Cytokines associated with pathology in the brain tissue of fatal malaria.

Cytoadherence of Plasmodium falciparum-infected erythrocytes to the brain microvascular endothelial cells is believed to be an important cause of circulatory blockage in cerebral malaria. Cytokines released during acute infection may activate brain endothelial cells leading to increased binding of infected erythrocytes in the brain and reduced cerebral blood flow. This effect may be direct and more potent with the tissue-localized cytokines in the brain. In order to establish this relationship, brain tissues of cerebral and noncerebral malaria were compared. The most prominent histopathologic changes in the brain included edema, neuronal degeneration, ring hemorrhage, and percentage of parasitized erythrocytes sequestration were observed in cerebral malaria. Immunohistochemical staining of the brain sections demonstrated that tissue-localized TNF-alpha, IFN-gamma, IL-I1B, and IL-10 were associated with the histopathology. However, IL-4 was the only cytokine presented at moderate level in the brain tissue of noncerebral malaria which histopathology was the least. No tissue-localized cytokine was observed in the brain of P. vivax infection or of the car accident control cases.