Treatment with interleukin-12 (IL-12) induces leishmanicidal activity in experimental Leishmania donovani infection; therefore, BALB/c mice were injected with anti-IL-12 antibody to define the role of endogenous IL-12 in acquired resistance in this disseminated intracellular infection. Anti-IL-12 administration started 1 day after infection and given for 4 weeks abolished control of visceral parasite replication and in parallel suppressed endogenous interferon-gamma production and tissue granuloma assembly. Early (during week 1 only) and delayed treatment (during weeks 2-4 only) with anti-IL-12 also exacerbated visceral infection at week 4. These results point to a central role for endogenous IL-12 in acquired resistance to intracellular L. donovani and suggest that IL-12 is active in the cell-mediated immune response beyond the initial stage of host-parasite interaction.
