Journal
INTERNATIONAL JOURNAL FOR PARASITOLOGY
Volume 39, Issue 3, Pages 363-370Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ijpara.2008.10.005
Keywords
Cerebral malaria; Indoleamine 2,3-dioxygenase; Kynurenic acid; Kynurenine pathway; Picolinic acid; Quinolinic acid; Tryptophan metabolism
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Funding
- National Health and Medical Research Council of Australia
- Australian Research Council
- Australian Postgraduate Award
- Faculty of Medicine, University of Sydney
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Cerebral malaria (CM) can be a fatal manifestation of Plasmodium falciparum infection. In this study, two different approaches were used to examine the role of indoleamine 2,3-dioxygenase-1 (IDO-1) and its metabolites in the development of murine CM. Mice genetically deficient in IDO-1 were not protected against CM, but partial protection was observed in C57BL/6 mice treated with Ro 61-8048, an inhibitor of kynurenine-3-hydroxylase. This protection was associated with suppressed levels of picolinic acid (PA) within the brain, but not with changes in the levels of kynurenic acid (KA) or quinolinic acid (QA). These data suggest that although IDO-1 is not directly involved in the pathogenesis of CM in C57BL/6 mice, the production of the kynurenine pathway metabolite PA may contribute to the development of murine CM. (c) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
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