PREVENTION OF EXPERIMENTAL CEREBRAL MALARIA BY ANTICYTOKINE ANTIBODIES Interleukin 3 and Granulocyte Macrophage Colony-stimulating Factor Are Intermediates in Increased Tumor Necrosis Factor Production and BY GEORGES E. GRAD, VINCENT KINDLER, PIERRE-FRANCOIS PIGUET,

Recent studies have shown that TNF/cachectin, a cytokine mostly released by activated macrophages, plays a central role in experimental cerebral malaria (CM), an acute and lethal neurological syndrome that follows infection by Plasmodium berghei ANKA strain in mice (1) . This experimental syndrome reproduces some of the features of human cerebral malaria, the most severe complication of P. falciparum infection in man . Experimental CM appears to represent a strictly T cell-dependent immunopathological complication of P. berghei infection, since the functional integrity of CD4+ T lymphocytes is required for the neurological syndrome to occur (2) . IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are two cytokines released by activated T cells that stimulate the growth and differentiation of various hemopoietic cell lines, among which are macrophages (3-5) . This work explores the possible role of these cytokines as intermediates in the marked TNF release leading to CM .