title: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT01944176; www.clinicaltrials.gov.
authors.forename: Kittipong
authors.initials: K
authors.lastname: Maneechotesuwan
authors.forename: Adisak
authors.initials: A
authors.lastname: Wongkajornsilp
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000008:administration & dosage*; D013183:Sputum / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508609:IL10 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; D016753:Interleukin-10; D012313:RNA; D019821:Simvastatin