BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN THE RAT - INHIBITION BY INDOMETHACIN

Abstract

A model for pulmonary fibrosis in the rat was developed using intratracheal bleomycin administration. The histopathologic features of the reaction are similar to those reported in the hamster model. Increases in vascular permeability are seen in the lung within 24 h and persist over a 2 mo. period. Extractable collagen, as measured by hydroxyproline, increases during this time by a factor > 1.5 times the reference control values of normal lung. During this same period, a prominent eosinophilia develops. The continued treatment of bleomycin-injected rats with indomethacin markedly diminishes the amount of extractable lung collagen at 60 days and the histopathologic evidence of pulmonary fibrosis. The eosinophilia over the first 3 wk is also markedly suppressed. Less dramatic effects were seen with the permeability changes. These findings indicate that the rat is a reliable and useful model for the study of bleomycin-induced pulmonary fibrosis and that treatment with indomethacin ameliorates the lung changes. Bleomycin is an antineoplastic agent which is a well-known cause of pulmonary fibrosis in humans.