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

Intravascular sequestration and altered cytokine expression patterns are ke y determinators of CNS lesion formation in patients with cerebral malaria ( CM). Among others, altered prostaglandin concentrations were revealed by cl inical trials in peripheral blood of CM patients. Prostaglandin synthesis i s controlled by cyclooxygenases (COX, prostaglandin endoperoxide synthase, PGG/H synthase) and COX expression has been attributed a key role in immuno modulation, 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 expe riments were used to verify the cellular identity of COX-1 and COX-2 expres sing cells. Compared to healthy controls, significant (P=0.0006) accumulati on of COX-1 expressing macrophages/microglial cells was detected in Durck'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 paren chyma. 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. (C) 2000 Published by Elsevier Science B.V. All rights reserved.