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IL-12 attenuates bleomycin-induced pulmonary fibrosis
M P Keane1, J A Belperio, M D Burdick
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095-1922, USA. mpkeane@mednet.ucla.edu
Abstract:
Interleukin (IL)-12 is a potent inducer of interferon (IFN)-gamma. We postulated that IL-12 would attenuate bleomycin-induced pulmonary fibrosis. To test this hypothesis, we administered IL-12 or murine serum albumin to bleomycin-treated mice by daily intraperitoneal injection until day 12. Mice treated with IL-12 demonstrated decreased hydroxyproline levels compared with control treated mice. Furthermore, administration of IL-12 led to a time-dependent increase in both lung and bronchoalveolar lavage fluid IFN-gamma. The antifibrotic effect of IL-12 could be attenuated with simultaneous administration of neutralizing anti-IFN-gamma antibodies. These findings support the notion that IL-12 attenuates bleomycin-induced pulmonary fibrosis via modulation of IFN-gamma production.