Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclooxygenase-2 with disease severity in children with Plasmodium falciparum malaria

J Infect Dis. 2001 Jan 1;183(1):113-8. doi: 10.1086/317660. Epub 2000 Nov 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Child
  • Child, Preschool
  • Cyclooxygenase 2
  • Dinoprostone / blood*
  • Disease Progression
  • Gabon
  • Humans
  • Interleukin-10 / blood
  • Isoenzymes / analysis*
  • Leukocytes, Mononuclear / enzymology*
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / immunology*
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / analysis*
  • RNA, Messenger / analysis

Substances

  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Interleukin-10
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone