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  • Title: Clarithromycin prevents smoke-induced emphysema in mice.
    Author: Nakanishi Y, Kobayashi D, Asano Y, Sakurai T, Kashimura M, Okuyama S, Yoneda Y, Shapiro SD, Takayama K.
    Journal: Am J Respir Crit Care Med; 2009 Feb 15; 179(4):271-8. PubMed ID: 19060231.
    Abstract:
    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 vitro test, CAM at 5 to 20 microM 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.
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