Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular events that occur in status asthmaticus (SA) remain poorly investigated. Autopsy studies frequently emphasized about the presence of eosinophils in bronchial airway wall, whereas recent studies reported increased number of neutrophils in patients dying of sudden-onset fatal asthma. Mucus plugs occluding the bronchial lumen are almost constant features during SA. Bronchial lavage (BL) may be useful to remove mucus plugs in cases of atelectasis and/or refractory SA. We investigated the contribution of different cell types and cellular mediators (neutrophil elastase, eosinophil cationic protein [ECP], histamine, interleukin-8 [IL-8]) to the pathogenesis of SA. We studied 16 BL from eight patients undergoing mechanical ventilation (MV) for SA (time interval from onset of MV = Day 0 to Day 11), four BL from patients undergoing MV without preexisting respiratory disease (V), 11 BL from patients with stable asthma (A) and eight BL from healthy controls (C). SA exhibited higher number and percentage of neutrophils (81.5 +/- 4.5%) than V (44.3 +/- 12.2) (p < 0.05), A (6.9 +/- 2.7) and C (9.5 +/- 3.8) (p < 0.0001), and higher number of eosinophils than V, A, and C (p < 0.01). Neutrophil elastase, ECP, and IL-8 levels were dramatically increased in SA. Histamine was higher in SA than in C and V (p < 0.05). Bronchial neutrophilia was not related to concomitant bacterial infection as bacteriological cultures were positive in only three BL. Eosinophils, mast cells and histamine were higher in BL performed within the first 48 h of MV (p < 0.05) than in BL performed later on. Our results indicate that bronchial inflammation in SA differs from bronchial inflammation in mild asthma. Persistent bronchial neutrophilia is associated with increased eosinophils and mast cells in the early phase of SA. Neutrophils may result in tissue damage and participate to the shedding of the epithelium in SA.
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PMID:Bronchial neutrophilia in patients with noninfectious status asthmaticus. 947 49

Repeated intranasal administration of interleukin 8 (IL-8) induces bronchial hyperresponsiveness (BHR) accompanied by lower airway neutrophil accumulation (ANA) in guinea-pigs. Leukotriene B4 (LTB4) is a chemotactic factor for neutrophils. To elucidate whether LTB4 and neutrophil elastase are involved in the IL-8-induced BHR and ANA, the effects of a LTB4 antagonist (ONO-4057) and a neutrophil elastase inhibitor (ONO-5046) on the responses were examined. IL-8 (5 microg x kg[-1]) was administered intranasally to guinea-pigs twice weekly for 3 weeks. One day after the last administration, animals were anaesthetized and artificially ventilated through tracheal cannulae, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to inhaled histamine. ONO-4057 (2 or 20 mg x kg[-1]) or ONO-5046 (30 or 300 mg x kg[-1]) was administered intraperitoneally 24 and 1 h before anaesthesia. ONO-4057, but not ONO-5046, significantly inhibited the IL8-induced BHR and ANA, assessed by bronchoalveolar lavage, in a dose-dependent manner. These findings suggest that interleukin 8 causes bronchial hyperresponsiveness and airway neutrophil accumulation in guinea-pigs in vivo. In part this appears to be due to release of leukotriene B4, whereas it may not be mediated by neutrophil elastase.
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PMID:Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8. 955 29

The purpose of this study was to investigate the characteristics of pulmonary inflammation caused by Mycobacterium avium-intracellulare (MAI) in individuals with neither predisposing lung disease nor immunodeficiency. We reviewed the records of 20 patients with pulmonary MAI infection (including 19 female patients) whose past history and previous chest radiographs revealed no predisposing lung disease. We analysed the bronchoalveolar lavage fluid (BALF) from these 20 patients and from six normal female controls. The BALF was recovered directly from the relevant segment that was identified with chest-computed tomography. The BALF cell profiles showed significantly elevated counts for total cells, lymphocytes and neutrophils, but the macrophage cell count was not elevated. The CD4+ lymphocyte count and CD4+/CD8+ ratio were significantly increased compared with those in the controls. The lymphocytes demonstrated phenotypical evidence of activation, with increased expression of human leukocyte antigen-D-related antigen (HLA-DR). The tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and IL-8 concentrations were significantly increased. The neutrophil elastase concentration was also increased, and it was significantly correlated with the neutrophil cell count in the BALF. These findings suggest that the increased counts of activated CD4+ lymphocytes and neutrophils and the elevated concentrations of proinflammatory cytokines and neutrophil elastase appear to be common characteristics in Mycobacterium avium-intracellulare infection.
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PMID:Analysis of BAL fluid in M. avium-intracellulare infection in individuals without predisposing lung disease. 965 59

We examined the effect of the neutrophil chemoattractants interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine on goblet cell (GC) degranulation in guinea pigs. Chemoattractants caused time-dependent neutrophil recruitment and GC degranulation in vivo. NPC 15669 (an inhibitor of leukocyte infiltration) prevented both responses, implicating neutrophils. ICI 200,355 (an inhibitor of neutrophil elastase and proteinase-3) or secretory leukocyte protease inhibitor (an inhibitor of elastase but not of proteinase-3) abolished IL-8-induced GC degranulation, implicating elastase. Incubating tracheal segments with IL-8 plus neutrophils caused GC degranulation in vitro, an effect due to activation of the neutrophils themselves (and not an effect present in the supernatant). Chemoattractant increased surface staining of elastase and the cleavage of elastase-specific fluorogenic substrate by neutrophils. Pretreatment with anti-intercellular adhesion molecule-1, anti-CD18, or anti-CD11b antibody inhibited the chemoattractant-induced GC degranulation in vitro, implicating adhesion molecules. These studies suggest that chemoattractants cause neutrophil-dependent GC degranulation involving adhesive interactions between cells, with elastase activity occurring at the cell interface, causing GC secretion. The findings, reproduced in human airways, suggest novel methods of therapeutic intervention.
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PMID:Neutrophil-dependent goblet cell degranulation: role of membrane-bound elastase and adhesion molecules. 970 90

Platelet microparticles (PMP) were isolated from outdated platelets by a combination of differential centrifugation and gel filtration, and the concentration of PMP was expressed in the equivalent of GPIIb/IIIa complex measured by captured ELISA. PMP bound to isolated neutrophils and macrophages in a dose-dependent manner, but they did not bind to lymphocytes. Incubation of PMP with neutrophils did not activate these cells as measured by up-regulation of Mac-1, release of human granulocyte elastase, and calcium mobilization. Incubation of PMP with macrophages did not enhance IL-8 production and the oxygen burst but slightly and significantly increased production of MCP-1. After 10 min incubation of PMP with macrophages, an increase of GPIIb/IIIa antigen was observed suggesting that PMP may be endocytosed by macrophages. In conclusion, PMP bind to leukocytes, but, in contrast to activated platelets, do not play a significant role in leukocyte activation.
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PMID:Interaction of leukocytes with platelet microparticles derived from outdated platelet concentrates. 986 71

Various treatment regimens and difficulties with research design are encountered with cystic fibrosis (CF) because no standard diagnostic criteria exist for defining acute respiratory exacerbations. This study evaluated the role of serial monitoring of concentrations of selected cytokines and inflammatory mediators in serum and sputum as predictors of respiratory exacerbation, as useful outcome measures for CF, and to guide therapy. Interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), neutrophil elastase-alpha-1-protease inhibitor complex (NE complex), protein, and alpha-1-protease inhibitor (alpha-1-PI) were measured in serum and sputum collected from CF patients during respiratory exacerbations and periods of well-being. Levels of NE complex, protein, and alpha-1-PI in sputum rose during respiratory exacerbations and fell after institution of antibiotic therapy (P = 0.078, 0.001, and 0.002, respectively). Mean (+/- standard error of the mean) levels of IL-8 and TNF-alpha were extremely high in sputum (13,780 +/- 916 and 249.4 +/- 23.5 ng/liter, respectively) but did not change significantly with clinical deterioration of the patient (P > 0.23). IL-8 and TNF-alpha were generally undetectable in serum, and therefore these measures were unhelpful. Drop in forced expiratory volume in 1 s was the only clinical or laboratory parameter that was close to being a determinant of respiratory exacerbation (P = 0.055). This study provides evidence of intense immunological activity occurring continually within the lungs of adult CF patients. Measurement of cytokines and inflammatory mediators in CF sputum is not helpful for identifying acute respiratory exacerbations.
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PMID:Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis. 1006 64

During the last few years attention has been focused on an important role of inflammatory mediators in the pathophysiology and systemic complications of acute pancreatitis. The present study deals with those of the mediators which have shown demonstrable activity in the course of pancreatitis, e.g. acute-phase proteins (among others C-reactive protein and alpha-1-antitrypsin) and neutrophil elastase (PMN-elastase) as the marker for granulocyte activity. The activity of cytokines IL-6, IL-8 and IL-1, of alpha-cachectin (TNF alpha), as well as of the platelet-activating factor (PAF) and the trypsinogen activation peptide (TAP), was discussed.
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PMID:[Inflammatory mediators in the acute pancreatitis]. 1033 84

The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.
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PMID:Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection. 1044 14

The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators. Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -70 degrees C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity. In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0-153) versus 0 (0-5.6) ng x mL(-1)) HNE (136 (32-694) versus 14 (0-516) ng x mL(-1)) and elastase activity (4 (1-220) versus 1 (0-339) mU x mL(-1)) were found. These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease.
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PMID:IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis. 1048 41

There is a driving need to develop new and effective treatments for COPD. Bronchodilators are now the mainstay of symptomatic therapy and a new long-acting anticholinergic bronchodilator, tiotropium bromide, is now in advanced clinical trials as a once daily dry powder inhaler. Several inflammatory mediators are involved in the chronic neutrophilic inflammation that typifies COPD, including leukotriene B(4) and interleukin 8, for which specific receptor antagonists have been developed. Since the inflammatory process in COPD is essentially steroid resistant, new antiinflammatory treatments are needed. Drugs that may be effective include phosphodiesterase 4 inhibitors, NF-kappaB inhibitors, and interleukin 10. Inhibition of proteases is another approach and inhibitors of neutrophil elastase, cathepsins, and matrix metalloproteases are now in clinical development. Supply of endogenous antiproteases, such as alpha(1)-antitrypsin and secretory leukocyte protease inhibitors as recombinant proteins or by gene transfer, is also being explored. In future drugs that may stimulate alveolar repair might be developed, including retinoid receptor agonists and hepatic growth factor. Future directions will include earlier detection of disease, gene profiling to identify which smokers are at risk of COPD, and the development of noninvasive surrogate markers to monitor disease activity in order to monitor new therapies. Identification of genes that confer a risk for COPD in smokers may identify novel targets for drug development. Barnes PJ. Novel approaches and targets for treatment of chronic obstructive pulmonary disease.
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PMID:Novel approaches and targets for treatment of chronic obstructive pulmonary disease. 1055 74


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