Nitric Oxide Production in Murine Leishmaniasis: Correlation of Progressive Infection with Increasing Systemic Synthesis of Nitric Oxide

Previous studies have shown that nitric oxide (NO) production is a major effector mechanism in the control of Leishmania major infection in the BALB/c and C3H murine models. The susceptibility of mice correlates with intrinsic NO production after infection. We have previously shown that blocking of systemic NO production with oral N-Omega-monomethyl-L-arginine results in decreased NO and exacerbated infection. The C3H mice also synthesize markedly more NO than BALB/c mice shortly after initial infection. We now show that late in infection, as the lesion size is increasing, the BALB/c NO production actually exceeds that seen during the curative stages of the C3H infection. In addition, treatment with meglumine antimoniate, which ameliorates but does not cure the BALB/c mouse, results in decreased systemic parasite load with a concomitant decrease in NO production. These results imply that in vivo, systemically measured levels of NO may in some circumstances reflect ongoing parasitic load, and that NO production is not always correlated with a curative response.