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 oral simvastatin 20 mg 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 Th17 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=0.01; –48.6 pg/ml, p<0.001; –45.3 pg/ml, p=0.002 and –190.9 pg/ml, p=0.007, respectively), whereas IL-10 concentrations, IDO mRNA expression (fold change) and IDO activity (kynurenine/tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference 24.7 pg/ml, p<0.001; 1.02, p<0.001 and 0.47, p<0.001, respectively). The absolute sputum macrophage count, proportion of macrophages and CAT score was reduced after simvastatin compared with placebo (mean difference –0.16 ×106, p=0.004; –14.1%, p<0.001 and –3.2, p=0.02, respectively). Values for other clinical outcomes were similar between the simvastatin and placebo treatments.
Conclusion: Simvastatin reversed the IL-17A/IL-10 imbalance in the airways and reduced sputum macrophage but not neutrophil counts in patients with COPD.