Tumor necrosis factor in malaria-induced abortion

The cause of fetal loss in malaria is not known. We report that a small (1.5-5.0 micrograms) intravenous dose of recombinant human tumor necrosis factor (TNF) caused fetal death and abortion in 16 day pregnant mice that were carrying low densities of Plasmodium vinckei. In contrast, 50 micrograms human TNF did not cause fetal death or abortion in uninfected 16 day pregnant mice. Endogenous TNF, which was not detectable in plasma of low parasitemia animals, pregnant or not, was present (1.6 +/- 0.9 ng/ml) in samples from malarial pregnant mice when, on day 17, parasitemia was high and the first signs of impending abortion were evident. No TNF was detectable in the plasma of uninfected mice at day 17 of pregnancy. A small dose of TNF also caused fetal death in 16 day pregnant mice that had received an intravenous injection of Coxiella burneti extract 9-10 days earlier. Thus, TNF-induced abortion may occur in a range of infections in which systemic macrophage activation occurs and a trigger for TNF release is present.