IL-10 mediates susceptibility to Leishmania donovani infection

Human visceral leishmaniasis (VL) results in a severe and potentially fatal systemic disease, accompanied by cellular immune depression. The productio n of IL-10 correlates with ongoing disease and it has been suggested that t he cellular immune depression that accompanies active disease may be due to a predominance of IL-10 production rather than a lack of IFN-gamma product ion, which is essential for optimal macrophage activation and parasite elim ination. To examine the role of IL-10 in resistance during L. donovani infe ction (a causative agentof VL), the course of infection was examined in mic e lacking the gene for IL-10. BALB/c IL-10(-/-), as well as C57BL/6 IL-10(- /-) mice, were highly resistant to L. donovani infection, as evidenced by l iver parasite burdens which were tenfold lower than those in control mice a fter 14 days of infection. Enhanced resistance was accompanied by increased production of IFN-gamma and nitric oxide in BALB/c IL-10(-/-) mice. Suscep tibility to infection in BALB/c IL-10(-/-) mice was enhanced following in v ivo treatment with a neutralizing antibody to IFN-gamma or IL-12. Together these studies demonstrate for the first time that IL-10 is a critical compo nent of the immune response that inhibits resistance to L. donovani.