Genetically resistant mice lacking IL-18 gene develop Th1 response and control cutaneous Leishmania major infection

IL-18 has been shown to play a critical role in the development of a Th1 re sponse and immunity against intracellular pathogens. To determine the role of IL-18 in the development of protective immunity against Leishmania major ,we have analyzed the course of cutaneous L. major in IL-18-deficient C57BL /6 mice (IL-18(-/-)) compared with similarly infected wild-type mice (IL-18 (+/+)). After L. major infection, IL-18(-/-) mice may develop larger lesion s during eariy phase of infection,but eventually will resolve them as effic iently as IL-18(+/+) mice. By 2 wk after infection, although Ag-stimulated lymph nude cells from L. major-infected IL-18(+/+) and IL-18(-/-) mice prod uced similar levels of IFN-gamma, those from IL-18(-/-) mice produced signi ficantly more IL-12 and IL-4, By 10 wk after infection, both IL-18(+/+) and IL-18(-/-) mice had resolved L. major infection, At this time, lymph node cells from both IL-18(+/+) and IL-18(-/-) mice produced IL-12 and IFN-gamma but no IL-4, Furthermore, administration of anti-IFN-gamma Abs to IL-18(-/ -) mice rendered them susceptible to L. major. These results indicate that despite the role IL-18 may play in early control of cutaneous L. major lesi on growth, this cytokine is not critical for development of protective Thl response and resolution of L. major infection.