Filarial nematode secreted product ES-62 is an anti-inflammatory agent: Therapeutic potential of small molecule derivatives and ES-62 peptide mimetics
Filarial nematode secreted product ES-62 is an anti-inflammatory agent: Therapeutic potential of small molecule derivatives and ES-62 peptide mimetics
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DOI：
10.1111/j.1440-1681.2006.04400.x
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发表时间：
2006-05-01
影响因子：
2.9
通讯作者：
Harnett, MM
中科院分区：
文献类型：
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作者：
Harnett, W;Harnett, MM
1. “卫生假说”假设，最近西方过敏性或自身免疫性疾病（例如哮喘、I 型糖尿病）发病率的增加反映了儿童时期缺乏适当的传染源（例如寄生虫）启动免疫反应。2。与此相一致的是，人们很早就认识到，多种自身免疫性疾病，例如类风湿性关节炎 (RA)，一种辅助性 T (Th) 1 介导的自身免疫性疾病，其特征是促炎细胞因子（例如肿瘤坏死因子-a）的过量产生，在寄生虫负荷较高的地理区域中表现出发病率和严重程度降低，这表明环境因素可能会微妙地改变疾病进展。3。蠕虫感染似乎还可以抑制 Th2 偏向的炎症性疾病，例如哮喘，因为寄生虫负载和特应性之间似乎也存在负相关。这或许更令人惊讶，因为蠕虫经常诱导强烈的 Th2 型免疫反应，其特征是释放特定细胞因子，例如白细胞介素 (IL)-4、IL-5 和 IL-13.4。因此，这些发现表明，蠕虫与宿主的共同进化导致蠕虫能够调节炎症反应以促进寄生虫生存，也可能使宿主在没有感染的情况下产生自身免疫和过敏的倾向。5。这种免疫调节的机制尚不清楚，但似乎涉及寄生虫衍生分子的释放，这些分子允许蠕虫通过多种机制调节或逃避宿主免疫反应，包括细胞因子反应的倾斜和 T 调节细胞的诱导。6。在本综述中，我们讨论了一种丝虫线虫衍生的免疫调节分子（即 ES-62）的特性、其抗炎作用以及模拟其作用的小分子衍生物和肽的治疗潜力。
1. The 'hygiene hypothesis' postulates that the recent increased incidence of allergic or autoimmune diseases (e.g. asthma, type I diabetes) in the West reflects an absence of appropriate priming of the immune response by infectious agents, such as parasitic worms, during childhood.2. Consistent with this, it has long been recognized that several autoimmune disorders, such as rheumatoid arthritis (RA), a T helper (Th) 1-mediated autoimmune disease characterized by excess production of pro-inflammatory cytokines, such as tumour necrosis factor-a, exhibit reduced incidence and severity in geographical regions with high parasite load, suggesting that environmental factors may subtly alter disease progression.3. Infection with worms also appears to suppress Th2-biased inflammatory disorders, such as asthma, because there also appears to be an inverse correlation between parasite load and atopy. This is perhaps more surprising, given that helminths often induce strong Th2-type immune responses characterized by release of specific cytokines, such as interleukin (IL)-4, IL-5 and IL-13.4. Therefore, these findings suggest that the co-evolution of helminths with hosts, which has resulted in the ability of worms to modulate inflammatory responses in order to promote parasite survival, may also have generated a predisposition for the host to develop autoimmunity and allergy in the absence of infection.5. The mechanisms underlying such immunomodulation are not clear, but appear to involve the release of parasite-derived molecules that allow the worms to modulate or evade the host immune response by a number of mechanisms, including skewing of cytokine responses and the induction of T regulatory cells.6. In the present review we discuss the properties of one such filarial nematode-derived immunomodulatory molecule, namely ES-62, its anti-inflammatory action and the therapeutic potential of small molecule derivatives and peptides that mimic its action.