IFLN-GAMMA IS NOT REQUIRED IN THE IL-12 RESPONSE TO VESICULAR STOMATITIS-VIRUS INFECTION OF THE OLFACTORY-BULB

In this report, the role of IFN-gamma in host defense to exogenous IL- 12 and clearance of vesicular stomatitis virus (VSV) from the central nervous system was examined, Wild-type and IFN-gamma knockout mice inf ected with VSV were treated with IL-12 or medium. In both groups, IL-1 2 treatment resulted in 1) substantially decreased VSV titers in brain homogenates and diminished immunohistochemical detection of VSV Ags i n tissue sections; 2) induction of types 1, 2, and 3 nitric oxide synt hase; and 3) induction of MHC molecules and rapid infiltration of bath T cells and NK cells, These results suggest that IFN-gamma production , both systemically and in the olfactory bulb, contributes to but is n ot essential for clearance of VSV from the brain, Neutralization of TN F-alpha in IFN-gamma knockout mice mice treated with IL-12 was accompa nied by the same immunohistochemical changes, implying that neither IF N-gamma nor TNF-alpha was required. In vitro studies using purified IL -12 or IFN-gamma in culture medium induced nitric oxide synthase isofo rms in neurons, glia, and macrophages, and MHC II on glia and macropha ges. These data suggest that IL-12 directly activates neurons to promo te viral clearance in vivo.