Abstract

Cerebral malaria (CM) is a major life-threatening complication of Plasmodium falciparum infection. The nature of the pathogenetic processes leading to the cerebral complications is poorly understood. Mouse models of this condition have provided insight into the key events in pathogenesis, including those that occur before clinical symptoms are seen. Some T helper 1 (Th1) cytokines (e.g. interferon-gamma, lymphotoxin and tumour necrosis factor) have been implicated in driving the immunopathological process leading to CM, whereas some Th2 cytokines (e.g. interleukin-10, transforming growth factor-beta) appear to oppose this process. Upregulation of leukocyte adhesion molecules on the cerebral microvascular endothelium appears to be an important component of the proinflammatory actions of the cytokines. Activation of platelets in the cerebral microcirculation could also be a key event in CM. Furthermore, recent evidence has emerged indicating that cytokines might influence biochemical pathways in the brain that, in turn, could determine the outcome of CM.