Blood mononuclear cell nitric oxide production and plasma cytokine levels in healthy Gabonese children with prior mild or severe malaria

Plasmodium falciparum malaria is an important cause of morbidity and mortal ity in children. Factors that determine the development of mild versus seve re malaria are not fully understood. Since host-derived nitric oxide (NO) h as antiplasmodial properties, we measured NO production and NO synthase (NO S) activity in peripheral blood mononuclear cells (PBMC) from healthy Gabon ese children,vith a history of prior mild malaria (PMM) or prior severe mal aria (PSM) caused by P. falciparum. The PMM group had significantly higher levels of NOS activity in freshly isolated PBMC and higher NO production an d NOS activity in cultured PBMC. The investigation of NO-modulating cytokin es (e.g., interleukin 12, gamma interferon, tumor necrosis factor alpha [TN F-alpha], and transforming growth factor beta 1) as an explanation for diff ering levels of NOS activity revealed that plasma levels of TNF-alpha were significantly higher in the PSM group. Our results suggest that NOS/NO and TNF-alpha are markers for prior disease severity and important determinants of resistance to malaria.