UP-REGULATION OF REACTIVE OXYGEN AND NITROGEN INTERMEDIATES IN PLASMODIUM-BERGHEI-INFECTED MICE AFTER RESCUE THERAPY WITH CHLOROQUINE OR ARTEMETHER

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghe i infected mice were treated with artemether, chloroquine or clindamyc in 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 mala ria showed a slight decrease in their capacity to produce reactive oxy gen intermediates (ROI) when compared with naive mice. After artemethe r or chloroquine treatment, the ROI production was significantly enhan ced. The interferon-gamma induced production of reactive nitrogen inte rmediates (RNI) was slightly elevated in mice with cerebral malaria, b ut markedly elevated in artemether or chloroquine treated mice when co mpared with naive mice. Moreover, high levels of inducible nitric oxid e synthase gene expression could be detected by in-situ hybridization in spleen sections of mice which had been treated with artemether or c hloroquine. These findings suggest that increased production of ROI an d RNI after chemotherapy may play a protective role for the host durin g malaria.