Phospholipid-containing Toxic Malaria Antigens Induce Hypoglycaemia

Hypoglycaemia is associated with severe malaria and is an important prognostic indicator. Molecules liberated during overnight incubation of erythrocytes infected with Plasmodium yoelii induce marked hypoglycaemia in normal mice, with a delayed time course compared with insulin; some, though weaker, activity could also be obtained by overnight incubation of uninfected erythrocytes. The active component shares many properties with the phospholipid-containing molecules which we have previously shown to be toxic and to induce the release of tumour necrosis factor (TNF) from macrophages. However a MoAb which neutralizes the cytotoxicity of tumour necrosis factor in vitro did not prevent this induction of hypoglycaemia, whereas antiserum against the toxic antigens did, as did immunization of normal (but not the immunoglobulin-deficient SCID) mice with the same material. Furthermore, normal mice injected with the antigens after immunization with phosphatidyl inositol or inositol monophosphate did not develop hypoglycaemia; the latter compound was also inhibitory when mixed with the antigens before injection. These compounds were previously shown to block the induction of TNF by the antigens and to induce the production of inhibitory antibodies. The role of these molecules in the etiology of the hypoglycaemia of malaria is discussed.