Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Leukotrienes play an important role in IPF, and leukotriene (LT)B4 is one of the key eicosanoids in IPF. In this study, we investigated whether ONO-4057, a LTB4 receptor (BLTR) antagonist is capable of preventing bleomycin-induced pulmonary fibrosis. On day 1, C57BL/6 male mice were given a single intratracheal injection of bleomycin (2.5 mg·kg-1), and ONO-4057 (1.0 mg·kg-1) or vehicle alone, administered by intraperitoneal injection on days 1-5 each week for 3 weeks after the bleomycin injection. ONO-4057 reduced the total cell count in bronchoalveolar lavage fluid (BALF) on days 7, 14 and 21 and the Ashcroft score and the lung hydroxyproline content on days 14 and 21. The LTB 4, interleukin (IL)-6, IL-13, transforming growth factor (TGF)-β levels in BALF and the TGF-β expression in lung tissue, assessed by immunohistochemistry were decreased on day 7, whereas interferon (IFN)-γ level in BALF was increased on day 14. The results of this study indicated that the BLTR antagonist inhibited the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation and altering TGF-β, IL-6, IL-13 and IFN-γ. Copyright©ERS Journals Ltd 2009.