The prognostic and pathophysiologic role of pro- and anti-inflammatory cytokines in severe malaria

Pro- and antiin¯ammatory cytokines were measured on admission in 287 consecutive Vietnamese adults with severe falciparum malaria. Plasma interleukin (IL)±6, IL-10, and tumor necrosis factor (TNF)±a concentrations and the IL-6: IL-10 ratio were signi®cantly higher in patients who died than in survivors (). On multivariate analysis, hyperparasitemia,P!.001 jaundice, and shock were all associated independently with raised IL-6, IL-10, and interferon-g, and acute renal failure speci®cally with raised TNF-a levels. Cerebral malaria patients, particularly those without other vital organ dysfunction, had signi®cantly lower levels of these cytokines (), re¯ecting a more localized pathology. Serial IL-6 and IL-10 measurementsP =.006 made on 43 patients who died and matched survivors indicated a relative de®ciency in IL-10 production as death approached. Elevated plasma cytokines in severe malaria are associated with systemic pathologic abnormalities, not cerebral involvement. Both the overall magnitude of the cytokine responses and the eventual imbalance between the pro- and antiin¯ammatory responses are important determinants of mortality. Malaria remains a major cause of morbidity and mortality throughout much of the tropical world. The manifestations o