UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To infer possible mechanisms of acute airway inflammation and mucus hypersecretion in acute severe asthma, we performed cellular and biochemical analysis on sputum from 18 adults with acute severe asthma and compared the results with results of analysis of sputum from 12 adults with cystic fibrosis (CF). We found that in subjects with asthma neutrophils made up more than 75% of sputum cells in 10 samples whereas eosinophils made up more than 75% of cells in only three samples. Fifty percent of the subjects with asthma reported that their asthma exacerbation was precipitated by a respiratory tract infection, and these subjects had a significantly higher percentage of neutrophils in their sputum (85% +/- 6% vs 57% +/- 12%, p = 0.05). In the CF samples neutrophils made up more than 95% and eosinophils less than 1% of cells in all samples analyzed. Analysis of fluid phase chemicals in asthmatic and CF sputum samples showed that despite overall lower mean values of neutrophil elastase (27 +/- 11 micrograms/ml vs 466 +/- 121 micrograms/ml, p = 0.0001) and interleukin-8 (IL-8) (55 +/- 15 ng/ml vs 186 +/- 24 ng/ml, p = 0.0001), some of the asthmatic samples had values for these variables that overlapped those in the CF samples. In addition, the asthmatic samples were distinguished by the presence of higher tryptase (10 +/- 7 U/L vs 0.9 +/- 0.9 U/L, p = 0.0001) and interleukin-6 (1166 +/- 447 ng/ml vs 186 +/- 24 ng/ml; p = 0.0001) levels and by a higher ratio of albumin to mucin-like glycoprotein (0.8 +/- 0.5 vs 0.1 +/- 0.002, p = 0.02). DNA levels were lower in the asthmatic samples (0.5 +/- 0.3 mg/ml vs 3.5 +/- 1.2 mg/ml, p = 0.05). We conclude that neutrophils predominate more frequently than eosinophils as the major inflammatory cell in sputum from patients with asthma in acute exacerbation. We speculate that this may be because respiratory tract infections are a frequent precipitant of acute asthma. In addition, the high IL-8 levels and free neutrophil elastase activity observed in asthmatic sputum suggests that IL-8 may mediate airway neutrophilia in acute asthma and that neutrophil elastase may mediate mucin glycoprotein hypersecretion in acute asthma, as has been proposed for the mucin hypersecretion in CF.
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PMID:Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. 772 65

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.
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PMID:Regulation of cytokine secretion by cystic fibrosis airway epithelial cells. 811 34

Chronic lung disease of prematurity (CLD) is a common respiratory disorder of preterm infants. At autopsy, fibroblast proliferation, and components of the extracellular matrix, including collagen and fibronectin, are markedly increased in the lungs of infants who die from CLD. Examination of broncho-alveolar fluid suggests that the persistence of neutrophils is associated with the development of CLD. In our studies, the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interleukin-6, (IL-6) and mediators which reflect neutrophil recruitment and activation, including soluble intercellular adhesion molecule, interleukin-8 (IL-8) and neutrophil elastase, were increased in lavage fluid obtained from infants who developed CLD when compared to infants who did not. Furthermore, semiquantitative reverse transcriptase-polymerase chain reaction of mRNA extracted from lavage cells suggested that luminal cells may be the source of IL-6 detected in lavage fluid but non-luminal cells may be the sources of IL-1 beta and IL-8. Fibrosis is thought to be mediated by the pro-fibrotic cytokines including transforming growth factor-beta1 (TGF-beta 1). Both active and total TGF-beta 1 were increased in lavage fluid from infants who developed CLD. Furthermore, both type I procollagen and TGF-beta were increased qualitatively in lung tissue obtained at autopsy from infants who died from respiratory failure. The increase in inflammatory mediators was maximal at 10 days of age. By contrast, the increase in TGF-beta 1 was maximal at 4 days of age. This suggests that the interaction between inflammation and fibrosis in CLD is complex, and that prenatal factors may be important in the pathogenesis of CLD.
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PMID:Cytokines in chronic lung disease of prematurity. 883 40

Neutrophil activation is considered to play a major role in organ dysfunction after severe trauma. Major surgery like esophagectomy also induces various host responses including neutrophil activation and it may be responsible for postoperative complications. We measured neutrophil elastase releasing capacity in 14 patients undergoing esophagectomy to evaluate perioperative changes of neutrophil activation. Elastase releasing capacity was estimated by the fMLP-induced elastase release from separated neutrophils in vitro and expressed as % increase of released elastase activity induced by 0.2 microM fMLP. Elastase releasing capacity was significantly increased from 28.6 +/- 17.7% after induction of anesthesia to 63.7 +/- 38.8% at 72 hours after induction, and decreased to 57.6 +/- 15.4% at 72 hours after induction. Elastase alpha 1-antitripsin inhibitor complex showed no significant increase during perioperative period. Interleukin-6 showed a peak level 24 hours after induction and interleukin-8 was increased significantly 12 hours after induction and maintained the elevated level until 72 hours postoperatively. We concluded that the neutrophil activity was increased during the perioperative period of esophagectomy and the priming of neutrophil took place during extensive surgical intervention.
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PMID:[Evaluation of neutrophil activation using elastase releasing capacity in vitro during perioperative period of esophagectomy]. 902 81

Alpha-1 proteinase inhibitor (A1-Pi) is the main serine proteinase inhibitor found in human plasma and is a potent elastase inhibitor in various tissues, including lung. A1-Pi is expressed and induced in liver during inflammatory responses but can also be produced by epithelial cells. Since hepatocyte A1-Pi production is stimulated by interleukin-6 (IL-6) and other gp130-cytokines, such as leukemia inhibitory factor (LIF) and oncostatin M (OM), we investigated the role of these cytokines in regulating A1-Pi in lung epithelial cells. We show that OM, a monocyte and T cell product, can specifically and potently induce A1-Pi production in lung-derived A549 alveolar (epithelial) cells, as well as in liver-derived HepG2 cells. Both A1-Pi protein (as detected by ELISA and Western blots) and mRNA levels were enhanced 20-fold to 30-fold in A549 cells. OM was also able to stimulate the expression of tissue inhibitor of metalloproteinase-1 in these cells. Interestingly, other members of the IL-6 family (IL-6 and LIF) had little or no effect on A549 cells, and proinflammatory cytokines, such as IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) also had no stimulatory effect on A1-Pi synthesis in A549 cells. Costimulation with IL-1 beta resulted in a decrease in A1-Pi production from OM-stimulated A549 cells. However, IL-6 production was synergistically enhanced. OM was also able to stimulate A1-Pi production from a bronchial epithelial primary cell line, whereas an intestinal epithelial cell line HT29 responded to IL-6 but not OM. These results suggest that lung levels A1-Pi could be derived not only from liver and inflammatory cells but also from epithelial cells, which can be upregulated on stimulation by OM. This may have implications for regulation of local activity of human neutrophil elastase (HNE) in such diseases as emphysema and cystic fibrosis.
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PMID:Oncostatin M, but not interleukin-6 or leukemia inhibitory factor, stimulates expression of alpha1-proteinase inhibitor in A549 human alveolar epithelial cells. 919 1

We measured circulating and sputum-sol concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase-alpha1-antiproteinase complex (NEAPC), and C-reactive protein (CRP) in an exacerbation, after antibiotic treatment, and in clinically stable patients with cystic fibrosis and chronic pulmonary infection with Pseudomonas aeruginosa. The aim was to determine the compartmental patterns of a proinflammatory and anti-inflammatory cytokine compared with other markers of inflammatory activity in cystic fibrosis. IL-6, NEAPC, CRP, and absolute neutrophil count were reduced after antibiotic treatment, p < 0.01. IL-6 and CRP concentrations were greater, p = 0.007, and p = 0.01, respectively, in a stable group of patients compared with those at the end of an exacerbation. IL-6 and CRP concentrations were related (r = 0.836, p < 0.0001), and both were greater than in matched control subjects (p < 0.001) at all times studied. Sputum-sol concentrations of IL-6 after treatment were positively related to FEV1 and FVC and inversely related to concentrations of neutrophil elastase. The separation between patients and healthy subjects, and the reduction of IL-6 after antibiotic treatment indicates it could be used as a marker of inflammation, but its relationship to other markers depends on the compartment in which it is measured.
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PMID:Circulating immunoreactive interleukin-6 in cystic fibrosis. 962 Sep 3

The potential of pentoxifylline (PTX) to modify systemic inflammatory responses and lung injury following cardiopulmonary bypass (CPB) was studied in 20 patients undergoing elective coronary artery surgery. Ten control patients were compared with ten patients who received a PTX infusion of 1 mg kg-1 h-1 during surgery. Intra-vascular pulmonary leukocyte sequestration was observed in neither group following discontinuation of CPB. Plasma elastase-alpha-1-antiprotease complex rose three-fold from baseline in both groups to peak at sternal closure. No significant plasma interleukin-1 (IL-1) response was detected. Plasma interleukin-6 (IL-6) rose in both groups from baseline to peak 4 h postoperatively. There was no correlation between plasma levels of elastase complex, IL-1 or IL-6 and impairment of postoperative oxygenation. CPB was associated with significant postoperative hypoxaemia and systemic release of neutrophil elastase and IL-6 but PTX, at the given dose, did not abrogate these responses.
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PMID:Systemic inflammatory responses to cardiopulmonary bypass: a pilot study of the effects of pentoxifylline. 972 28

The membranes tested in the present study were cellulose triacetate (CTA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN). The adsorption by each membrane of albumin, IgG, C3a, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), human neutrophil elastase (HNE), and tumor necrosis factor alpha (TNFalpha) was examined and semiquantitatively graded by confocal laser scanning fluorescence microscopy (CLSFM). After clinical use the dialyzers were treated with antibodies for these proteins and cytokines. Then the samples were incubated with fluorescein isothiocyanate-labeled anti-IgG antibody and observed by CLSFM. The changes in the blood levels of C3a and cytokines were also studied. In the CTA membrane, the adsorption of these substances, except for albumin and HNE, was less than in the synthetic membranes. The PAN membrane revealed the most abundant adsorption, especially for IL-1beta, IL-6, and TNFalpha. Although a marked elevation of C3a in the blood was observed in the CTA membrane, considerable adsorption was evident in the PMMA and the PAN membranes. Because the changes in the blood levels could be affected by membrane adsorption, both the blood levels and the adsorption of the biocompatibility parameters should be evaluated when membrane biocompatibility is discussed.
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PMID:Adsorption of complement, cytokines, and proteins by different dialysis membrane materials: evaluation by confocal laser scanning fluorescence microscopy. 987 92

Inflammatory phenomena at sites of atherosclerotic plaques are increasingly thought to be major determinants of the progression and clinical outcome of atherosclerotic disease. Therefore, attention is being paid to systemic markers/mediators which may reflect the inflammatory activity in the plaques. This study evaluates the pattern of the main proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), their soluble receptors/antagonist, and a variety of inflammatory markers, in patients with peripheral arterial disease (PAD). Eight patients with PAD suffering from claudicatio intermittens (CI), eight with critical limb ischemia (CLI) and eight controls (C) were studied. Blood samples were collected at baseline in all groups and. for C and CI, immediately after and 4 h after a 30-min treadmill test. Baseline: no differences in cytokine plasma levels were detected among the three groups. In contrast, soluble receptors of TNF (type I and II) and of IL-6, and IL-1beta receptor antagonist (IL-1ra) were increased in CI and CLI patients, as compared to C. Of note, IL-Ira correlated with the occurrence and stage of the disease in a highly significant proportion of the patients, reaching a predictive value for the disease of P < 0.0001. The opposite trend was observed for the soluble receptor of IL-1beta. Notably, in the patients no alterations could be found in white blood cell counts, expression of CD11c adherence molecule by circulating monocytes or, in vitro. O2- release from zymosan-activated neutrophils. Moreover, plasma levels of platelet activating factor (PAF), of neutrophil elastase and of the acute phase reactants C-reactive protein (CRP) and alpha1-acid glycoprotein were not found to be significantly altered. In contrast, the acute-phase proteins alpha1-antitrypsin (alpha1AT) and haptoglobin (HG) were found to be increased. Effect of treadmill: IL-1beta and TNFalpha remained at baseline levels following exercise, and IL-6 dropped to undetectable levels. Among cytokine antagonists, again the most relevant changes concerned the IL-1ra, which was significantly increased immediately after the treadmill test, both in CI and C, and returned to baseline levels after 4 h. In contrast, soluble TNFalpha, IL-1beta and IL-6 receptors, PAF, and the other markers of leukocyte activation were not found to be altered. Soluble TNFalpha and IL-6 receptors were shown to inhibit the biological effects of their ligands. Similarly, IL-1ra and the acute phase proteins alpha1AT and HG have been reported to exert anti-inflammatory functions. The increased plasma levels of these agents, together with low levels of inflammatory cytokines and other pro-inflammatory mediators such as PAF and alpha1-acid glycoprotein, appear to draw an undescribed picture, so far, of upregulation of a composite systemic anti-inflammatory mechanism in atherosclerotic patients. IL-1ra appears to be a reliable marker of the state of activation of this mechanism. These results may provide a basis for developing new insights into the pathogenesis of the atherosclerotic disease.
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PMID:Atherosclerosis and inflammation. Patterns of cytokine regulation in patients with peripheral arterial disease. 1042 95

Intestinal inflammatory disease or infection often results in the loss of the epithelial layer as a result mainly of the action of proteases, including the leucocyte serine proteinases (neutrophil elastase), lysosomal cathepsins and the matrix metalloproteinases from recruited inflammatory cells. Previous studies have shown that bronchial or intestinal epithelial cells (IEC) can respond to proteolytic attack by producing cytokines. In this study, we have determined the effect of protease treatment on interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production by IEC lines. Both neutrophil elastase and trypsin treatment induced elevated levels of mRNA for IL-6 in rat IEC-6 cells. Non-proteolytic detachment of the IEC-6 cells also induced elevated levels of IL-6 mRNA, suggesting that the effect was not caused by a specific protease or degradation product, but probably by an effect on cell shape or cell detachment. Similar results were seen with the IEC-18 cell line. Trypsin treatment of the IEC-6 cells also enhanced unstimulated and IL-1 beta costimulated IL-6 secretion, but not MCP-1 secretion or mRNA levels. Finally, nuclear levels of the CCAAT/enhancer binding protein-beta (C/EBP-beta) were rapidly enhanced after proteolytic detachment of the IEC-6 cells, suggesting a mechanism for the enhancement of IL-6 mRNA responses. These data indicate that epithelial cells can respond to proteolytic attack or cell detachment by producing IL-6, a cytokine with several anti-inflammatory and antiprotease effects, which may be important in moderating the loss of the epithelial layer by its effects on nearby epithelial or inflammatory cells.
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PMID:Epithelial cells respond to proteolytic and non-proteolytic detachment by enhancing interleukin-6 responses. 1184 20

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