during the day and under conditions of physiological stress. Enzyme linked immunosorbent assays were used to assess levels of IgG to TSST, staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin C (SEC). Human buffy coats were used to examine the effect of IgG to the toxins for neutralising activity and the effect of cortisol on induction of inflammatory mediators. Tumour necrosis factor alpha (TNF-alpha) was detected by a bioassay with L929 cells, interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured by an enzyme linked immunosorbent assay. IL-6 and TNF-alpha levels elicited by the toxins were not reduced by night time levels of cortisol (5-10 microg dl(-1)) levels. Day time levels of cortisol (10-20 microg dl(-1)) significantly inhibited IL-6 production but not TNF-alpha in responses. Stress levels of cortisol (40 80 microg dl(-1)) significantly reduced all three cytokines earlier than the normal day time levels. The majority of the population tested had sufficient antibodies to reduce TNF-alpha and IL-6 responses elicited by TSST and SEC in the model system. In the age range in which most sudden unexpected nocturnal death cases occur (20-39 years), males had significantly lower levels of IgG to TSST compared with females. If these toxins play a role in precipitating the series of events leading to sudden unexpected nocturnal death, the higher levels of IgG to the toxins observed in females might explain partly the much higher prevalence of these deaths among men in this age range. If inflammatory responses play a role in sudden unexpected nocturnal death, the inability of the night time levels of cortisol to control IL-6 and TNF-alpha in the model system might reflect these interactions in vivo. The methods developed for detection of the toxins in tissue samples and the quantitative IgG assays for anti-toxins can be applied to investigation of SUND victims to test the hypothesis that some of these deaths are precipitated by pyrogenic staphylococcal toxins.
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PMID:Pyrogenic toxins of Staphylococcus aureus in sudden unexpected nocturnal deaths in adults and older children: factors influencing the control of inflammatory responses to toxic shock syndrome toxins. 1044 10

Tumour necrosis factor-alpha (TNF-alpha), secreted by cells of the macrophage-monocyte lineage, has a well established role in inflammation and host-defence. The more recent discovery that adipocytes also secrete TNF-alpha has led to a substantial body of research implicating this molecule in the insulin resistance of obesity. However, little is known about the normal regulation of TNF-alpha release from human adipose tissue. In particular, it is not known whether adipocyte production of TNF-alpha is responsive to similar or different molecular regulators than those relevant to macrophages. TNF-alpha release from cultured human adipose tissue and isolated adipocytes was examined using an ELISA. Insulin, cortisol or the thiazolidinedione, BRL 49653, did not have a significant effect on TNF-alpha release from adipose tissue or isolated adipocytes. In contrast, lipopolysaccharide (LPS), a major stimulus of TNF-alpha protein production in monocytes and macrophages, resulted in a fivefold stimulation of TNF-alpha release from human adipose tissue. Significant stimulation of TNF-alpha release was also seen from isolated adipocytes, indicating that the increase in TNF-alpha release from adipose tissue in the presence of LPS is unlikely to be entirely attributable to contaminating monocytes or macrophages. Consistent with this observation was the finding that mRNA for CD14, a known cellular receptor for LPS, is expressed in human adipocytes. The increase in TNF-alpha protein release in response to LPS was blocked by an inhibitor of the matrix metalloproteinase responsible for the cleavage of the membrane-bound proform of TNF-alpha, indicating that this release represented regulated secretion and was not due to cell lysis. In conclusion, the regulation of TNF-alpha protein release from human adipose tissue and isolated adipocytes appears to be similar to its regulation in cell types more traditionally implicated in host defence. The production by the adipocyte of a range of molecules involved in host defence-TNF-alpha, factors D, B and C3, interleukin-6, and macrophage colony-stimulating factor--suggest that this cell type may make a significant contribution to innate immunity.
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PMID:Regulation of tumour necrosis factor-alpha release from human adipose tissue in vitro. 1049 4

The serum concentrations of inflammatory (Interleukin-1 beta, Tumor necrosis alpha, Interleukin-6) and regulatory cytokines (Interleukin twelve) have been studied in ten AIDS cachectic patients and compared to a control group. A cytokine imbalance, and peculiarly a significant increase in proinflammatory cytokines (Interleukin-1, Interleukin-6, Tumor necrosis Factor alpha) and a decrease in regulatory cytokines such as Interleukin-12 were found. A significant correlation resulted between weight loss and Interleukin-1 beta and 6. A negative correlation between Interleukin-1 and 12 was noted, indicating that this last cytokine has an important regulatory role also in advanced state of the disease.
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PMID:Proinflammatory and regulatory cytokine levels in AIDS cachexia. 1075 44

Segments of human temporal artery were incubated in organ culture for 2 days in the absence or presence of cytokines. Thereafter, contractions were induced by the selective endothelin ET(B) receptor agonist sarafotoxin S6c, a peptide that does not induce contraction in fresh human temporal artery. Interleukin-1beta was most potent in increasing the sarafotoxin-induced contraction in cultured segments. Tumour necrosis factor (TNF)-alpha increased the magnitude of contraction to a similar degree, but at a higher dose. A significant increase was also induced by interferon-gamma, but not by interleukin-6 at the concentrations used. The results suggest that endothelin ET(B) receptor-mediated contraction can be enhanced by pro-inflammatory cytokines in a concentration-dependent manner, and this may have relevance for pathophysiological conditions where inflammation and vasoactivity are important.
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PMID:Cytokine enhancement of endothelin ET(B) receptor-mediated contraction in human temporal artery. 1101 Oct 42

Tumour necrosis factor (TNF)-alpha-stimulated prostaglandin (PG) E(2)biosynthesis by amnion-derived AV3 cells is accompanied by increased prostaglandin H synthase (PGHS)-2 mRNA expression. PGHS-1 mRNA expression is unchanged. PGHS-2 promoter-reporter constructs (-891/+9 and 5' deletions thereof) were prepared. The regions containing concensus nuclear factor kappaB (NF-kappaB) elements (-447/-438 and -222/-213) did not enhance promoter activity. Elements associated with both basal and TNF-alpha-stimulated expression lie between bases -52 and -203. Site-directed mutagenesis of nuclear factor of interleukin-6 (NF-IL6) and cyclic AMP response elements (CREs) in this region reduced both basal and induced transcriptional activity of the -203/+9 construct by over 95 per cent. Electrophoretic mobility-shift assays using oligonucleotides derived from these sites demonstrated formation of specific DNA-protein complexes. Both NF-IL6 and CRE unlabelled oligonucleotides inhibited complex formation with the NF-IL6 oligonucleotide probe. Unlabelled CRE oligonucleotide also effectively inhibited formation of the complex with the CRE probe, but reduced effectiveness was observed when the NF-IL6 oligonucleotide was the competitor. Finally, unlabelled, consensus NF-kappaB oligonucleotide failed to compete for either probe. TNF-alpha treatment did not increase levels of these complexes. Thus NF-kappaB does not enhance basal or TNF-alpha-responsive PGHS-2 transcription in amnion-derived AV-3 cells. A permissive role for NF-IL6/CRE binding proteins in regulating PGHS-2 expression in these cells is indicated, but requires further clarification.
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PMID:Tumour necrosis factor-alpha regulation of prostaglandin H synthase-2 transcription is not through nuclear factor-kappaB in amnion-derived AV-3 cells. 1109 28

The aim of this study was to determine phenotypic differences when BCG invades macrophages. Bacilli prepared from the same BCG primary seed, but produced in different culture media, were analysed with respect to the ability to stimulate macrophages and the susceptibility to treatment with cytokines and nitric oxide (NO). Tumour necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) were assayed by enzyme-linked immunosorbent assay (ELISA), whereas NO levels were detected by Griess colorimetric reactions in the culture supernatant of macrophages incubated with IFN-gamma, TNF or NO and subsequently exposed to either BCG-I or BCG-S. We found that BCG-I and BCG-S bacilli showed different ability to simulate peritoneal macrophages. Similar levels of IL-6 were detected in stimulated macrophages with lysate from two BCG samples. The highest levels of TNF and IFN-gamma were observed in macrophages treated with BCG-S and BCG-I, respectively. The highest levels of NO were observed in cultures stimulated for 48 h with BCG-S. We also found a different susceptibility of the bacilli to exogenous treatment with IFN-gamma and TNF which were capable of killing 60 and 70% of both bacilli, whereas NO was capable of killing about 98 and 47% of BCG-I and BCG-S, respectively. The amount of bacilli proportionally decreased with IFN-gamma and TNF, suggesting a cytokine-related cytotoxic effect. Moreover, NO also decreased the viable number of bacilli. Interestingly, NO levels of peritoneal macrophages were significantly increased after cytokine treatment. This indicates that the treatment of macrophages with cytokines markedly reduced bacilli number and presented effects on NO production. The results obtained here emphasize the importance of adequate stimulation for guaranteeing efficient killing of bacilli. In this particular case, the IFN-gamma and TNF were involved in the activation of macrophage bactericidal activity.
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PMID:Role of cytokines and nitric oxide in the induction of tuberculostatic macrophage functions. 1121 9

The ascites hepatoma Yoshida AH-130 induces loss of body weight and tissue waste. Tumour necrosis factor alpha (TNF-alpha) plays a pivotal role in the pathogenesis of muscle wasting in this model system, but other cytokines, such as interleukin-6, may be involved. In order to verify whether a combined anticytokine treatment may synergistically counteract muscle protein degradation, tumour bearing rats were treated with pentoxyfilline (PTX, an inhibitor of TNF-alpha synthesis), or with suramin (SUR, an antiprotozoal drug blocking the peripheral action of several cytokines including IL-6 and TNF-alpha), or both the drugs, and the effects on muscle proteolytic systems were assessed. Muscle protein loss in the AH-130-bearing rats was associated with increased activity of both the ATP-ubiquitin- and the calpain- dependent proteolytic pathways (246% and 230% of controls, respectively). Both PTX and SUR, either alone or in combination, prevented the depletion of muscle mass and significantly reduced the activity of muscle proteolytic systems. In particular, treatment with SUR, either alone or with PTX, induced a decrease in enzymatic activities to values similar to those of controls. The results obtained in the present paper demonstrate that: (i) muscle depletion in this model is indeed associated with increased proteasome- and calpain-dependent proteolysis, as previously suggested by increased mRNA expression of molecules pertaining to both pathways; (ii) anticytokine treatments effectively reduce muscle protein loss by down-regulating the activity of at least two major proteolitic systems; (iii) SUR is more effective than PTX in reducing the activity of proteolytic systems, possibly because of its multiple anticytokine action.
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PMID:Anticytokine treatment prevents the increase in the activity of ATP-ubiquitin- and Ca(2+)-dependent proteolytic systems in the muscle of tumour-bearing rats. 1220 Jan 6

Tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have recently been found to have a pain-mediating function in addition to their immunological, proinflammatory function. According to the hypothesis of neurovascular inflammation in migraine, these two cytokines could contribute to migraine pain generation. We analysed IL-6 and its soluble receptors sIL-6R and sgp130 as well as TNF-alpha and its soluble receptor sTNF-RI in 27 migraine patients and eight headache-free controls. Migraine patients tended to have less sTNF-RI (794 +/- 158 pg/ml) than controls (945 +/- 137 pg/ml). No differences in cytokine concentrations were observed. If TNF-alpha plays a role in migraine physiopathology, migraine patients may lack sufficient antagonistic sTNF-RI to neutralize hyperalgesic TNF-alpha during a migraine attack.
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PMID:Decreased sTNF-RI in migraine patients? 1253 82

Respiratory syncytial virus (RSV) bronchiolitis is an important cause of severe respiratory disease in infants. This study aimed to characterise changes in pulmonary pro- and anti-inflammatory responses in infants with RSV bronchiolitis over the course of the illness. On the day of intubation (Day 1) and the day of extubation (Day X), nonbronchoscopic bronchoalveolar lavage was performed on term and preterm infants ventilated for RSV bronchiolitis and on control infants on Day 1. Tumour necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR) and interleukin (IL)-6 messenger ribonucleic acid (mRNA) and protein were measured. Twenty-four infants, born at term and 23 infants born preterm with RSV bronchiolitis and 10 controls were recruited. TNF-alpha and IL-6 mRNA and protein in infants with bronchiolitis were greater than the control group on Day 1. In preterm infants, who were ventilated for longer than term infants, TNF-alpha and IL-6 proteins decreased between Day 1 and Day X. Concentrations of sTNFRs differed between groups on Day 1, but levels did not change between Day 1 and Day X. Large amounts of tumour necrosis factor-alpha and interleukin-6 in the respiratory syncytial virus-infected lung suggest important roles for these cytokines in the pathogenesis of respiratory syncytial virus bronchiolitis. The decrease in tumour necrosis factor-alpha and interleukin-6 protein in preterm infants may reflect the prolonged clinical course seen in these infants.
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PMID:Pro- and anti-inflammatory responses in respiratory syncytial virus bronchiolitis. 1473 41

Erythropoietin (EPO), originally known for its role in stimulation of erythropoiesis, has recently been shown to have a dramatic protective effect in animal models of myocardial ischemia-reperfusion (I-R) injury. However, the precise mechanisms remain unclear. We tried to study the anti-inflammatory properties of recombinant human erythropoietin (rhEPO) using an in vivo myocardial I-R rat model, which was established by 30 min ligation of left descending coronary and 3 h reperfusion. rhEPO or saline solution was intraperitoneally injected 24 h before I-R insult. The infarct size was measured by triphenyltetrazolium chloride (TTC)-Evans blue technique. Myeloperoxidase (MPO) activity and tissue neutrophil infiltration were studied. Ultrastructural organizations were observed and semiquantitatively evaluated. Tumor necrosis-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10 concentrations of left ventricle were analyzed by enzyme-linked immunosorbance assays; intercellular adhesion molecule-1 (ICAM-1) by reverse-transcription polymerase chain reaction; and nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1) by electrophoretic mobility shift assay, respectively. We found that a single bolus injection of 5000 units/kg of rhEPO 24 h before insult remarkably reduced infarct size and neutrophil infiltration. It greatly attenuated I-R-induced NF-kappaB and AP-1 activation with decreased TNF-alpha, IL-6, and ICAM-1 production, but enhanced IL-10 production. In conclusion, the cardioprotection of EPO may be due in part to the suppression of the inflammatory response via down-regulation of NF-kappaB and AP-1 induced by I-R. IL-10 was also suggested to play a protective role through another independent mechanism involved in cardioprotection of rhEPO.
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PMID:Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion. 1633 78

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