Lymphoproliferation, chronic B cell activation resulting in
hypergammaglobulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated
murine acquired immunodeficiency syndrome (
MAIDS). In vivo treatment of infected mice with recombinant
interleukin 12 (IL-12) beginning at the time of
infection or up to 9 wk after virus inoculation markedly inhibited the development of
splenomegaly and
lymphadenopathy, as well as B cell activation and Ig secretion. Treatment with
IL-12 also had major effects in preventing induction of several immune defects including impaired production of
interferon gamma (IFN-gamma) and
IL-2 and depressed proliferative responses to various stimuli. The
therapeutic effects of
IL-12 on the immune system of mice with
MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effects 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 induction and progression of
MAIDS are antagonized by
IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for developing treatments of retrovirus-induced
immune disorders with similar immunopathogenic mechanisms.