MODULATION OF MURINE AIDS-RELATED PATHOLOGY BY CONCURRENT ANTIBODY TREATMENT AND COINFECTION WITH LEISHMANIA-MAJOR

Infection of C57BL/6 mice with a mixture of murine leukemia viruses (M uLVs) designated LP-BM5 MuLV leads to a disease characterized by progr essive immunodeficiency and lymphoproliferation, known as murine AIDS (MAIDS), The development of MAIDS is associated with increased B-cell lymphoblast proliferation, but there is reason to believe that T-cell function and, particularly, T-cell-derived cytokines may also play a r ole. We have previously shown that concurrent infection with Leishmani a major (which induces a strongly polarized Th1 response in C57BL/6 mi ce) and LP-BM5 MuLV modulates the disease induced by both infections, Here we show by treatment of mice with anticytokine antibodies that th is modulation is largely exerted through the balance of Th1 and Th2 cy tokines. Infected mice treated with antibodies to interleukin-4 and in terleukin-10 exhibited a delayed development of MAIDS-related patholog y and maintained T-cell responsiveness longer than mice treated with c ontrol antibody. Gamma interferon induced by coinfection with L. major synergized with anti-IL-4 treatment to inhibit the development of MAI DS pathology, Conversely, treatment with anti-gamma interferon led to a significant increase in splenomegaly and lymphadenopathy and slightl y exacerbated loss of T-cell function, These data suggest that the pro duction of Th2-associated cytokines may promote MAIDS pathology, while Th1-associated cytokines may help control the disease.