Cytokine profile suggesting that murine cerebral malaria is an encephalitis.

Cerebral malaria (CM) remains a poorly understood and life-threatening complication of malaria caused by the parasite Plasmodium falciparum. The discovery that murine CM caused by Plasmodium berghei ANKA and human CM are both characterized by production of inflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), led to a revival of the suggestion that P. berghei CM may have value as a model of the human disease. In this study, quantitative reverse transcription-PCR was used to measure levels of message for 18S rRNA of P. berghei and 10 cytokines in the brains, livers, and spleens of mice during the induction and course of CM. A coordinated increase in RNA of parasite and proinflammatory cytokines was observed in the brains of mice in parallel with onset of CM. Levels of message for parasite, TNF-alpha, and gamma interferon increased in the brains of mice from day 5 to death on day 7. These changes were observed only in the brain, and message for other cytokines remained near baseline levels. This demonstrated that parasite sequestration does take place in the brains of mice with CM. Histologically, CM was characterized by widespread damage to the microvasculature in the brain with focal infiltration of inflammatory cells. The pattern of cytokine production in the brain is characteristic of other murine encephalitides.