IL-12 INDUCES IFN-GAMMA EXPRESSION AND SECRETION IN MOUSE PERITONEAL-MACROPHAGES

We previously reported that resting mouse peritoneal macrophages (PM) constitutively express low levels of IFN-gamma, whose production is co nsistently enhanced by exogenous IFN-gamma. In this study, we investig ated the effects of IL-12 on the replication of vesicular stomatitis v irus and on IFN-gamma gene expression in mouse PM. The addition of IL- 12 to freshly explanted PM resulted in the persistence of an antiviral state to vesicular stomatitis virus, while control PM progressively b ecame permissive for virus replication after 3 to 4 days in culture, T he IL-12-induced antiviral stale was inhibited by Abs to IFN-gamma, su ggesting that endogenous IFN-gamma was largely responsible for this an tiviral response, Moreover, IL-12 induced a consistent secretion of IF N-gamma, especially in cultured PM, The IL-12-induced antiviral state and IFN-gamma production were observed using PM from various strains o f mice, including LPS-defective C3H/HeJ, NK-deficient bg/bg DBA/2, Swi ss (CD1), and Swiss nude mice treated or not with anti-asialo GM(1) Ab s, A 4-h treatment with IL-12 was sufficient to induce a marked accumu lation of IFN-gamma mRNA, which was greater in cultured PM than in fre shly harvested cells. Lastly, immunofluorescence studies in IL-12-stim ulated macrophages clearly showed an enhancement of immunoreactive IFN -gamma compared with basal levels in cells exhibiting a macrophage (i. e., F4/80-positive) phenotype, Together, these findings demonstrate th at IL-12 can directly stimulate mouse PM to produce IFN-gamma. We sugg est that IL-12-induced IFN-gamma production by macrophages can play so me role in the generation of the antiviral and immunoregulatory effect s of IL-12.