TRYPANOSOMA-CRUZI IS A POTENT INDUCER OF INTERLEUKIN-12 PRODUCTION INMACROPHAGES

Cytokines produced after infection with Trypanosoma cruzi have been sh own to be crucial in the determination of resistance or susceptibility . Interferon-gamma (IFN-gamma) is the predominant cytokine produced af ter infection and has been shown to protect susceptible mice from infe ction. IFN-gamma production by natural killer cells and T cells is ind uced by interleukin-12 (IL-12). Therefore, the aim of our study was to analyze the ability of T. cruzi to induce IL-12 production. Spleen ce lls and bone marrow-derived macrophages incubated with T. cruzi trypom astigotes induced high amounts of IL-12p40 mRNA as shown by reverse tr anscriptase-polymerase chain reaction. Lipopolysaccharide (LPS) was le ss efficient in inducing IL-12p40-specific mRNA. Furthermore, biologic ally active IL-12, detected by the capacity of the supernatant of infe cted macrophages to induce IFN-gamma production in spleen cells, was p roduced at very high levels. In comparison, macrophages stimulated wit h LPS secreted drastically less IL-12. Interestingly, only live, UV- o r gamma-irradiated trypanosomes, but not heat-killed parasites or lysa tes, were functional in this respect. In a kinetic study, in the super natant obtained from cultures of infected macrophages, IL-12 was alrea dy detectable at 2 h after infection, peaked at 32 h and declined afte r 45 h.