Ameliorating effect of murine interferon gamma on bleomycin-induced lung collagen fibrosis in mice

Fibrotic lung diseases are characterized by accumulation of collagen in the lung (1). These diseases generally respond poorly to drug therapy (1). A variety of chemicals have been tested in different experimental models of lung fibrosis to ameliorate or prevent the development of fibrosis (2-4). In this regard, intratracheal instillation of bleomycin, an antineoplastic drug, is often employed to produce experimental models of lung fibrosis in hamsters (5,6), rats (7,8), and mice (9). Using the bleomycin model of lung fibrosis, we and others have tested the ability of various compounds to prevent lung fibrosis (5,7, 10,11). It is unfortunate that these compounds were not satisfactory, since they produced systemic toxicity and lacked specificity in inhibiting collagen biosynthesis. Regulation of collagen metabolism is not completely understood. However, it is generally believed that the immune system and inflammatory conditions affect the metabolic functions of the fibroblasts responsible for collagen synthesis and deposition (12). Recently Rosenbloom et al. (13) have demonstrated that interferon gamma had a potent inhibitory effect on collagen synthesis by cultured human diploid fibrolasts. The inhibitory effect was attributed to a reduction in the levels of collagen mRNA. In the present paper we report that the administration of recombinant murine interferon gamma (IFN-γ) caused a significant reduction in the accumulation of collagen in the lungs of bleomycin-treated mice.