Phospholipid-containing toxic malaria antigens induce hypoglycaemia

Abstract

SUMMARY Hypoglycaemia is associated with severe malaria and is an important prognostic indicator. Molecules liberated during overnight incubation of erythrocytcs infected with Plasmodium yoelii induce marked hypoglycaemia in normal mice, with a delayed lime course compared with insulin: some, though weaker, activity could also be obtained by overnight incubation of uninfected crythrocytes. The active component shares many properties with (he 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 antiscrum 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 monophosphale 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 inhibilory antibodies. The role of these molecules in the etiology of the hypoglycaemia of malaria is discussed.