Endogenous interferon-gamma, macrophage activation, and murine host defense against acute infection with Trypanosoma...

Parenteral interferon-gamma (IFN-gamma) activates murine macrophages to inhibit Trypanosoma cruzi multiplication and diminishes parasitemia and mortality in acute infection. To investigate the role of endogenous IFN-gamma in acute infection, monoclonal antibody to IFN-gamma was injected intraperitoneally into mice. The 6250 neutralizing units given 24 and 96 h after infection reproducibly increased mortality (P less than .05). Histology sections showed markedly more nests of T. cruzi in treated mice. BALB/c, Swiss Webster, C57Bl/6, and C3H/HEN mice were susceptible to the effects of anti-IFN-gamma. Peritoneal macrophages from mice 4 days after infection and a single dose of 6250 units of anti-IFN-gamma had significantly reduced ability to inhibit T. cruzi multiplication. Multiple doses of anti-IFN-gamma delayed but did not prevent macrophage activation. These results indicate the critical role of endogenous IFN-gamma for macrophage activation and host defense against acute T. cruzi infection in mice.