Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclooxygenase-2 with disease severity in children with Plasmodium falciparum malaria.
Prostaglandins (PGs) derived from inducible cyclooxygenase (COX)-2 are important proinflammatory mediators of the host-immune response to infection. Since the role of host-derived PG in human malaria is unknown, plasma bicyclo-PGE2 (a stable catabolite of PGE2), peripheral blood mononuclear cell COX-2 protein, and mRNA were measured in Gabonese children with and without malaria (n=129). Relative to healthy children, bicyclo-PGE2 and COX-2 protein were lower in children with mild (P=.007 and P=.026, respectively) and severe malaria (P=.002 and P=.010, respectively). COX-2 mRNA was also reduced in children with malaria. Investigation of COX-2 regulatory cytokines revealed an inverse correlation (P<.001) between plasma levels of bicyclo-PGE2 and interleukin (IL)-10, a cytokine that suppresses COX-2 expression. On the basis of these results, elevated PGE2 in healthy malaria-exposed children may protect against malaria, whereas IL-10-induced decreases in PGE2 during acute malaria may increase susceptibility to severe disease.
Perkins
D J
DJ
Department of Medicine, Veterans Affairs and Duke University Medical Centers, Durham, North Carolina 27705, USA. brice@acpub.duke.edu
Kremsner
P G
PG
Weinberg
J B
JB
D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000097:blood*; D018450:Disease Progression; D005681:Gabon; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007527:Isoenzymes / Q000032:analysis*; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D016753:Interleukin-10; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone