Preventive effect of irbesartan on bleomycin-induced lung injury in mice.

BACKGROUND Idiopathic pulmonary fibrosis is a specific form of chronic fibrosing interstitial pneumonia that is limited to the lung. Angiotensin receptor blockers (ARBs) and peroxisome proliferator-activated receptor (PPAR) γ ligands have anti-inflammatory and anti-fibrotic effects. We investigated the effects of irbesartan-an ARB with PPAR γ activity-on the development of bleomycin-induced pulmonary fibrosis in mice. METHODS Lung injury was induced in imprinting control region (ICR) mice by intratracheal instillation of 2mg/kg of bleomycin. The treatment group orally received 20mg/kg of irbesartan for 5 consecutive days before instillation. The mice were sacrificed and were evaluated 14 days after bleomycin instillation. RESULTS Irbesartan reduced the fluid content and hydroxyproline level in the lung and improved the pathological findings as indicated by the Ashcroft score. Total cell counts, the numbers of macrophages, neutrophils, and lymphocytes, and the levels of transforming growth factor (TGF) β1 and monocyte chemotactic protein (MCP) 1 in the bronchoalveolar lavage fluid (BALF) were decreased. Treatment with a PPARγ antagonist GW9662 reversed some of the effects of irbesartan. CONCLUSIONS The results of this study indicated that irbesartan attenuated the development of bleomycin-induced pulmonary fibrosis in mice by decreasing TGF-β1 and MCP-1 via blocking of ATI, by binding to CCR2b, and by PPARγ-mediated inhibition of inflammation.