Clarithromycin Prevents Smoke-induced Emphysema in Mice

Rationale Modulating the low-grade chronic Inflammation In chronic obstructive pulmonary disease remains challenging. Clarithromycin (CAM), a macrolide antibiotic, reportedly ameliorates chronic Inflammation via mechanisms Independent of its antibacterial activity. Objectives: The aim of this study was to examine whether CAM can prevent or reduce emphysema Induced by chronic cigarette smoke exposure. Methods: Mice were exposed to cigarette smoke daily for 6 months and treated with orally administered CAM at doses of 25 to 100 mg/kg twice a day throughout the course of the experiment to test the preventive effects. The administration of CAM at 50 or 100 mg/kg was performed during the second half of a 6-month exposure period to assess the therapeutic effects. Histologic analysis was performed to evaluate the effect of CAM. Measurements and Main Results: CAM treatment for 6 months decreased airspace enlargement and the destruction of the alveolar walls and impaired the accumulation of macrophages In bronchoalveolar lavage fluid In a dose-related fashion. The administration of clarithromycin at 100 mg/kg in the therapeutic protocol reduced emphysema compared with the smoke-exposed group without treatment. An immunohistologic analysis revealed that CAM reduced the number of F4/80-positive macrophages in the lung parenchyma. In an in vitrotest, CAM at 5 to 20 mu M directly suppressed the activation of macrophages stimulated with tumor necrosis factor-alpha, Conclusions: Our data demonstrated that CAM at a clinically achievable dose prevented cigarette smoke-induced emphysema by modulating lung inflammation. This study supports the possibility that low-dose CAM treatment might provide a new therapeutic strategy for chronic obstructive pulmonary diseases,