Imai Shinjiro, Fujita Koichiro
Section of Environmental Parasitology, Department of International Health Development, Division of Public Health, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8519, Japan.
Curr Top Med Chem. 2004;4(5):539-52. doi: 10.2174/1568026043451285.
Parasite molecules offer unique advantages for the treatment of immunologicical disorders, and several candidate molecules have been shown to be effective. In our studies, it was shown that a factor inducing immunoglobulin E from filarial nematode parasites was suppressive in animal models of immunological disorders such as allergy and insulin dependent diabetes mellitus (IDDM). The Th1/Th2 paradigm of CD4+ T helper cell subsets can provide the basis for the development of new types of drugs and of novel strategies for the treatment of allergic and autoimmune disorders by parasite molecules. In our experimental system, parasite molecules from a filarial nematode parasite led to the down-regulation of the allergic reaction in animal models. In the majority of hosts, infection with helminths is associated with markedly reduced cellular immune reactions and polarization of T cell responses to Th2 and Th3 types. Some studies have suggested that the stimulation of host immunoregulatory networks with parasite molecules leading to the synthesis of anti-inflammatory cytokines (interleukin10, transforming growth factor-beta (TGF-beta and others) can provide new therapy for immunological disorders. It is known that parasites produce some types of molecule that mimic host molecules such as CD40 ligand, TGF-beta and macrophage migration inhibitory factor. These molecules are also candidates for medicinal agents. This review describes many of the latest possibilities in this field and shows how they can be best put to use for the development of medicinal agents, molecular target identification, and for prioritization.
寄生虫分子为免疫紊乱的治疗提供了独特优势，并且已证明几种候选分子是有效的。在我们的研究中，已表明来自丝虫线虫寄生虫的一种诱导免疫球蛋白E的因子在诸如过敏和胰岛素依赖型糖尿病（IDDM）等免疫紊乱的动物模型中具有抑制作用。CD4 + T辅助细胞亚群的Th1/Th2模式可为开发新型药物以及利用寄生虫分子治疗过敏和自身免疫性疾病的新策略提供基础。在我们的实验系统中，来自丝虫线虫寄生虫的寄生虫分子导致动物模型中过敏反应的下调。在大多数宿主中，蠕虫感染与细胞免疫反应明显降低以及T细胞反应向Th2和Th3类型极化有关。一些研究表明，用寄生虫分子刺激宿主免疫调节网络导致合成抗炎细胞因子（白细胞介素10、转化生长因子-β（TGF-β等）可为免疫紊乱提供新的治疗方法。已知寄生虫产生一些模仿宿主分子的分子类型，如CD40配体、TGF-β和巨噬细胞迁移抑制因子。这些分子也是药物候选物。本综述描述了该领域的许多最新可能性，并展示了如何将它们最佳地用于药物开发、分子靶点鉴定和优先级确定。
