Internal Medicine B, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Ramat Gan, 52621, Israel.
Clin Rev Allergy Immunol. 2013 Oct;45(2):211-6. doi: 10.1007/s12016-012-8352-9.
The incidence of autoimmune diseases is increasing in Western countries, possibly due to the improved sanitary conditions and reduced exposure to infections in childhood (the hygiene hypothesis). There is an ongoing debate whether infection prevents or precipitates autoimmune diseases. Various helminths species used in several animal models were shown to limit inflammatory activity in a variety of diseases including inflammatory bowel disease, multiple sclerosis, type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. At present the scientific data is based mostly on experimental animal models; however, there is an increasing body of evidence in a number of clinical trials being conducted. Herein we review several clinical trials evaluating the anti-inflammatory effects of helminths and assessing their association with different autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, and autoimmune liver diseases. We also describe the common pathways by which helminths induce immune modulation and the key changes observed in the host immune system following exposure to helminths. These common pathways include the inhibition of IFN-γ and IL-17 production, promotion of IL-4, IL-10 and TGF-β release, induction of CD4(+) T cell FoxP3(+) expression, and generation of regulatory macrophages, dendritic cells, and B cells. Helminths products are becoming significant candidates for anti-inflammatory agents in this context. However, further research is needed for synthetic analogues of helminths' potent products that mimic the parasite-mediated immunomodulation effect.
自身免疫性疾病在西方国家的发病率正在上升，这可能是由于儿童时期卫生条件改善和感染暴露减少（卫生假说）所致。目前仍在争论感染是预防还是引发自身免疫性疾病。在几种动物模型中使用的各种寄生虫物种被证明可以限制多种疾病的炎症活动，包括炎症性肠病、多发性硬化症、1 型糖尿病、类风湿关节炎和系统性红斑狼疮。目前，科学数据主要基于实验动物模型；然而，正在进行的许多临床试验提供了越来越多的证据。在此，我们回顾了几项评估寄生虫抗炎作用及其与几种自身免疫性疾病（包括炎症性肠病、多发性硬化症和自身免疫性肝病）关联的临床试验。我们还描述了寄生虫诱导免疫调节的常见途径以及宿主免疫系统在接触寄生虫后观察到的关键变化。这些常见途径包括抑制 IFN-γ 和 IL-17 的产生、促进 IL-4、IL-10 和 TGF-β 的释放、诱导 CD4(+)T 细胞 FoxP3(+)表达以及产生调节性巨噬细胞、树突状细胞和 B 细胞。在这种情况下，寄生虫产物正成为抗炎药物的重要候选物。然而，需要进一步研究寄生虫有效产物的合成类似物，以模拟寄生虫介导的免疫调节作用。
