IL-12 attenuates bleomycin-induced pulmonary fibrosis.
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.
Keane
M P
MP
Division 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
Belperio
J A
JA
Burdick
M D
MD
Strieter
R M
RM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D000906:Antibodies; D001761:Bleomycin; D018664:Interleukin-12; D007371:Interferon-gamma; D006909:Hydroxyproline