Effects of age and parasitemia on nitric oxide production/leukocyte nitricoxide synthase type 2 expression in asymptomatic, malaria-exposed children

Age appears to influence not only the acquisition of clinical immunity to m alaria but also the susceptibility to and clinical manifestations of severe malaria. Asymptomatic malaria-exposed Tanzanian children have high product ion of nitric oxide (NO) and universal expression of leukocyte NO synthase type 2 (NOS2), which may protect against disease. To determine the effects of age and parasitemia on NO production, we measured urine and plasma NO me tabolites and leukocyte NOS2 expression in 45 fasting, asymptomatic, malari a-exposed children of different ages, stratifying parasitemia by thick film and polymerase chain reaction (PCR) analysis. Although NO production was s ignificantly higher in thick film-positive children than in thick film-nega tive children, after adjusting for age and gender, we were unable to detect a difference in NO production in thick film-negative children between thos e who were PCR positive and PCR negative. The relationship between age and NO production was determined using a generalized additive model adjusted fo r the effects of gender and parasitemia. Production of NO using all three m easures was highest in infancy, decreasing after the first year of life, an d then increasing again after 5 years of age. This pattern of age-related N O production is the reverse of the pattern of age-related morbidity from ce rebral malaria in coastal Tanzanian children. Elevated production of NO in both infants and older children may be related to age per se and malaria in fection respectively, and may be one of the mediators of the anti-disease i mmunity found most commonly in these two age groups.