INCREASED CONCENTRATIONS OF INTERLEUKIN-6 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST AND DECREASED CONCENTRATIONS OF BETA-2-GLYCOPROTEIN-I IN GAMBIAN CHILDREN WITH CEREBRAL MALARIA

To investigate the pathogenic versus the protective role of cytokines and toxin-binding factors in Plasmodium falciparum infections, we meas ured the concentrations of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, and IL-6, as well as soluble receptors of tumor necrosis factor and IL-6 (sIL-6R) i n serum of Gambian children with cerebral malaria, mild or asymptomati c malaria, or other illnesses unrelated to malaria. Because cytokine s ecretion may be triggered by toxic structures containing phosphatidyli nositol (PI), we also measured concentrations of anti-PI antibodies an d the PI-binding serum protein beta-2-glycoprotein I. We found increas ed concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M a ntibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We conclud e that increased concentrations of cytokines and soluble cytokine rece ptors represent a normal host response to P. falciparum infections but that excessive secretion of cytokines like IL-6 may predispose to cer ebral malaria and a fatal outcome white beta-2-glycoprotein I may pref ect against a fatal outcome of cerebral malaria.