Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy

Benjamin B Davis, Amir A. Zeki, Jennifer M. Bratt, Lei Wang, Simone Filosto, William F. Walby, Nicholas J. Kenyon, Tzipora Goldkorn, Edward S. Schelegle, Kent E. Pinkerton


COPD is the third leading cause of death. The statin drugs may have therapeutic potential in respiratory diseases such as COPD, but whether they prevent bronchial epithelial injury is unknown. We hypothesized that simvastatin attenuates acute tobacco smoke-induced neutrophilic lung inflammation and airway epithelial injury. Spontaneously hypertensive rats were given simvastatin (20 mg·kg−1 i.p.) daily for either seven days prior to tobacco smoke exposure and during 3 days of smoke exposure, or only during tobacco smoke exposure.

Pre-treatment with simvastatin prior to and continued throughout smoke exposure reduced the influx of total leukocytes, neutrophils, and macrophages into the lung and airways. Simvastatin attenuated tobacco smoke-induced cellular infiltration into lung parenchymal and airway subepithelial and interstitial spaces. One week of simvastatin pre-treatment almost completely prevented smoke-induced denudation of the airway epithelial layer, while simvastatin given only concurrently with the smoke exposure had no effect.

Simvastatin may be a novel adjunctive therapy for smoke-induced lung diseases such as COPD. Given the need for statin pre-treatment there may be a critical process of conditioning that is necessary for statins’ anti-inflammatory effects. Future work is needed to elucidate the mechanisms of this statin protective effect.