Tumour necrosis factor production in Falciparum malaria and its association with schizont rupture

To investigate the involvement of tumour necrosis factor (TNF) in human malaria, we studied TNF production in patients infected with Plasmodium falciparum, and in co-cultures of human mononuclear cells and malaria parasites in vitro. In the examined sample, plasma TNF levels of over 39 pg/ml were detected in the plasma of 59% of Gambian children with acute malaria, 17% of convalescents, 9% of children with mild infections other than malaria, and 7% of healthy Gambian adults. Mononuclear cells of acute malaria patients, when stimulated with endotoxin in vitro, secreted twice as much TNF as did those of convalescent individuals, and three times that of healthy adult controls. Erythrocytic cultures of P. falciparum stimulated increased TNF secretion by mononuclear cells from uninfected individuals, and a sharp rise in the rate of secretion occurred shortly after schizont rupture. We suggest that malaria fever is mediated, at least in part, through paroxysmal TNF release associated with schizont rupture.