Clarithromycin prevents smoke-induced emphysema in mice.
BACKGROUND
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.


OBJECTIVE
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.


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.
Nakanishi
Yutaka
Y
Research Center, Taisho Pharmaceutical Co., Ltd., 403, Yoshino-Cho 1-Chome, Kita-Ku, Saitama City, Saitama, Japan.
Kobayashi
Dale
D
Asano
Yasuo
Y
Sakurai
Takanobu
T
Kashimura
Masato
M
Okuyama
Shigeru
S
Yoneda
Yukio
Y
Shapiro
Steven D
SD
Takayama
Kiyoshi
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001992:Bronchoalveolar Lavage Fluid; D017291:Clarithromycin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004646:Emphysema / Q000209:etiology / Q000517:prevention & control*; D004781:Environmental Exposure; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction / Q000379:methods; D014028:Tobacco Smoke Pollution; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D014028:Tobacco Smoke Pollution; D017291:Clarithromycin