EFFECTS OF NEUTROPHIL ELASTASE INHIBITOR ON BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN MICE

Neutrophils play an important role in the pathogenesis of idiopathic p ulmonary fibrosis (IPF). To elucidate the possible involvement of neut rophil elastase (NE) in pulmonary fibrosis, we investigated the effica cy of a new specific NE inhibitor (ONO-5046 . Na) in a murine model of human IPF, bleomycin-induced pulmonary fibrosis. Bronchoalveolar lava ge (BAL) and histopathological analysis were performed on bleomycin-tr eated mice (group A), bleomycin and ONO-5046 . Na-treated mice (group B), and saline control groups at 1, 15, and 29 d after the end of bleo mycin treatment. At 29 d, multifocal fibrosis was observed in group A, whereas no fibrotic regions were observed in group B, Interleukin-1 b eta and macrophage inflammatory protein-2 mRNA levels in BAL cells on day 1, and platelet-derived growth factor-A and insulin-like growth fa ctor-I mRNA levels on days 1 and 15, were significantly lower in group B than in group A. Thus, we demonstrated an inhibitory effect of ONO- 5046 . Na on pulmonary fibrosis in mice, indicating the involvement of NE in the pathogenesis of pulmonary fibrosis. We propose that this ef fect might be related to suppressed expression of particular cytokines in alveolar macrophages and that this specific NE inhibitor could be a novel therapeutic agent for IPF.