Induction of TNF in vitro as a model for the identification of toxic malaria antigens.

Tumour necrosis factor (TNF) has been implicated as a mediator of toxicity in a number of infectious diseases, including malaria. We have shown that human and rodent blood-stage parasites liberate heat-stable soluble antigens that induce the release of TNF by activated macrophages in vitro and in vivo, and are toxic to mice made hypersensitive to TNF by D-galactosamine. These antigens induce T-independent antibodies which specifically block their ability, but not that of bacterial lipopolysaccharide, to cause the secretion of TNF. Cytokine release in vitro may be a useful strategy for identifying potentially toxic molecules of infectious organisms and for investigating the nature of antibodies that can protect the host against their damaging effects.