A protective role for endogenous tumor necrosis factor in Toxoplasma gondii infection

The involvement of tumor necrosis factor (TNF) in resistance to Toxoplasma gondii infection was examined by means of experiments in which mice were treated with anti-TNF antibodies prior to infection with ME49, a low-virulence Toxoplasma strain. In (BALB/cBy x C57BL/6J)F1 (CB6F1) mice, which are highly resistant to intraperitoneal (i.p.) infection with T. gondii ME49, 10(4) neutralizing units of anti-TNF caused a significant increase in trophozoite numbers in the peritoneal cavities of infected mice and transient signs of illness but no deaths. i.p. infection of anti-TNF-treated C57BL/6J (B6) mice, which are more susceptible to T. gondii and develop a chronic progressive toxoplasmosis, resulted in death for some of the mice. If the mice were infected perorally, however, and treated with anti-TNF, mortality was extensive in B6 mice but not in CB6F1 mice. Although it was not detected in their sera, TNF was found in the peritoneal fluids of i.p.-infected CB6F1 and B6 mice. Endogenously produced TNF thus appears to be an important mediator of resistance to T. gondii.