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Malaria Research and Treatment
Volume 2012, Article ID 679090, 12 pages
http://dx.doi.org/10.1155/2012/679090
Research Article

Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF- B Translocation in a Mechanism Independent of Plasmodium Killing

1Laboratório de Farmacologia Aplicada, Departamento de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
2Laboratório de Educação Profissional em Técnicas Laboratoriais em Saúde, Escola Politécnica de Saúde Joaquim Venâncio, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
3Drugs for Neglected Diseases Initiative, Geneva, Switzerland

Received 30 May 2012; Revised 16 August 2012; Accepted 30 August 2012

Academic Editor: Mats Wahlgren

Copyright © 2012 Mariana C. Souza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities. Few studies have addressed the effect of artesunate in the murine malaria model or its effect on host immune response during malaria infection. Herein, we study the effect of artesunate treatment and describe an auxiliary mechanism of artesunate in modulating the inflammatory response during experimental malaria infection in mice. Treatment with artesunate did not reduce significantly the parasitemia within 12 h, however, reduced BBB breakdown and TNF-α mRNA expression in the brain tissue of artesunate-treated mice. Conversely, mefloquine treatment was not able to alter clinical features. Notably, artesunate pretreatment failed to modulate the expression of LFA-1 in splenocytes stimulated with parasitized red blood cells (pRBCs) in vitro; however, it abrogated the expression of ICAM-1 in pRBC-stimulated endothelial cells. Accordingly, a cytoadherence in vitro assay demonstrated that pRBCs did not adhere to artesunate-treated vascular endothelial cells. In addition, NF-κB nuclear translocation in endothelial cells stimulated with pRBCs was impaired by artesunate treatment. Our results suggest that artesunate is able to exert a protective effect against the P. berghei-induced inflammatory response by inhibiting NF-κB nuclear translocation and the subsequent expression of ICAM-1.