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

Prostaglandins (PGs) derived from inducible cyclooxygenase (COX)-2 are impo rtant proinflammatory mediators of the host-immune response to infection. S ince the role of host-derived PG in human malaria is unknown, plasma bicycl o-PGE(2) (a stable catabolite of PGE(2)), peripheral blood mononuclear cell COX-2 protein, and mRNA were measured in Gabonese children with and withou t malaria (n=129). Relative to healthy children, bicyclo-PGE(2) and COX-2 p rotein were lower in children with mild (P=.007 and P=.026, respectively) a nd severe malaria (P=.002 and P=.010, respectively). COX-2 mRNA was also re duced in children with malaria. Investigation of COX-2 regulatory cytokines revealed an inverse correlation (P<.001) between plasma levels of bicyclo- PGE(2) and interleukin (IL)-10, a cytokine that suppresses COX-2 expression . On the basis of these results, elevated PGE(2) in healthy malaria-exposed children may protect against malaria, whereas IL-10-induced decreases in P GE(2) during acute malaria may increase susceptibility to severe disease.