Interleukin 10 and interferon γ regulation of experimental Trypanosoma cruzi infection

Abstract

Studies were undertaken to determine whether interleukin 10, (IL-10) a cytokine shown to inhibit Interferon γ (IFN-γ) production, was involved in Trypanosoma cruzi infections in mice. Exogenous IFN-γ protects mice from fatal infection with T. cruzi. Furthermore, resistant B6D2 mice developed fatal T. cruzi infections when treated with neutralizing anti-IFN-γmonoclonal antibody (mAb). Thus, endogenous as well as exogenous IFN-γ is important in mediating resistance to this parasite. Because both T. crwzi-susceptible (B6) and -resistant (B6D2) mouse strains produced IFN-γ during acute infection, we looked for the concomitant production of mediators that could interfere with IFN-γ-mediated resistance to T. cruzi. We found that IL-10-specific mRNA was produced in the spleens of mice with acute T. cruzi infections. In addition, spleen cell culture supernatants from infected B6 mice, and to a lesser extent B6D2 mice, elaborated an inhibitor(s) of IFN-γ production. This inhibitor(s) was neutralized by anti-IL-10 mAb. These experiments demonstrated the production of biologically active IL-10 during T. cruzi infection. In further studies in vitro, it was shown that IL-10 blocked the ability of IFN-γto inhibit the intracellular replication of T. cruzi in mouse peritoneal macrophages. Thus, in addition to its known ability to inhibit the production of IFN-γ, IL-10 (cytokine synthesis inhibitory factor), may also inhibit the effects of IFN-γ. These experiments demonstrate that IL-10 is produced during infection with a protozoan parasite and suggest a regulatory role for this cytokine in the mediation of susceptibility to acute disease.