Muniz-Junqueira Maria Imaculada
Laboratory of Cellular Immunology, Faculty of Medicine, University of Brasilia, 70.910-900, Brasília, DF, Brazil.
Curr Clin Pharmacol. 2007 Jan;2(1):59-73. doi: 10.2174/157488407779422285.
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.
疟疾是一个重要的公共卫生问题。据估计，每年有3.5亿至5亿临床病例发生，每年导致110万至130万人死亡。免疫系统的过度激活在该疾病的发病机制中起重要作用。感染疟原虫个体的免疫系统细胞不仅会产生大量具有抗寄生虫作用的细胞因子，还会参与疟疾严重并发症的发病过程。恶性疟原虫感染的一个主要特征是被寄生的红细胞在主要器官的小血管内滞留。这涉及被寄生红细胞的抗原与内皮细胞表面表达的宿主受体之间的分子相互作用。促炎细胞因子和一氧化氮的产生增加，随后内皮细胞黏附分子上调，影响脑部病变的进展。已经评估了能够调节对抗疟药物免疫反应的药物的联合使用情况。为此尝试了肿瘤坏死因子抗体、己酮可可碱和沙利度胺，取得了不同程度的成功。本综述对该主题进行了批判性评估，并提出了利用与抗寄生虫治疗相关的免疫调节药物来降低疟疾病死率的方法。
