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      Expression levels of induced sputum IL-8 and IL-10 and drug intervention effects in patients with acute exacerbated COPD complicated with chronic cor pulmonale at high altitude

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          Abstract

          The aim of this study was to assess the expression levels of induced sputum interleukin (IL)-8 and IL-10 levels in patients with acute exacerbated chronic obstructive pulmonary disease (AECOPD) complicated with chronic cor pulmonale (CCP) at high altitude, and to evaluate the intervention effects of an inhaled corticosteroid (ICS) and a β 2-adrenoceptor agonist in this disease. A total of 186 patients with AECOPD complicated with CCP were randomly divided into three groups, with 62 cases in each. With regard to the two treatment groups, group A was treated with salmeterol/fluticasone (50 μg/250 μg, respectively) by airway inhalation twice daily, while group B received budesonide (1 mg) as a spray inhalation, twice daily. The routine treatment group (group C) received only routine treatment. The levels of IL-8 and IL-10 in the induced sputum and the predicted percentage of forced expiratory volume in one second (FEV 1%pred), partial pressure of oxygen in arterial blood (PaO 2) and partial pressure of carbon dioxide in arterial blood (PaCO 2) were examined on admission and at a stable stage two weeks following treatment. Forty healthy volunteers served as a control group (group D). Compared with group D values, the IL-8 induced sputum level and the PaCO 2 were significantly increased, while the level of IL-10, FEV 1%pred and the PaO 2 were markedly decreased in the three COPD groups prior to treatment. Following treatment, the induced sputum IL-8 level and the PaCO 2 were significantly decreased, while the induced sputum IL-10 level, FEV 1%pred and the PaO 2 were markedly increased in the three treatment groups compared with the values pre-therapy (all P<0.01). The post-treatment parameters were significantly different among the three groups (P<0.01). The results indicate that IL-8 and IL-10 are involved in the airway inflammation of AECOPD complicated by CCP. Treatment with an ICS was demonstrated to be a successful method of reducing the local expression of IL-8 and increasing the local expression of IL-10; however, ICS combined with a long-acting β 2-adrenoceptor agonist (LABA) was more effective than the sole administration of ICS in patients with AECOPD complicated by CCP at high altitude.

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          Interleukin-10 therapy--review of a new approach.

          Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Its main biological function seems to be the limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells such as T cells, B cells, natural killer cells, antigen-presenting cells, mast cells, and granulocytes. However, very recent data suggest IL-10 also mediates immunostimulatory properties that help to eliminate infectious and noninfectious particles with limited inflammation. Numerous investigations, including expression analyses in patients, in vitro and animal experiments suggest a major impact of IL-10 in inflammatory, malignant, and autoimmune diseases. So IL-10 overexpression was found in certain tumors as melanoma and several lymphomas and is considered to promote further tumor development. Systemic IL-10 release is a powerful tool of the central nervous system to prevent hyperinflammatory processes by activation of the neuro-endocrine axis following acute stress reactions. In contrast, a relative IL-10 deficiency has been observed and is regarded to be of pathophysiological relevance in certain inflammatory disorders characterized by a type 1 cytokine pattern such as psoriasis. Recombinant human IL-10 has been produced and is currently being tested in clinical trials. This includes rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and chronic hepatitis C. The results are heterogeneous. They give new insight into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a new therapeutic target.
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            Inflammatory cells in the airways in COPD.

            Airway inflammation is central to the pathogenesis of both airway remodelling and parenchymal destruction in chronic obstructive pulmonary disease (COPD). Neutrophils, macrophages, and CD8+ T lymphocytes have been implicated in a number of studies, but a detailed profile of disease-phenotype specific inflammation has yet to emerge. The heterogeneity of the disease has hindered data interpretation while extrapolation of the results of relatively non-invasive studies to the actual pathology found in the distal lung is difficult. Moreover, prominent studies have had frequently conflicting results. Further investigations are needed to marry the different clinical phenotypes of COPD to their respective inflammatory profiles in the airways and thus improve our understanding of the pathogenesis of the disease as a whole.
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              Antiinflammatory effects of salmeterol/fluticasone propionate in chronic obstructive lung disease.

              No currently available treatment is reported to reduce the exaggerated airway wall inflammation of chronic obstructive pulmonary disease. We tested the hypothesis that inhaled combined long-acting beta2-agonist (salmeterol) and corticosteroid (fluticasone propionate) will reduce inflammation. Bronchial biopsies and induced sputum were taken from 140 current and former smokers (mean age, 64 yr) with moderate to severe disease, randomized in a 13-wk double-blind study to placebo (n = 73) or salmeterol/fluticasone propionate 50/500 microg (n = 67) twice daily. Biopsies were repeated at 12 wk and sputa at 8 and 13 wk. After adjustment for multiplicity, comparisons between active and placebo were made for median change from baseline in the numbers of biopsy CD8+ and CD68+ cells/mm2 and sputum neutrophils. Combination therapy was associated with a reduction in biopsy CD8+ cells of -118 cells/mm2 (95% confidence interval [CI], -209 to -42; p = 0.02), a reduction of 36% over placebo (p = 0.001). CD68+ cells were unaffected by combination treatment. Sputum differential (but not total) neutrophils reduced progressively and, at Week 13, significantly with combination treatment (median treatment difference, 8.5%; 95% CI, 1.75%-15.25%; p = 0.04). The combination also significantly reduced biopsy CD45+ and CD4+ cells and cells expressing genes for tumor necrosis factor-alpha and IFN-gamma and sputum total eosinophils (all p < or = 0.03). These antiinflammatory effects were accompanied by a 173-ml (95% CI, 104-242; p < 0.001) improvement in prebronchodilator FEV1. The combination of salmeterol and fluticasone propionate has a broad spectrum of antiinflammatory effects in both current and former smokers with chronic obstructive pulmonary disease, which may contribute to clinical efficacy.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                September 2013
                01 July 2013
                01 July 2013
                : 6
                : 3
                : 747-752
                Affiliations
                [1 ]Center of Respiratory Medicine, The Fourth Hospital of PLA, Lanzhou Command, Xining, Qinghai 810007, P.R. China
                [2 ]Department of Cardiovascular Surgery, Heart Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
                Author notes
                Correspondence to: Dr Shengyue Yang, Center of Respiratory Medicine, The Fourth Hospital of PLA, Lanzhou Command, No. 67 Bayi Dong Road, Xining, Qinghai 810007, P.R. China, E-mail: shengyueyangcn@ 123456163.com
                [*]

                Contributed equally

                Article
                etm-06-03-0747
                10.3892/etm.2013.1192
                3786877
                24137259
                2dae51f6-e604-4d0e-9b82-ee3cf089decc
                Copyright © 2013, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 26 March 2013
                : 19 June 2013
                Categories
                Articles

                Medicine
                interleukin-8,interleukin-10,corticosteroid,β2-adrenoceptor agonist,chronic obstructive pulmonary disease,chronic cor pulmonale

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