Impaired systemic production of prostaglandin E2 in children with cerebral malaria.

Abstract

Prostaglandins (PGs) are important mediators of macrophage activity, vascular permeability, fever, erythropoiesis, and proinflammatory responses to infection. Our recent studies have shown that plasma levels of bicyclo-PGE2 (a stable end product of PGE2 metabolism) and leukocyte cyclooxygenase (COX)-2 gene expression are suppressed in children with malarial anemia. Since the role of PGs as immunomodulators of human cerebral malaria (CM) has not been examined, we investigated urinary levels of bicyclo-PGE2/creatinine in children with varying clinical outcomes of CM. Among parasitemic children, those with asymptomatic parasitemia had the highest levels of bicyclo-PGE2/creatinine, whereas those with CM had significantly lower levels of bicyclo-PGE2. Systemic levels of bicyclo-PGE2/creatinine were not significantly associated with parasitemia, hemoglobin levels, or levels of the PG-regulatory cytokine tumor necrosis factor- alpha but were positively correlated with levels of interleukin-10. The results presented here show that impaired systemic production of PGE2 is associated with adverse outcomes of CM, whereas elevated levels of PGE2 in asymptomatic parasitemia suggest a potential role for PGs in protective immunity.

• Authors: Douglas J Perkins, James B Hittner, Esther D Mwaikambo, Donald L Granger, J Brice Weinberg, Nicholas M Anstey
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 191 Issue 9 Pg. 1548-57 (May 01 2005) ISSN: 0022-1899 [Print] United States
• PMID: 15809915 (Publication Type: Clinical Conference, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hemoglobins
• Membrane Proteins
• Tumor Necrosis Factor-alpha
• Creatinine
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• Child, Preschool
• Creatinine (urine)
• Cyclooxygenase 2
• Dinoprostone (biosynthesis)
• Gene Expression Regulation, Enzymologic
• Hemoglobins (metabolism)
• Humans
• Malaria, Cerebral (blood, enzymology, genetics, physiopathology)
• Membrane Proteins
• Prostaglandin-Endoperoxide Synthases (genetics)
• Tanzania
• Tumor Necrosis Factor-alpha (metabolism)