Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection.
Studies were undertaken to determine whether interleukin 10, (IL-10) a cytokine shown to inhibit interferon gamma (IFN-gamma) production, was involved in Trypanosoma cruzi infections in mice. Exogenous IFN-gamma protects mice from fatal infection with T. cruzi. Furthermore, resistant B6D2 mice developed fatal T. cruzi infections when treated with neutralizing anti-IFN-gamma monoclonal antibody (mAb). Thus, endogenous as well as exogenous IFN-gamma is important in mediating resistance to this parasite. Because both T. cruzi-susceptible (B6) and -resistant (B6D2) mouse strains produced IFN-gamma during acute infection, we looked for the concomitant production of mediators that could interfere with IFN-gamma-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-gamma 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-gamma to inhibit the intracellular replication of T. cruzi in mouse peritoneal macrophages. Thus, in addition to its known ability to inhibit the production of IFN-gamma, IL-10 (cytokine synthesis inhibitory factor), may also inhibit the effects of IFN-gamma. 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.
Silva
J S
JS
Seattle Biomedical Research Institute, Washington 98109.
Morrissey
P J
PJ
Grabstein
K H
KH
Mohler
K M
KM
Anderson
D
D
Reed
S G
SG
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology* / Q000517:prevention & control; D003433:Crosses, Genetic; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma