IL-4 Is Protective Against Development of Toxoplasmic Encephalitis

IFN-γ is critical for prevention of development of toxoplasmic encephalitis (TE). Since IL-4 down-regulates production of IFN-γ, we examined its role in the pathogenesis of TE in IL-4-targeted mutant (IL-4^-/-) mice. IL-4^-/- mice all died from 6 to 20 wk after peroral infection with cysts of the ME49 strain of Toxoplasma gondii; control mice survived. At 4 and 8 wk after infection, significantly greater numbers of T. gondii cysts and foci of acute inflammation, and greater amounts of tachyzoite-specific mRNA (by reverse-transcriptase PCR) were in brains of IL-4^-4- mice than controls. Toxoplasma IgG2b and IgC3 Ab levels were slightly but significantly higher in sera of IL-4^-/- than control mice, whereas IgM and IgG2a levels did not differ between these mice. Toxoplasma IgG1 and IgE Abs were not detected in sera of either strain. Amounts of IFN-γ, TNF-α, IL-6, and IL-10 mRNA detected by reverse-transcriptase PCR did not differ between brains of infected IL-4^-/- and controls, although brains of the former mice had greater numbers of inflammatory mononuclear cell infiltrates. IL-4 mRNA was detected only in infected control mice. Spleen cells of control mice at 8 wk after infection produced significantly greater amounts of IFN-y following stimulation in vitro with soluble T. gondii Ags than did those from IL-4^-/- mice. These results indicate that IL-4 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in the brain. The impaired ability of IL-4^-/- mice in the late stage of T. gondii infection to produce IFN-γ most likely contributes to their susceptibility for development of severe TE.