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)

The neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.
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PMID:Interleukin-8 induces neutrophil accumulation but not protease secretion in the canine trachea. 147 6

To study the role of T cells in diffuse panbronchiolitis (DPB), we investigated T-cell subsets in bronchoalveolar lavage fluid (BALF) or 33 patients with DPB, nine patients with bronchiectasis, and 20 healthy volunteers. BALF from DPB patients contained a higher percentage of neutrophils than that from patients with bronchiectasis or healthy volunteers, whereas the percentage of lymphocytes was similar in the three groups. DPB patients, however, had a higher number of lymphocytes and a reduced CD4/CD8 ratio compared with the other subjects. A two-color analysis of T-cell subsets in peripheral blood and BALF revealed a significant increase in the percentage and number of CD8+HLA-DR+ cells and in the number of CD4+HLA-DR+ cells in BALF of DPB patients. The expression of the adhesion molecules CD 11a and CD18 on lung CD3+ cells was enhanced over that on blood CD3+ cells in DPB patients. However, there was no significant difference in the expression of these antigens in peripheral blood or BALF among the groups. There was no significant relationship between BALF interleukin (IL)-8 and lymphocyte accumulation in the lungs of the DPB patients, whereas a significant correlation between the percentage of neutrophils and IL-8 levels in BALF of DPB patients was observed. After treatment with macrolide antibiotics, a significant reduction in the number of lymphocytes and activated CD8+ cells and an elevation in the CD4/CD8 ratio in BALF of DPB patients was observed. Our findings suggest an activation of CD8+ cells in the airway lumen of DPB patients, supporting the hypothesis that lymphocytes are important cellular components of bronchial inflammation in DPB.
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PMID:Increase in activated CD8+ cells in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis. 763 15

The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has traditionally been seen as a physiological response to continuous opportunistic infection. Recent studies suggest, however, that regulation of the inflammatory response itself may be altered in CF. Neutrophil migration from the bloodstream involves alterations in surface expression of the adhesion molecules L-selectin and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16) and acutely infected (n = 13) CF patients and 15 normal control subjects were directly assessed by Fluorescence-activated cell sorter (FACS) analysis for surface expression of L-selectin and CD11b before and after stimulation with interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and acutely infected (n = 5) non-CF bronchiectasis patients were also assessed. Surface upregulation of CD11b was similar in all groups. Basal levels of L-selectin were also comparable among all groups, however, when stimulated, neutrophils from both stable and acutely infected CF patients shed significantly less L-selectin than those from control subjects (p < 0.05 and p < 0.01, respectively). This decreased responsiveness was not observed in either stable or acutely infected non-CF bronchiectasis patients. These results add to the accumulating evidence suggestive of a defective inflammatory response in CF.
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PMID:Neutrophil adhesion molecule surface expression and responsiveness in cystic fibrosis. 951 87

Although corticosteroid therapy might be clinically beneficial for bronchiectasis, very little is known of its effects on the inflammatory and infective markers in bronchiectasis. We have therefore performed a double-blind, placebo-controlled study to evaluate the effects of a 4-wk administration of inhaled fluticasone in bronchiectasis. Twenty-four patients (12 female; mean age 51 yr) were randomized into receiving either inhaled fluticasone (500 microgram twice daily) via the Accuhaler device (n = 12) or placebo. At each visit, spirometry, 24-h sputum volume, sputum leukocyte density, bacterial densities, and concentrations of interleukin (IL)-1beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), and leukotriene B4 (LTB4) were determined. There was a significant (p < 0.05) decrease in sputum leukocyte density and IL-1beta, IL-8, and LTB4 after fluticasone treatment. The fluticasone group had one and the placebo group three episodes of exacerbation. There were no significant changes in spirometry (p > 0.05) or any reported adverse reactions in either group. The results of this study show that high-dose fluticasone is effective in reducing the sputum inflammatory indices in bronchiectasis. Large-scale and long-term studies are indicated to evaluate the effects of inhaled steroid therapy on the inflammatory components in bronchiectasis.
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PMID:Inhaled fluticasone reduces sputum inflammatory indices in severe bronchiectasis. 973 Sep 96

Patients with bronchiectasis suffer from sputum production, recurrent exacerbations, and progressive airway destruction. Erythromycin is effective in diffuse panbronchiolitis, another suppurative airway disorder, although its efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin (500 mg b.i.d.) in steady-state idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female, mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/-16 yrs) had significantly improved forced expiratory volume in one second, forced vital capacity and 24-h sputum volume after 8 weeks (p<0.05). There was no parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis. Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis.
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PMID:A pilot study of low-dose erythromycin in bronchiectasis. 1006 82

The acquisition of Pseudomonas aeruginosa in the airways of patients with cystic fibrosis (CF) is the initial event leading to bronchiectasis and lung disease. Although the host factors that permit initial airway colonization are largely unknown, recent studies suggest that secretion of interleukin (IL)-8 by airway epithelia and local recruitment of neutrophils is the final pathway in a pulmonary cytokine network. To determine whether differences in cytokine production exist between normal and CF airway epithelia, secretion of immunoreactive IL-8 and IL-10 as well as specific messenger RNA (mRNA) abundance were compared in airway epithelia expressing normal and mutant CF transmembrane regulator. After induction with IL-1beta, a CF airway cell line engineered to express the wild-type CF gene (CFT1-LCFSN) secreted significantly more immunoreactive IL-8 than did its isogenic parent that expressed the mutant CF gene (CFT1) or an isogenic vector control line (CFT1-LC3). Further studies with the three related cell lines demonstrated that expression of CFT1-LCFSN was associated with a significant increase in uninduced secretion of immunoreactive IL-8 as well as a 10- to 20-fold increase in IL-8 mRNA abundance when compared with the isogenic lines expressing the mutant gene. IL-1beta induction and intracellular accumulation of IL-8 appeared to be unaffected by CF genotype. These studies suggest that IL-8 secretion by CF airway epithelial cells is defective and may contribute to Pseudomonas persistence in the CF airway. Further studies are needed to confirm this difference in other cell lines and determine the linkage between IL-8 production and CF gene expression.
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PMID:Reduced interleukin-8 production by cystic fibrosis airway epithelial cells. 1022 79

The dominant role of inflammation in airways disease progression in cystic fibrosis (CF) is now well established and, based on recent findings, the possibility of an inappropriate inflammatory response in the lung of patients with CF has emerged. In order to characterize this response, the aim of the present work was to evaluate the levels of a number of pro- and anti-inflammatory cytokines in the sputum of CF children and to compare these levels to those observed in the sputum from non-CF children with diffuse bronchiectasis (DB). Three groups of patients were investigated: a group of 25 CF children (mean age: 12.2 yrs), a group of 10 non-CF children with DB (mean age 11.5 yrs), and a group of five healthy young adults (mean age 24 yrs). Elevated concentrations of pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were found in children with CF and in non-CF children with DB, with significantly higher concentrations of IL-1beta in CF children. Analysis of the natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) and type II TNF soluble receptor (sTNFRII) concentrations showed distinct patterns, with elevated levels of both inhibitors in CF patients, whereas only sTNFRII was found to be increased in non-CF children with DB. IL-10 data indicated low concentrations in the CF group. In all CF children, the concentrations of IL-6 in the airways were extremely low, independent of the clinical, bacteriological or functional status. By contrast, significantly increased IL-6 levels were found in non-CF children with DB. These results document distinct cytokine profiles in cystic fibrosis patients and noncystic fibrosis patients. They also suggest that impairment of interleukin-6 expression may represent an important component of the excessive inflammatory response observed in cystic fibrosis.
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PMID:Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease. 1051 11

Cystic fibrosis (CF) is a lethal, hereditary disorder characterized by a neutrophil-dominated inflammation of the lung. We sought to determine whether neutrophils from individuals with CF release more neutrophil elastase (NE) than neutrophils from normal subjects. Our results showed that peripheral blood neutrophils (PBNs) from normal subjects and individuals with CF contained similar amounts of NE, but after preincubation with CF bronchoalveolar lavage (BAL) fluid, significantly more NE was released by CF PBNs, a release that was amplified further by incubation with opsonized Escherichia coli. To determine which components of CF BAL fluid stimulated this excessive NE release from CF PBNs, we repeated the experiments after neutralization or immunoprecipitation of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 in CF BAL fluid. We found that subsequent NE release from CF PBNs was reduced significantly when TNF-alpha and IL-8 were removed from CF BAL fluid. When TNF-alpha and IL-8 were used as activating stimuli, CF PBNs released significantly greater amounts of NE compared with PBNs from control subjects and individuals with bronchiectasis. These results indicate that CF PBNs respond abnormally to TNF-alpha and IL-8 in CF BAL fluid and react to opsonized bacteria by releasing more NE. This may help explain the increased NE burden seen in this condition.
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PMID:Increased elastase release by CF neutrophils is mediated by tumor necrosis factor-alpha and interleukin-8. 1064 88

Endothelin (ET)-1 has been suggested to promote neutrophil adhesion to endothelium, migration to inflamed areas, and release of elastase. ET-1 might therefore play a role in the pathogenesis of bronchiectasis, a chronic inflammatory and infective airway disease which is still poorly understood. Thirty five patients with stable bronchiectasis (20 females, mean age+/-SD 49.1+/-15.0 yrs) and 18 control subjects (8 females, 49.4+/-11.3 yrs) were recruited prospectively. The ET-1 levels in serum and sputum were measured by commercially available enzyme linked immunosorbent assay (ELISA) kits. Patients with Pseudomonas aeruginosa in their sputum had a significantly higher serum level of ET-1 (median 25.8, interquartile range 13-43.9 pg x mL(-1)) than patients without P. aeruginosa (0, 0-10.5 pg x mL(-1); p=0.0004) and healthy control subjects (4.6, 0-16.3 pg x mL(-1); p=0.002). However, patients with and without P. aeruginosa infection had no significant difference in sputum ET-1 level (p=0.15). There was no correlation between serum or sputum ET-1 levels with the serum and sputum levels of the interleukin (IL)-1beta, IL-8 and tumour necrosis factor (TNF)-alpha; the number of bronchiectasis lung lobes; and spirometry. Serum ET-1 level correlated with 24 h sputum volume for the bronchiectasis patients (r=0.51, p=0.002). The results, therefore, suggest a significant pathogenic role for endothelin-1 among Pseudomonas aeruginosa-infected patients with bronchiectasis. Further studies should be performed to evaluate the clinico-pathological correlation and expression of endothelin-1 in bronchiectasis.
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PMID:Endothelin-1 in stable bronchiectasis. 1093 1

To evaluate the bronchial inflammatory response and its relationship to bacterial colonization in bronchiectasis, we performed a bronchoalveolar lavage (BAL) in 49 patients in stable clinical condition and in nine control subjects. BAL was processed for differential cell count, quantitative bacteriologic cultures, and measurement of inflammatory mediators. An increase was observed in the percentage of neutrophils (37 [0 to 98]) (median[range]) versus 1[0 to 4]%, p = 0.01), in the concentration of elastase (90.5 [8 to 2,930] versus 34 [9 to 44], p = 0.03), myeloperoxidase (9.1 [0 to 376] versus 0.3 [0.1 to 1.4], p = 0.01), and in the levels of TNF-alpha (4 [0 to 186] versus 0 [0 to 7], p = 0.03), IL-8 (195 [0 to 5,520] versus 3 [0 to 31], p = 0.001), and IL-6 (6 [0 to 115] versus 0 [0 to 3], p = 0.001) in patients with bronchiectasis compared with control subjects. Noncolonized patients showed a more intense bronchial inflammatory reaction than did control subjects. This inflammatory reaction was exaggerated in patients colonized by microorganisms with potential pathogenicity (MPP), with a clear relationship with the bronchial bacterial load. Patients with bronchiectasis showed a slight systemic inflammatory response, with poor correlations between systemic and bronchial inflammatory mediators, suggesting that the inflammatory process was mostly compartmentalized. We conclude that patients with bronchiectasis in a stable clinical condition present an active neutrophilic inflammation in the airways that is exaggerated by the presence of MPP, and the higher the bacterial load the more intense the inflammation.
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PMID:Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. 1171 1


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