Effect of Nilotinib on Bleomycin-Induced Acute Lung Injury and Pulmonary Fibrosis in Mice

Background: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. Objectives: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. Methods: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. Results: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1 and tumor necrosis factor were decreased in the imatinib and Received: April 6, 2010 Accepted after revision: March 18, 2011 Published online: June 9, 2011 Jin Woo Kim Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital , 65-1 Keumho Dong Uijeongbu City , Kyungki Province 480-717 (Korea) Tel. +82 31 820 3995, E-Mail medkjw @ catholic.ac.kr © 2011 S. Karger AG, Basel 0025–7931/11/0823–0273$38.00/0 Accessible online at: www.karger.com/res D ow nl oa de d by : 54 .7 0. 40 .1 1 10 /2 4/ 20 17 7 :1 0: 52 P M