Mouse macrophages infected with Trypanosoma cruzi in vitro may be activated to reduce
parasite infection by
interferon gamma (IFN-gamma). The addition of up to 10,000 units of IFN-gamma however, does not result in a 100% reduction of intracellular parasites. We, therefore, investigated the possibility that macrophages require an additional signal or signals to completely clear T. cruzi
infection. Because the combination of IFN-gamma with
lipopolysaccharide greatly enhanced macrophages ability to decrease the number of intracellular parasites, the interaction of IFN-gamma with
tumor necrosis factor (TNF) was examined. TNF alone and the combination of TNF with IFN-gamma did not have a significant effect on reducing parasite numbers below that obtained with IFN-gamma alone. This was also true for
lymphotoxin, a lymphokine similar to TNF in structure and function. The effect of IFN-gamma in combination with a
cytokine-rich supernatant containing
IL-2,
IL-3,
IL-4,
IL-5, and IFN-gamma on macrophage clearance of the parasite was also examined. The
cytokine-rich supernatant alone had no effect on reducing
parasite infection of the macrophages; indeed, in some experiments the addition of the supernatant resulted in an increase in the level of
parasite infection. However, 1000 units of IFN-gamma combined with the complex
cytokine mixture caused a decrease in
parasite infection of nearly 100% compared to that of control cultures treated with media alone. To determine which
cytokine or
cytokines in the supernatant were responsible for this synergistic activity, anti-
cytokine antibodies were added to the supernatant prior to its addition with IFN-gamma to the cultures. Anti-IL-4 was the only antibody found to inhibit the synergism of IFN-gamma with the
cytokine-rich supernatant.
IL-4, however, did not significantly enhance the ability of IFN-gamma to induce macrophage clearance of the parasite, and
IL-4 alone caused a slight increase in
parasite infection in vitro. These results further define the role that
cytokines play in T. cruzi
infection of macrophages in vitro and suggest that the interaction of
cytokine networks within this system is complex.