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* Department of Immunology, George Washington University Medical Center, Washington, DC 20037; and
Laboratory of Parasitic Diseases and
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
The roles of IL-10 and IL-4 receptor signaling were evaluated in a murine model of Leishmania major infection. In previous studies the L. major substrain LV39 caused progressive, nonhealing lesions in BALB/c mice deficient for IL-4R 
-chain (IL-4R), while substrain IR173 was highly controlled. To explore whether IL-10 is responsible for inducing susceptibility to LV39, wild-type and IL-4R-/- mice were treated with anti-IL-10R mAb, and in a genetic approach, the IL-4R-/- mice were crossed with BALB/c IL-10-/- mice. In contrast to the lack of resistance conferred by IL-4R gene deletion, partial resistance to LV39 was conferred by IL-10 gene deletion or treatment of BALB/c mice with anti-IL-10R mAb. Lesion sizes and LV39 parasite numbers were further and dramatically reduced in both anti-IL-10R-treated IL-4R-/- mice and IL-4R x IL-10 double knockouts. Anti-IL-10R mAb treatment further suppressed parasite growth in IL-4R-/- mice infected with L. major IR173. Production of IFN-
was only increased relative to wild-type or littermate controls in IL-4R-/- mice with complementary defects in IL-10. Comparisons of IFN--treated infected macrophages in vitro indicated that LV39 required 25- to 500-fold greater concentrations of IFN- than IR173-infected macrophages to achieve a similar efficiency of parasite killing. These studies suggest that regardless of parasite substrain, IL-10 is as important as IL-4/IL-13 in promoting susceptibility to L. major and even more so for those substrains that are relatively resistant to IFN- mediated killing.
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