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Am J Physiol Lung Cell Mol Physiol 281: L92-L97, 2001;
1040-0605/01 $5.00
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Vol. 281, Issue 1, L92-L97, July 2001

IL-12 attenuates bleomycin-induced pulmonary fibrosis

Michael P. Keane, John A. Belperio, Marie D. Burdick, and Robert M. Strieter

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095-1922

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.

lung; chemokines; inflammation; in vivo animal models


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