Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether.

Abstract

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. Artemether and chloroquine were highly efficient. Functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen intermediates (ROI) when compared with naive mice. After artemether or chloroquine treatment, the ROI production was significantly enhanced. The interferon-gamma induced production of reactive nitrogen intermediates (RNI) was slightly elevated in mice with cerebral malaria, but markedly elevated in artemether or chloroquine treated mice when compared with naive mice. Moreover, high levels of inducible nitric oxide synthase gene expression could be detected by in-situ hybridization in spleen sections of mice which had been treated with artemether or chloroquine. These findings suggest that increased production of ROI and RNI after chemotherapy may play a protective role for the host during malaria.