Human macrophage tumor necrosis factor (TNF)-alpha production induced by Trypanosoma brucei gambiense and the role of TNF-alpha in parasite control

Trypanosoma brucei gambiense, a causative agent of sleeping sickness, induc ed a dose-dependent production of tumor necrosis factor (TNF)-alpha by huma n macrophages in vitro. TNF-alpha was also induced in the Mono Mac 6 cell l ine, which indicates a direct effect of parasite components on macrophages. Parasite-soluble factors were also potent inducers of TNF-alpha. The addit ion of anti-TNF-alpha to cocultures of macrophages and parasites increased the number of trypanosomes and their life span, whereas irrelevant antibodi es had no effect. TNF-alpha may have a direct role (i.e., direct trypanolyt ic activity) and/or an indirect one, such as TNF alpha -mediated induction of cytotoxic molecules. A direct dose-dependent lytic effect of TNF-alpha o n purified parasites was observed. This lytic effect was inhibited by anti- TNF-alpha. These data suggest that, as in experimental trypanosomiasis, TNF -alpha is involved in parasite growth control in human African trypanosomia sis.