Simvastatin Suppresses Airway IL-17 and Upregulates IL-10 in Patients With Stable COPD.

Abstract

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 after simvastatin compared with placebo (mean difference, -0.16 × 106, 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.

TRIAL REGISTRY:

ClinicalTrials.gov; No.: NCT01944176; www.clinicaltrials.gov.

• Authors: Kittipong Maneechotesuwan, Adisak Wongkajornsilp, Ian M Adcock, Peter J Barnes
• Journal: Chest (Chest) Vol. 148 Issue 5 Pg. 1164-76 (Nov 2015) ISSN: 1931-3543 [Electronic] United States
• PMID: 26043025 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• IL10 protein, human
• IL17A protein, human
• Interleukin-17
• Interleukin-10
• RNA
• Simvastatin

Topics

• Aged
• Aged, 80 and over
• Chromatography, Liquid
• Cross-Over Studies
• Double-Blind Method
• Female
• Gene Expression Regulation
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage)
• Interleukin-10 (biosynthesis, genetics)
• Interleukin-17 (biosynthesis, genetics)
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (drug therapy, genetics, metabolism)
• RNA (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Simvastatin (administration & dosage)
• Sputum (metabolism)