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)

Our study was designed to investigate the production of interleukin-1 (IL-1) and IL-6 in tumor-associated macrophages (TAM) isolated from ascites (18 cases) or solid (7 cases) human ovarian carcinoma. These are pleiotropic monokines which, in addition to affecting proliferation and differentiation of lymphocytes, act on various targets, including vascular cells and liver, and may therefore be involved in the pathogenesis of certain manifestations of malignancy. IL-1 was measured by the thymocyte co-stimulator assay, under conditions in which IL-6 was inactive, and, in 8 cases, by radioimmunoassay (RIA). IL-6 was measured as hybridoma growth factor (HGF) on the 7TD1 cell line. TAM did not release appreciable levels of IL-1 spontaneously and, upon LPS stimulation, were poor producers of this monokine compared to blood monocytes. In contrast, TAM supernatants contained a high level of HGF in the absence of deliberate stimulation, and exposure to LPS either did not affect or further augmented production of this monokine. HGF activity of TAM supernatants was completely blocked by anti-IL-6 antibodies. Ascites fluid from 8 ovarian-carcinoma patients contained high levels of HGF activity, blocked by anti-IL-6 antibodies. Thus, TAM exhibit a dissociation in their capacity to release the functionally related monokines IL-1 and IL-6. IL-6 produced by TAM may account for the elevation of liver-derived acute-phase proteins associated with malignancy.
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PMID:IL-1 and IL-6 release by tumor-associated macrophages from human ovarian carcinoma. 258 59

Although fibroblasts are important in providing a structural framework for most tissues, they also appear to be active participants in the inflammatory process via the production of specific mediators. The production of inflammatory mediators by fibroblasts is especially important in relation to their strategic location within connective tissue as they may act as a cellular communication bridge between the interstitium and vasculature. In this paper, we demonstrate that fibroblasts may participate in these inflammatory reactions by the production of a neutrophil chemotactic factor (NCF) with characteristics similar to a recently isolated and cloned monocyte-derived NCF. Either tumor necrosis factor-alpha-, interleukin-1 alpha-, or interleukin-1 beta-stimulated fibroblasts showed both a time- and dose-dependent increase in steady-state levels of NCF mRNA and secretion of chemotactic activity. In contrast, lipopolysaccharide and interleukin-6 failed to induce fibroblast-derived NCF. The expression of fibroblast-derived NCF mRNA was first detectable by 30 min poststimulation, whereas chemotactic activity was significantly observed 3-4 h postchallenge. Heat-inactivated monokine (100 degrees C) failed to induce NCF mRNA expression, suggesting that only the active proteins are capable of inducing NCF. Gel filtration analysis using high pressure liquid chromatography indicated peak chemotactic activity with an approximate molecular mass of 8000 daltons. This peak of NCF activity was found to be relatively stable to both heat and trypsin inactivation. Specificity of the fibroblast-derived neutrophil chemotactic activity was demonstrated with inhibition of chemotaxis by the addition of neutralizing antibody directed against recombinant human neutrophil chemotactic factor. These data provide evidence that monokine-treated fibroblasts can synthesize a potent chemotactic agent with molecular and physicochemical characteristics similar to monocyte-derived NCF and that this factor may contribute to neutrophil-mediated disease processes.
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PMID:Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. 265 89

The vascular endothelium plays an important role in fibrinolysis by producing tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). The monokine tumor necrosis factor (human recombinant TNF) increased the production of PAI by cultured human endothelial cells from umbilical vein (twofold) and from foreskin microvessles (four to eight fold). This was demonstrated by titration of endothelial cell-conditioned medium with t-PA, by reverse fibrin autography, and by immunoprecipitation of [35S]PAI-1 by anti-PAI-1 IgG. TNF also induced a marked increase of PAI-1 messenger RNA (mRNA) in the cells. The stimulation of PAI activity by TNF was seen at 4 U/mL and reached a maximum at 500 U/mL. Human recombinant lymphotoxin and interleukin-1 (alpha and beta) also stimulated the production of PAI activity, while interleukin-6 was ineffective. Separate additions of TNF or interleukin-1 (IL-1) at optimal concentrations (500 U/mL and 5 U/mL, respectively) resulted in a comparable stimulation of PAI production by endothelial cells. The simultaneous addition of both mediators resulted in an additive effect. The effect of TNF could not be prevented by the addition of polymyxin B or by anti-IL-1 antibodies. Therefore, it is unlikely that TNF acts through the induction of IL-1 secretion by endothelial cells. Two hours after a bolus injection of 250,000 U/kg TNF into rats, a fivefold increase in circulating PAI levels was found. In the next ten hours, the levels returned to normal. Blood platelets do not significantly contribute to the increase in circulating PAI, because the number of platelets did not change after TNF injection and the amount of PAI in blood platelets is not sufficient for several hours during an increase in PAI activity. The acute phase reactants, fibrinogen and alpha 2-antiplasmin in rat plasma, were altered little if any two to 24 hours after injection of 250,000 U/kg TNF. In vitro, TNF did not change PAI production by human and rat hepatocytes in primary monolayer culture. Therefore, it is most likely that vascular endothelial cells contribute to the increased amount of circulating PAI induced by TNF in vivo. This increase in PAI activity might decrease fibrinolysis.
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PMID:Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo. 314 Sep 9

Interleukin-6 (IL-6) is a monokine with a number of biological activities, which are intimately related to inflammatory responses. We have measured IL-6 levels in synovial fluid (SF) and serum (Se) of patients with rheumatic diseases. SF-IL-6 levels were a thousand-fold higher than corresponding Se levels and a positive correlation was found between SF and Se levels suggesting that Se-IL-6 is derived from IL-6 produced in the joint. Se levels of IL-6 were also positively correlated to C-reactive protein (CRP) levels, supporting the in vitro experiments showing that IL-6 stimulates hepatocytes to produce CRP. Finally we observed a positive correlation between SF-IL-6 levels and the local activity score.
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PMID:Interleukin-6 (IL-6) in synovial fluid and serum of patients with rheumatic diseases. 326 31

We have investigated the interaction of soluble peptidoglycan (sPG), in comparison with lipopolysaccharide (LPS), with human mononuclear cells (MNC) by determining the capacity of sPG to induce interleukin-6 (IL-6) and IL-1 release. In addition, we investigated the modulation of their interaction by anti-CD14 monoclonal antibody and by partial structures of LPS. We found that sPG, like LPS, was able to induce IL-6 and IL-1 production by MNC. However, dose-response experiments revealed that at least 3,000 ng of sPG per ml was necessary for induction, whereas the optimal LPS concentration was 1 ng/ml. Anti-CD14 monoclonal antibody reduced sPG- and LPS-induced IL-6 and IL-1 production. Moreover, partial structures of LPS were able to reduce monokine production induced by sPG and LPS. We conclude that sPG constitutes, like LPS, an inflammatory cytokine inducer and that CD14 is involved in the activation of human monocytes not only by LPS but also by sPG.
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PMID:Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures. 752 97

Glycosphingolipids (GSL) isolated from the gram-negative lipopolysaccharide (LPS)-free bacterium Sphingomonas paucimobilis have remarkable structural similarities with LPS and its hydrophobic part, termed lipid A. Like LPS, but in contrast to the structurally related ceramides and cerebrosides, GSL contain an alpha-linked, negatively charged pyranosidic glycosyl component adjacent to the lipid portion and are capable of forming membranes. Because of these similarities, it was of interest to investigate whether these GSL are also able to induce monokine production in human mononuclear cells (MNC). Our results show that a GSL containing four sugar residues (GSL-4A) induced the release of tumor necrosis factor, interleukin-6, and interleukin-1 in MNC, whereas GSL-1, containing only one glycosyl residue, was inactive. A minimal concentration of 1 microgram of GSL-4A per ml was necessary to induce monokine production in MNC, whereas LPS was as active at a 10,000-fold-lower concentration (0.1 ng/ml). Both GSL-4A-induced monokine production and LPS-induced monokine production were reduced by the bactericidal/permeability-increasing protein and GSL-1. In contrast to LPS, GSL-4A-induced monokine release could be inhibited neither by an anti-CD14 monoclonal antibody nor by lipid A partial structures. We therefore conclude that at the receptor level, different mechanisms are involved in the LPS- and GSL-4A-induced monokine release.
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PMID:Glycosphingolipids from Sphingomonas paucimobilis induce monokine production in human mononuclear cells. 754 35

Using our scoring system, we studied the production of monokines (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6) by lipopolysaccharide-stimulated peripheral whole blood in 34 patients with chronic hepatitis C during the interferon-alpha/beta therapy. It decreased in 25.7% (9/35 group A), fluctuated in 60.0% (21/35, group B), and increased in 14.3% (5/35, group C). The patients in group A were younger than those in group B (P < 0.05). The histological grade of injury was milder in group A than in group B or C. The rate of sustained response was 66.7% (6/9) in group A, 19.0% (4/21) in group B, and 40.0% (2/5) in group C(P = 0.0184, group A versus group B). In summary, monokine production by peripheral whole blood varied during interferon therapy for chronic hepatitis C patients. No significant change was noted in 60% of the patients. However, patients with decreased monokine production were younger, with a mild histological grade, and likely to respond to the interferon therapy.
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PMID:Monokine production by peripheral whole blood in chronic hepatitis C patients treated with interferon. 758 25

Ozone (O3) is one of the major irritant oxidant gases in photochemical smog. In the present study, the in vitro effect of low concentrations of O3 (0.1 to 1 ppm) was evaluated on cell viability and cytokine secretion by alveolar macrophages (AM) from guinea pigs and healthy subjects. Cell injury was estimated immediately after O3 exposure by evaluation of ATP cell content (measured by bioluminescence) and lactic dehydrogenase (LDH) release in the culture medium. No cytotoxic effect was found: the ATP cell content of both guinea pig AM and human AM did not significantly change after O3 exposure and similarly the LDH release in the culture medium was unchanged. AM-derived cytokines (tumor necrosis factor alpha [TNF alpha], interleukin-1 beta [IL-1 beta], interleukin-6 [IL-6], and interleukin-8 [IL-8]) were evaluated in AM supernatants. O3 exposure was associated with a significant increase in cytokine secretion, with a peak value at 0.4 ppm O3. The exposure of the guinea pig AM to 0.4 ppm O3 for 60 min increased the IL-6 activity by 252 +/- 60% and TNF activity by 202 +/- 35%. The increase in monokine production by the human AM was 443 +/- 208% for TNF alpha, 484 +/- 171% for IL-1 beta, 383 +/- 147% for IL-6, and 226 +/- 45% for IL-8 after a 60-min exposure to 0.4 ppm O3. Lowest O3 concentrations (0.1 and 0.2 ppm) only increased TNF alpha secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ozone stimulates synthesis of inflammatory cytokines by alveolar macrophages in vitro. 759 38

Monocyte derived cytokines (monokines) are important mediators in inflammatory diseases and cancer. Control of monokine expression is also a major therapeutic target in autoimmune inflammation. Whole blood cultures permit examination of monokine expression under conditions which emulate the in-vivo environment whilst avoiding many of the artefacts associated with monocyte separation and culture. Here we describe a system for measuring interleukin-1 beta, interleukin-1 alpha, interleukin-6 and tumour necrosis factor-alpha mRNA in stimulated human whole blood ex-vivo, which can be applied to specimens from treated patients. Oligodeoxyribonucleotide probes are designed to allow standardisation of hybridisation and washing procedures. Washing and reprobing of membranes in appropriate sequence permits measurement of each monokine mRNA and mRNA for glyceraldehyde-3-phosphate dehydrogenase in only 7 ml of lipopolysaccharide-stimulated human blood. The method has been used successfully in studies of dexamethasone and methotrexate action on lipopolysaccharide stimulated IL-beta gene expression.
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PMID:A system for assessment of monokine gene expression using human whole blood. 764 69

We investigated the role of monocyte/macrophage-activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and of interferon-gamma (IFN-gamma). These levels returned to almost normal during remission. Neither interleukin-4 nor granulocyte/macrophage colony-stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). Serum concentrations of soluble CD8 and soluble interleukin-2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T-cells obtained from patients with active HLH spontaneously secreted M-CSF and IFN-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma and M-CSF at least partly from T-cells, such as CD8+ T-cells, might contribute to activation of monocytes or histiocytes, resulting in the up-regulated monokine production and haemophagocytosis in HLH.
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PMID:Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults. 794 64


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