Interleukin‐12 Regulates the Response to Chemotherapy in Experimental Visceral Leishmaniasis

Publisher Website
Google Scholar
Abstract
In experimental visceral leishmaniasis, interleukin (IL)—12 initiates control over Leishmania donovani via Th1 cell activation, interferon (IFN)—γ secretion, and granuloma formation. Because the leishmanicidal effect of conventional therapy, pentavalent antimony (Sb), also requires T cells and endogenous IFN-γ, we tested IL-12 as a determinant of host responsiveness to chemotherapy. L. donovani—challenged IL-12p35 gene knockout (KO) mice permitted uncontrolled hepatic infection and failed to respond to Sb. In contrast, 96% of liver parasites in KO mice were killed by amphotericin B, which acts independently of immune responses. Exogenous IL-12 combined with Sb was tested in normal mice: low-dose Sb was converted from weakly to strongly leishmanicidal, and a no-effect Sb dose was converted to ∼100% leishmanistatic. IL-12 plus Sb synergism in normal mice was IFN-γ dependent; however, IL-12 also increased responsiveness to Sb in IFN-γ KO mice. Thus, IL-12 regulates host IFN-γ—dependent and —independent responses that permit and/or enhance the leishmanicidal activity of Sb.

This publication has 0 references indexed in Scilit: