A missing link in the hygiene hypothesis?
A missing link in the hygiene hypothesis?
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DOI：
10.1007/s00125-002-0801-1
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发表时间：
2002-04-01
期刊：
影响因子：
8.2
通讯作者：
Gale, EAM
中科院分区：
文献类型：
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作者：
Gale, EAM
儿童I型(胰岛素依赖型)糖尿病的发病率与儿童哮喘的发病率同步上升，卫生学假说认为这是由于早期并发感染对免疫系统的刺激减少所致。如果是这样的话，这种保护作用可能是由调节性T淋巴细胞介导的。共同进化的伙伴可能对这种形式的反应的发展做出了贡献，寄生虫和肠道的本土生物群是看似合理的候选者。蠕虫通过诱导调节性T细胞和分泌II-10来抑制特应性疾病的发展，蛔虫则抑制非肥胖糖尿病(NOD)小鼠的糖尿病发展。西方世界最成功的人类蠕虫是蛔虫，欧洲和北美大约50%的幼儿可能在20世纪中叶左右受到过感染。蛔虫是良性的，通常没有症状，可能具有免疫调节特性，防止发生免疫介导的疾病，包括糖尿病和哮喘。他们对生活条件改善的反应能力下降可能解释了儿童特应性疾病和糖尿病的一些流行病学特征。建议的作用将是一种免疫调节而不是诱导疾病，可能通过与其他影响粘膜免疫系统发育的相互作用来调节。这一假设可以通过发展血清学标志物或皮肤试验在病例对照研究中得到验证。如果得到证实，对潜在机制的识别可能会为新形式的免疫干预开辟道路。
The incidence of childhood Type I (insulin-dependent) diabetes mellitus has risen in parallel with that of childhood asthma, and the hygiene hypothesis proposes that this is due to reduced stimulation of the immune system by early intercurrent infection. If so, this protective effect is probably mediated by regulatory T lymphocytes. Co-evolutionary partners might have contributed to the development of this form of response, and parasites and the indigenous biota of the gut are plausible candidates. Helminths inhibit the development of atopic disease via induction of regulatory T cells and secretion of II-10, and pinworms inhibit diabetes development in the non-obese diabetic (NOD) mouse. The most successful human helminth of the western world is the pinworm Enterobius vermicularis, and some 50% of young children in Europe and North America may have been infested around the middle of the twentieth century. Pinworms are benign, usually asymptomatic, and may have immunomodulatory properties that protect against the development of immune-mediated disorders including diabetes and asthma. Their decline in response to improved living conditions might explain a number of features of the epidemiology of childhood atopy and diabetes. The proposed role would be one of immunomodulation rather than disease induction, possibly mediated by interaction with other influences upon the development of the mucosal immune system. This hypothesis could be tested in case-control studies by the development of serological markers or skin testing. If confirmed, identification of the underlying mechanisms could open the way to new forms of immune intervention.