Interleukin (IL)-12 is a potent inducer of interferon (IFN)-gamma. We postu
lated that IL-12 would attenuate bleomycin-induced pulmonary fibrosis. To t
est this hypothesis, we administered IL-12 or murine serum albumin to bleom
ycin-treated mice by daily intraperitoneal injection until day 12. Mice tre
ated with IL-12 demonstrated decreased hydroxyproline levels compared with
control treated mice. Furthermore, administration of IL-12 led to a time-de
pendent increase in both lung and bronchoalveolar lavage fluid IFN-gamma. T
he antifibrotic effect of IL-12 could be attenuated with simultaneous admin
istration 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.