Dietert Rodney R
Department of Microbiology and Immunology, College of Veterinary Medicine, C5-135 VMC North Tower Road, Cornell University, Ithaca, NY 14853, USA.
Blood Cells Mol Dis. 2009 Mar-Apr;42(2):108-12. doi: 10.1016/j.bcmd.2008.10.005. Epub 2008 Nov 20.
The developing immune system is a sensitive target for environmentally-induced disruption producing postnatal immune dysfunction. Unique immune maturational events occur during critical windows of prenatal/perinatal development and environmentally-induced disruption of one-time events can have serious health consequences. Additionally, the specialized immunological conditions necessary to bring a semi-allogeneic fetus to term place restrictions on both the maternal and offspring immune systems. These features combine not only to increase the risk of early-life immune insult (ELII), which includes xenobiotically-induced developmental immunotoxicity (DIT), but also to influence the nature of DIT-associated diseases for the child. Exposure to certain toxicants as well as maternal infections and other pregnancy stressors is known to induce postnatal immune dysfunction. Because dysfunctional immune responses to childhood infections have been proposed to play a role in childhood leukemia, DIT is a potential risk factor for this disease. This review details the range of disease susceptibilities impacted by DIT and discusses the importance of effective DIT safety testing for drugs and chemicals as a preventative measure.
发育中的免疫系统是环境诱导破坏的敏感靶点,会导致出生后免疫功能障碍。独特的免疫成熟事件发生在产前/围产期发育的关键窗口期,环境诱导的一次性事件破坏可能会产生严重的健康后果。此外,使半同种异体胎儿足月出生所需的特殊免疫条件对母体和后代的免疫系统都有限制。这些特征不仅增加了早期生命免疫损伤(ELII)的风险,其中包括外源性物质诱导的发育免疫毒性(DIT),还影响儿童DIT相关疾病的性质。已知接触某些有毒物质以及母体感染和其他妊娠应激源会诱发出生后免疫功能障碍。由于对儿童感染的功能失调免疫反应被认为在儿童白血病中起作用,因此DIT是这种疾病的潜在风险因素。本综述详细介绍了受DIT影响的一系列疾病易感性,并讨论了作为预防措施对药物和化学品进行有效的DIT安全性测试的重要性。