Nitric oxide and reactive nitrogen intermediates during lethal and nonlethal strains of murine malaria

The virulence of Plasmodia depends partly on the strain of parasite and par tly on the host. In this study, Plasmodium berghei N/13/1A/4/203 caused the death of mice, whereas Plasmodium chabaudi chabaudi AS was not lethal. Cur rent opinion is that nitric oxide (NO) and other reactive nitrogen intermed iates (RNI) are produced in several host organs during malaria to resist in fection or produce tissue damage. NO and RNI production in blood or plasma, brain, liver and spleen in MF1 mice was investigated during P. berghei and P. c. chabaudi infection, in order to help determine whether changes in NO production are beneficial or detrimental to the host in vivo. NO productio n was measured both directly and indirectly as nitrites and nitrates, to re present RNI. No changes in blood NO were detected in P. berghei infected mi ce, but increases were observed in brain, liver and spleen. In P. c. chabau di infected mice, rises in NO concentration were observed in blood and sple en, whereas a decline in liver NO was seen, but there were no changes in br ain. Liver contained the highest concentration of RNI, but increasing conce ntrations were seen in both plasma and spleen in both P. berghei and P. c. chabaudi infected mice. These results show that NO and RNI production alter s during murine malaria. The changes depend upon the tissue, the day of inf ection, the degree of parasitaemia, the strain of Plasmodia and the method of measuring NO biosynthesis. Lethal P. berghei induced NO production in th e mid and late stages of infection in mice when parasitaemia was high, wher eas in nonlethal P. c. chabaudi infection, NO production was increased in t he early and late stages when parasitaemia was low. These data are consiste nt with a role for NO in the protection of the MF1 mouse against Plasmodia. Failure to clear the parasite is associated with evidence of increased NO production in brain and liver, which may contribute to the pathology of mal aria, but this hypothesis requires confirmation from other experimental app roaches.