IL-12 gene-deficient C57BL/6 mice are susceptible to Leishmania donovani but have diminished hepatic immunopathology

To determine the in vivo role of IL-12 in the development of protective imm unity in visceral leishmaniasis caused by Leishmania donovani, we examined the course of L. donovani infection in IL-12-deficient C57BL/6 (IL-12(-/-)) mice. IL-12(-/-) mice displayed significantly higher parasite burdens in t heir livers and spleens than wild-type C57BL/6 mice throughout the course o f infection. Despite high parasite burdens, the onset of hepatosplenomegaly was significantly delayed in L. donovani-infected IL-12(-/-). Moreover, li vers and spleens from IL-12(-/-) mice displayed significantly less inflamma tion and poorly formed granulomatous lesions than those from IL-12(+/+) mic e throughout the course of infection, Antigen-stimulated splenocytes from I L-12(-/-) mice produced significantly less lFN-gamma but more IL-4 than IL- 12(+/+) mice. These findings indicate that although endogenous IL-12 is cri tical for the development of protective immunity to L. donovani, it is also responsible for inducing the significant immunopathology associated with v isceral leishmaniasis.