期刊
CHEST
卷 148, 期 5, 页码 1164-1176出版社
ELSEVIER SCIENCE BV
DOI: 10.1378/chest.14-3138
关键词
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资金
- Siriraj Grant for Research Development and Medical Education [R015633011]
- Faculty of Medicine Siriraj Hospital, Mahidol University
- Medical Research Council [GI001367/1]
- Wellcome Trust [093080/Z/10/Z]
- National Institute for Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton National Health Service Foundation Trust and Imperial College London
- National Institute for Health Research [NF-SI-0611-10148] Funding Source: researchfish
BACKGROUND: Statins have immunomodulatory properties that may provide beneficial effects in the treatment of COPD. We investigated whether a statin improves the IL-17/IL-10 imbalance in patients with COPD, as has previously been demonstrated in patients with asthma. METHODS: Thirty patients with stable COPD were recruited to a double-blind, randomized, controlled, crossover trial comparing the effect of simvastatin, 20 mg po daily, with that of a matched placebo on sputum inflammatory markers and airway inflammation. Each treatment was administered for 4 weeks separated by a 4-week washout period. The primary outcome was the presence of T-helper 17 cytokines and indoleamine 2,3-dioxygenase (IDO) in induced sputum. Secondary outcomes included sputum inflammatory cells, FEV1, and symptoms using the COPD Assessment Test (CAT). RESULTS: At 4 weeks, there was a significant reduction in sputum IL-17A, IL-22, IL-6, and CXCL8 concentrations (mean difference, -16.4 pg/mL, P = .01; -48.6 pg/mL, P < .001; -45.3 pg/mL, P = .002; and -190.9 pg/mL, P = .007, respectively), whereas IL-10 concentrations, IDO messenger RNA expression (fold change), and IDO activity (kynurenine to tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference, 24.7 pg/mL, P < .001; 1.02, P < .001; and 0.47, P < .001, respectively). The absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced aft er simvastatin compared with placebo (mean difference, -0.16 3 10 6, P = .004; -14.1%, P < .001; and -3.2, P = .02, respectively). Values for other clinical outcomes were similar between the simvastatin and placebo treatments. CONCLUSIONS: Simvastatin reversed the IL-17A/IL-10 imbalance in the airways and reduced sputum macrophage but not neutrophil counts in patients with COPD.
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