Statins Reduce Ambient Particulate Matter-Induced Lung Inflammation by Promoting the Clearance of Particulate Matter <10 μm From Lung Tissues

Background: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter <10 mu m (PM10)-induced inflammatory response in vitro. The aim of this study was to determine the effect of statins on PM10-induced lung inflammation in vivo. Methods: New Zealand white rabbits were exposed to either PM10 (1.0 mg/kg) or saline by direct intratracheal instillation three times a week for 4 weeks +/- lovastatin 5.0 mg/kg/d. BAL fluid was assessed for cell counts and proinflammatory cytokine levels. Lung inflammation was quantified using immunohistochemical techniques and morphometric methods. Ex vivo phagocytosis assay of alveolar macrophages using PM particles was performed. Distribution of PM10 particles in lung tissues and draining lymph nodes was quantified morphometrically to evaluate the clearance of PM10 particles. Results: PM10 exposure increased the production of IL-6 and IL-8, promoted the recruitment of macrophages and polymorphonuclear leukocytes into the lung, and activated these recruited leukocytes. Lovastatin significantly suppressed all these effects. Lovastatin increased the phagocytic activity of macrophages and promoted the migration of PM10-laden macrophages to the regional lymph nodes. Conclusions: Lovastatin attenuates the PM10-induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinflammatory cytokine production, and promotes the clearance of PM10 particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM10-induced lung inflammation. CHEST 2013; 143(2):452-460