Abstract:
Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium fakiparum
in vitro. It has been hypothesized, however, that excess NO production contributes to
the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO
production [urinary and plasma nitrate + nitrite (NO~)], leukocyte-inducible nitric oxide synthase
type 2 (NOS2), and plasma TNF-c~ and IL-10 levels with disease severity in 191 Tanzanian
children with and without malaria. Urine NO• excretion and plasma NOx levels (corrected
for renal impairment) were inversely related to disease severity, with levels highest in
subclinical infection and lowest in fatal cerebral malaria. Results could not be explained by differences
in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine
known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen
was detectable in all control children tested and in all those with subclinical infection, but was
undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in
cerebral malaria may contribute to pathogenesis. In contrast, high fasting NO x levels and leukocyte
NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis
might protect against clinical disease. NO appears to have a protective rather than pathological
role in African children with malaria.