Tacrolimus (FK506) has protective actions against murine bleomycin-induced acute lung injuries.
The effects of tacrolimus on murine acute lung injury were tested, especially in comparison to dexamethasone. Acute lung injury was induced by intratracheal instillation of bleomycin. Oral tacrolimus significantly improved survival rates of bleomycin-exposed mice, while cyclosporin A or dexamethasone did not. After instillation of bleomycin (day 0), a migration of neutrophils into alveolar spaces peaked on day 3, with concomitant increases of chemokines. On day 6, marked morphological changes in the lungs were observed. All these changes were significantly inhibited by tacrolimus. Furthermore, DNA ladder and immunohistochemical analyses of lungs showed that apoptosis of lung cells appeared on day 6 and was abolished only by the treatment of tacrolimus. These results suggest that both anti-inflammatory and anti-apoptotic action of tacrolimus contribute to improvement of bleomycin-induced acute lung injury.
Koshika
Tadatsura
T
Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. tadatsura_koshika@po.fujisawa.co.jp
Hirayama
Yoshitaka
Y
Ohkubo
Yoshitaka
Y
Mutoh
Seitaro
S
Ishizaka
Akitoshi
A
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use
D018925:Chemokines; D007166:Immunosuppressive Agents; D001761:Bleomycin; D003907:Dexamethasone; D016559:Tacrolimus