Immunomodulatory Therapy Associated to Anti-Parasite Drugs as a Way to Prevent Severe Forms of Malaria

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Abstract:

Malaria is an important problem of public health. It is estimated that 350 to 500 million clinical cases occur annually, which cause 1.1 and 1.3 million deaths every year. The excessive activation of the immune system plays an important role in the pathogenesis of the disease. The cells of the immune system of Plasmodium-infected individuals not only produce large amounts of cytokines, which have anti-parasite effects, but also participate in the pathogenesis of the severe complications of malaria. A central feature of P. falciparum infection is the sequestration of parasitized erythrocytes within the small vessels of major organs. This involves molecular interactions between antigens of parasitized erythrocytes and host receptors, expressed on the surface of endothelial cells. The increased production of pro-inflammatory cytokines and nitric oxide, followed by the up regulation of endothelial cell adhesion molecules, influences the progression of cerebral lesions. The association of drugs capable of modulating the immune response to anti plasmodial drugs has been evaluated. Antibodies to tumor necrosis factor, pentoxifylline, and thalidomide have been tried for this purpose with variable success. This review submitted this subject to a critical assessment and suggests ways to take advantage of immunomodulatory drugs, associated to anti parasite therapy, to reduce the morbimortality of malaria.





Keywords: Malaria; Plasmodium falciparum; TNF; cerebral malaria; cytokines; immunomodulation; immunopathogenesis; pentoxifylline; thalidomide; tumor necrosis factor

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/157488407779422285

Affiliations: Laboratory of Cellular Immunology,Faculty of Medicine, University of Brasilia, 70.910-900, Brasília,DF, Brazil.

Publication date: January 1, 2007

More about this publication?
  • Current Clinical Pharmacology publishes frontier reviews on all the latest advances in clinical pharmacology. The journal's aim is to publish the highest quality review articles in the field. Topics covered include: pharmacokinetics; therapeutic trials; adverse drug reactions; drug interactions; drug metabolism; pharmacoepidemiology; and drug development. The journal is essential reading for all researchers in clinical pharmacology.
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