Mizoribine protects against bleomycin-induced lung injury

• Published in: Modern rheumatology Vol. 20; no. 5; pp. 471 - 477
• Main Authors: Matsui, Kiyoshi, Ueda, Haruyasu, Terada, Makoto, Azuma, Naoto, Okamura, Haruki, Sano, Hajime
• Format: Journal Article
• Language: English
• Published: United States Informa Healthcare 01-10-2010; Taylor & Francis
• Subjects: Animals; Antibiotics, Antineoplastic - toxicity; Bleomycin - toxicity; Bleomycin-induced lung injury; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Cell Count; Cell Proliferation - drug effects; Disease Models, Animal; Female; Hydroxyproline - metabolism; Immunosuppressive Agents - pharmacology; Inflammatory phase; Interstitial pneumonia; Lung - drug effects; Lung - metabolism; Lung Diseases, Interstitial - chemically induced; Lung Diseases, Interstitial - pathology; Lung Diseases, Interstitial - prevention & control; Lymphocytes - drug effects; Lymphocytes - pathology; Macrophages - drug effects; Macrophages - pathology; Mice; Mice, Inbred C57BL; Mizoribine; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - pathology; Pulmonary Fibrosis - prevention & control; Ribonucleosides - pharmacology; Time Factors
• ISSN: 1439-7595; 1439-7609
• DOI: 10.3109/s10165-010-0312-8

Abstract
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.