RESISTANCE TO TRYPANOSOMA-CRUZI INFECTION IN MICE DOES NOT NECESSARILY CORRELATE WITH PRODUCTION OF INTERFERON-GAMMA IN-VIVO

Interferon-gamma (IFN-gamma) is the most important mediator of inhibit ion of intracellular replication of Trypanosoma cruzi in vitro and has a protective effect against this parasite if administered in vivo. He re we have analyzed the importance of IFN-gamma for resistance against a lethal infection with I cruzi in a mouse model system. Resistant B6 D2 mice survived the infection with a virulent strain of I: cruzi, whe reas susceptible BALB/c mice died within 3 weeks. Both strains produce d large amounts of IFN-gamma after infection. Surprisingly, susceptibl e mice had higher serum concentrations of IFN-gamma and showed, using in situ hybridization a stronger increase in IFN-gamma mRNA-producing cells in their spleens than resistant mice. Moreover, this pattern was also found when immune spleen cells were stimulated with parasite ant igens in vitro. However, a marked difference between these mice was fo und in the production of IL-4, which was much higher in susceptible mi ce in vivo and in vitro. No difference was found for IL-10. These data show that, at least in the mouse strain/parasite combination used, pr oduction of IFN-gamma is not the decisive factor determining resistanc e or susceptibility to T. cruzi. Rather, it is possible that the balan ce between protective (e.g., IFN-gamma) and exacerbative cytokines (e. g., IL-4) may decide over disease control or progression.