Simvastatin suppresses airway IL-17 and upregulates IL-10 in patients with stable COPD

Abstract

© 2015 American College of Chest Physicians. BACKGROUND: Statins have immunomodulatory properties that may provide benefi cial eff ects 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: Th irty patients with stable COPD were recruited to a double-blind, randomized, controlled, crossover trial comparing the eff ect of simvastatin, 20 mg po daily, with that of a matched placebo on sputum infl ammatory markers and airway infl ammation. Each treatment was administered for 4 weeks separated by a 4-week washout period. Th e primary outcome was the presence of T-helper 17 cytokines and indoleamine 2,3-dioxygenase (IDO) in induced sputum. Secondary outcomes included sputum infl ammatory cells, FEV 1, 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, 2 16.4 pg/mL, P 5.01; 2 48.6 pg/mL, P <.001; 2 45.3 pg/mL, P 5.002; and 2 190.9 pg/mL, P 5.007, 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 diff erence, 24.7 pg/mL, P <.001; 1.02, P <.001; and 0.47, P <.001, respectively). Th e absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced aft er simvastatin compared with placebo (mean diff erence, 2 0.16 × 10 6, P ≤.004; 2 14.1%, P <.001; and 2 3.2, P 5.02, 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.