IN-VIVO TREATMENT WITH INTERLEUKIN-12 PROTECTS MICE FROM IMMUNE ABNORMALITIES OBSERVED DURING MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME (MAIDS)

Lymphoproliferation, chronic B cell activation resulting in hypergamma globulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated murine acquired immunodeficie ncy syndrome (MAIDS). In vivo treatment of infected mice with recombin ant interleukin 12 (IL-12) beginning at the time of infection or up to 9 wk after virus inoculation markedly inhibited the development of sp lenomegaly and lymphadenopathy, as well as B cell activation and Ig se cretion. Treatment with IL-12 also had major effects in preventing ind uction of several immune defects including impaired production of inte rferon gamma (IFN-gamma) and IL-2 and depressed proliferative response s to various stimuli. The therapeutic effects of IL-12 on the immune s ystem of mice with MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effec ts on expression of ecotropic MuLV. IL-12 treatment was not effective in IFN-gamma knockout mice or in infected mice treated simultaneously with IL-12 and anti-IFN-gamma. These results demonstrate that inductio n and progression of MAIDS are antagonized by IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for dev eloping treatments of retrovirus-induced immune disorders with similar immunopathogenic mechanisms.