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)

Neutrophils are reported to be a major factor in the pathogenesis of the adult respiratory distress syndrome (ARDS). We measured serial levels of circulatory interleukin (IL)-8 and neutrophil elastase in 16 patients with ARDS at the onset, on day 3 and on day 7 and studied the relationship of these levels to the clinical course. Circulatory IL-8 levels of all the patients at the onset were significantly elevated compared with controls, mean +/- SE, 30.0 +/- 6.7 pg/ml and 3.3 +/- 0.3 pg/ ml, respectively. There was a significant correlation between IL-8 and neutrophil elastase levels at the onset (r = 0.65, p < 0.01). In nonsurvivors circulatory IL-8 levels were significantly higher than those of survivors throughout the study. There were significant differences in oxygenation, as reflected by PaO2/FIO2 ratios, between survivors and nonsurvivors at day 7, mean +/- SE, 208.5 +/- 21.9 and 113.5 +/- 9.6, respectively. In conclusion, we have shown that the level of circulatory IL-8 is elevated in patients with ARDS, and sustained high levels of circulatory IL-8 might be correlated with a poor outcome.
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PMID:Sustained high levels of circulatory interleukin-8 are associated with a poor outcome in patients with adult respiratory distress syndrome. 896 89

Neutrophils play an important role in inflammatory processes in the lung and may cause tissue injury through, for example, release of proteinases such as neutrophil elastase. In addition to neutrophil elastase, stimulated neutrophils also release small nonenzymatic and cationic polypeptides termed defensins. The aim of the present study was to investigate whether defensins induce interleukin (IL)-8 expression in cells of the A549 lung epithelial cell line and in human primary bronchial epithelial cells (PBEC). Supernatants of defensin-treated A549 cells contained increased neutrophil chemotactic activity (16-fold) that was inhibited by antibodies against IL-8. Concurrently, within 3 and 6 h, defensins significantly increased the IL-8 levels in supernatants of both A549 cells (n = 6, P < 0.05 and P < 0.01, respectively) and PBEC (n = 4, P < 0.001 and P < 0.001, respectively). This defensin-induced increase was fully inhibited by the serine proteinase inhibitor alpha 1-proteinase inhibitor. In addition, defensins also increased IL-8 mRNA levels (12-fold); this increase was dependent on de novo mRNA synthesis and did not require protein synthesis. Furthermore, defensins did not affect IL-8 mRNA stability, indicating that the enhanced IL-8 expression was due to increased transcription. Our findings suggest that defensins, released by stimulated neutrophils, stimulate IL-8 synthesis by airway epithelial cells and thus may mediate the recruitment of additional neutrophils into the airways.
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PMID:Effect of defensins on interleukin-8 synthesis in airway epithelial cells. 917 53

The objective of our study was to elucidate the involvement of interleukin (IL)-8 in the hCG-induced rabbit ovulatory process. After administering hCG (100 IU i.v.), we examined myeloperoxidase (MPO) activity, which represents neutrophil accumulation; neutrophil elastase (NE) activity, which is an indicator of neutrophil activity; and levels of IL-8 in the ovaries. The maximal level of IL-8 was observed before MPO and NE activities reached a peak: production of IL-8, MPO, and NE activities peaked, respectively, at 4 h (5.58 +/- 0.88 pg/mg ovary, n = 13), 6 h (1.07 +/- 0.13 deltaA/min per gram ovary, n = 8), and 9 h (18.89 +/- 1.05 U/g ovary, n = 8). Anti-rabbit IL-8 antiserum given i.v. significantly reduced the maximal levels of hCG-induced MPO activity (antiserum vs. control; 0.34 +/- 0.04 vs. 1.12 +/- 0.11 deltaA/min per gram ovary, n = 14, p < 0.001) and NE activity (8.14 +/- 0.85 vs. 18.30 +/- 0.79 U/g ovary, n = 14, p < 0.001). The hCG-induced ovulation rate was significantly inhibited by the antiserum (50.5% vs. 83.9%, n = 14, p < 0.001). Intraperitoneal injection of 100 mg/kg of ONO-5046, a specific NE inhibitor, also attenuated the ovulation rate (ONO-5046 vs. vehicle; 56.0% vs. 74.0%, n = 14, p < 0.05). These findings clearly indicate that IL-8 has an important role in the hCG-induced ovulatory process through the accumulation and activation of neutrophils.
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PMID:Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process: interleukin-8 induces neutrophil accumulation and activation in ovulation. 947 10

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

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


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