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Science Translational Medicine  25 Nov 2015:
Vol. 7, Issue 315, pp. 315ec201
DOI: 10.1126/scitranslmed.aad5916

Statins, which are typically used for lowering cholesterol, have immunomodulatory effects in asthma and reportedly reduce sputum macrophage count and improve the balance of inflammatory cells in favor of suppressing inflammation. Prior studies suggest that chronic obstructive pulmonary disease (COPD) may have an autoimmune component related to T helper 17 (TH17) cells, a subset of CD4+ T cells found in COPD. In addition, statins have proven immunomodulatory effects on TH17cell- and interleukin-17 (IL-17)–mediated inflammatory responses in a number of autoimmune diseases. On the basis of this information, Maneechotesuwan and colleagues conducted a study to determine whether simvastatin has beneficial effects in COPD similar to those seen in asthma.

The study was a double-blind, randomized, cross-over trial. Twenty-six individuals aged 45 to 80 years, with moderate COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II], went through a 2-week run-in period before being randomized to receive 20 mg of simvastatin or placebo for 4 weeks. Participants were subsequently subjected to a 4-week washout period, after which they crossed over to the opposite treatment arm. The authors then measured the concentrations of TH17 cytokines and indoleamine 2,3-dioxygenase in induced sputum from these patients. Additional outcome measures evaluated in the study included sputum inflammatory cells, extent of respiratory dysfunction, and symptoms. The concentrations of cytokines IL-17 and IL-22 were reduced in the sputum of COPD patients treated with simvastatin, independent of smoking status or use of inhaled corticosteroids. In addition, simvastatin suppressed sputum IL-6 concentrations, whereas placebo had the opposite effect. Simvastatin also improved the patients’ symptoms but did not alter the objective measurements of lung function.

This study describes the anti-inflammatory effects of statins in COPD. The results indicate that simvastatin may help modulate the inflammatory response in patients with COPD, but these findings must be interpreted with caution because this was a small study restricted to individuals with moderate disease. Additional work will be required to determine whether the observations noted in this study are generalizable to other COPD groups/classes. Another limitation to consider is that despite the washout period before switching treatment arms, the randomized cross-over design may have affected the results if the carry-over effect was prolonged.

K. Maneechotesuwan et al., Simvastatin suppresses airway IL-17 and upregulates IL-10 in patients with stable COPD. Chest 148, 1164–1176 (2015). [Full Text]

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