Levels of tumour necrosis factor and soluble TNF receptors during malaria fever episodes in the community

The pyrogenic cytokine, tumour necrosis factor (TNF), is a mediator of malaria fever. Since high plasma levels of TNF are sometimes found in afebrile individuals with Plasmodium falciparum parasitaemia, it has been suggested that soluble forms of TNF receptors (sTNF-R55 and sTNF-R75) in the plasma may act to inhibit the pyrogenic effect of TNF. We have investigated plasma levels of TNF, sTNF-R55 and sTNF-R75 in relation to episodes of malaria fever detected in a cross-sectional study of 313 rural Gambian children during the malaria transmission season. Levels of TNF were significantly higher in the 20 children who had parasitaemia associated with fever than in 120 children who were afebrile despite malaria infection and 173 who had no detectable parasitaemia. In contrast, soluble TNF receptor levels did not differ between these clinical groups and, in a logistic regression model which included level of parasitaemia, we found TNF but not soluble TNF receptor levels to be associated with the presence of fever. These data support the role of TNF in malaria fever but suggest that soluble TNF receptors are not a major factor in modulating the fever.