Malarial parasites induce TNF production by macrophages.

Mouse peritoneal macrophages incubated with erythrocytes infected with non-lethal or lethal variants of Plasmodium yoelii or with P. berghei, in the presence of polymyxin B to exclude the effects of any contaminating endotoxin, secreted a cytotoxic factor into the supernatant that was shown to be tumour necrosis factor (TNF). No differences were observed in the ability of the three types of parasite to induce TNF production, which was maximal in the range of 0.2-5 infected erythrocytes per macrophages. TNF production was equivalent to that induced by lipopolysaccharide (LPS) and was enhanced by pretreatment of the macrophages with interferon-gamma (IFN-gamma) or with indomethacin. Culture media containing parasite products also induced macrophages to secrete TNF. The activity withstood boiling and was inhibited by malaria-specific antisera. Since heat-stable antigens are present in the circulation of patients with malaria, they may induced the secretion of TNF, a mediator of endotoxic shock, which could contribute to the pathology of the disease.