Introduction: Acute respiratory distress syndrome (ARDS) is characterized by an early exudative, inflammatory phase, followed a fibrotic phase. Pirfenidone is a potent anti-fibrotic agent that can inhibit the progression of fibrosis in idiopathic pulmonary fibrosis (IPF)

Aims: The present study investigated the therapeutic efficiency of pirfenidone on ARDS induced by lipopolysaccharide (LPS) and bleomycin in rats.

Methods: ARDS was induced by intra-tracheal instillation of LPS (3 mg/kg) & bleomycin (3 mg/kg) in 0.2 mL normal saline. The pirfenidone treatment groups received an each dose (100 and 200 mg/kg) orally administration of 0.5 mL distilled water including pirfenidone once every 2 days for 20 days, a total 10 times.

Results: Intratracheal administration of LPS and bleomycin caused lung tissue damage and significantly increased the lung injury scores & levels of pro-inflammatory cytokines. Transforming growth factor(TGF)-?1/Smad-2 signaling factors were increased by ARDS induction. Furthermore, it was resulted in matrix metalloproteinases(MMP)-9/tissue inhibitor of metalloproteinase(TIMP)-1 imbalance, which increased fibrotic related factors. Pirfenidone treatment potently suppressed expressions of TGF-?1/Smad-2 signaling factors compared to the non-treated group, in addition, improved MMP-9/TIMP-1 imbalance. These alterations led to the reduction fibrotic factor, pro-inflammatory cytokines which promoted the recovery of damage lung tissue.

Conclusions: Pirfenidone treatment demonstrated therapeutic effects for LPS and bleomycine-induced ARDS compared to the non-treated group. Therefore, pirfenidone may be used as a therapy for initial treatment of ARDS.