Focal accumulation of cyclooxygenase-1 (COX-1) and COX-2 expressing cells in cerebral malaria.

Intravascular sequestration and altered cytokine expression patterns are key determinators of CNS lesion formation in patients with cerebral malaria (CM). Among others, altered prostaglandin concentrations were revealed by clinical trials in peripheral blood of CM patients. Prostaglandin synthesis is controlled by cyclooxygenases (COX, prostaglandin endoperoxide synthase, PGG/H synthase) and COX expression has been attributed a key role in immunomodulation, hemostasis and inflammation in a wide variety of pathologically altered brain tissues. We have now analyzed expression of COX-1 and COX-2 in brains of patients with CM by immunohistochemistry. Double labeling experiments were used to verify the cellular identity of COX-1 and COX-2 expressing cells. Compared to healthy controls, significant (P=0.0006) accumulation of COX-1 expressing macrophages/microglial cells was detected in Dürck's granulomas. Accumulations of COX-2 expressing endothelial cells (P=0.0006) and COX-2 expressing astrocytes (P=0.0012) were detected in CM brain parenchyma. The restricted expression and accumulation of COX-1 and COX-2 in CM brains adds convincing evidence for the participation of cyclooxygenases in the formation of fever, inflammation and granuloma in these patients.