Impaired Systemic Production of Prostaglandin E sub(2) in Children with Cerebral Malaria

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-PGE sub(2) (a stable end product of PGE sub(2) 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-PGE sub(2)/creatinine in children with varying clinical outcomes of CM. Among parasitemic children, those with asymptomatic parasitemia had the highest levels of bicyclo-PGE sub(2)/creatinine, whereas those with CM had significantly lower levels of bicyclo-PGE sub(2). Systemic levels of bicyclo-PGE sub(2)/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 PGE sub(2) is associated with adverse outcomes of CM, whereas elevated levels of PGE sub(2) in asymptomatic parasitemia suggest a potential role for PGs in protective immunity.