Anti-inflammatory effect of pirfenidone in the bleomycin-hamster model of lung inflammation

We have previously reported the antifibrotic effects of pirfenidone (PD) in the bleomycin (BL)-hamster model of lung fibrosis. Since the development o f fibrosis is generally preceded by acute lung inflammation, the present st udy was conducted to find out if dietary intake of PD (0.5%) has any effect s on BL-induced lung inflammation. In this regard, we evaluated the effects of PD on BL-induced increased pulmonary vascular permeability, increased i nflux of inflammatory cells and increased levels of TGF-beta in the broncho alveolar lavage fluid (BALF). Hamsters were intratracheally (IT) instilled with saline (SA) or BL (5.5 units/kg/5 mi). The animals were fed the contro l diet (CD) or the same diet containing 0.5% PD 2 days prior to IT instilla tion and throughout the study. The bronchoalveolar lavage was carried out a t different times after IT instillation. Lavage fluid was used for total an d differential cell counts and BALF-supernatant for measurement of total pr otein and TGF-beta. IT instillation of BL caused significant increases in t otal cells, neutrophils, macrophages and lymphocytes and in the levels of t otal protein and TGF-beta in BALF from hamsters in the BL + CD groups as co mpared to the corresponding SA + CD control groups. In contrast, treatment with pirfenidone in general, suppressed the BL-induced increases in the lev els of proteins and TGF-beta and in the influx of neutrophils, macrophages and lymphocytes in BALF at the early time points in BL + PD groups. Based o n the data reported in this study, we conclude that the anti-inflammatory e ffects of pirfenidone as evident by suppressions of BL-induced increased pu lmonary vascular permeability and increased influx of inflammatory cells in the lung contribute additionally to its inherent anti-fibrotic effect.