Role of TNF and ICAM-1 in the development of experimental murine cerebral malaria

Cerebral malaria (CM) is a major cause of morbidity and mortality in Africa, especially in children. The pathological feature is a dense sequestration of parasitized erythrocytes in cerebral blood vessels. It was postulated that TNF may be an important factor in the pathogenesis of this condition, since children with cerebral malaria have high circulating TNF levels. Experimental evidence for this hypothesis comes from Plasmodium berghei ANKA (PbA) infection in the genetically susceptible CBNca mice, which at least in part mirrors clinical CM. In the experimental model, CM is associated with elevated blood TNF levels. The administration of neutralising antibodies and of inhibitors of TNF synthesis prevent CM in mice. TNF antibodies reduced fever associated with clinical CM.