Mizoribine protects against bleomycin-induced lung injury.
Bleomycin (BLM)-induced lung injury has become a model for studies of interstitial pneumonitis and pulmonary fibrosis. BLM induces lung injury in two phases: early inflammation characterized by infiltration of inflammatory cells into the lungs, followed by a late phase of fibrosis characterized by deposition of collagen. In this study, we examined the role of mizoribine (MZB) in the regulation of inflammatory tissue injury caused by BLM. We examined the role of MZB using a mouse model of BLM-induced lung injury. We demonstrated that mice subjected to instillation of BLM into the lungs had a significantly increased number of macrophages and lymphocytes in bronchoalveolar lavage fluid (BALF), but that those treated with MZB in the early phase showed a significant reduction in the total number of BALF macrophages and lymphocytes. However, MZB was unable to inhibit fibrosis in the late phase of BLM injury. Our findings suggest that MZB inhibits the proliferation of both lymphocytes and macrophages in the early phase of the BLM-induced acute inflammatory response, as well as its development and amplification, but does not inhibit fibrotic change in the late phase.
Matsui
Kiyoshi
K
Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. k-matsui@hyo-med.ac.jp
Ueda
Haruyasu
H
Terada
Makoto
M
Azuma
Naoto
N
Okamura
Haruki
H
Sano
Hajime
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012263:Ribonucleosides / Q000494:pharmacology*; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D001761:Bleomycin; C010052:mizoribine; D006909:Hydroxyproline