DeWitt Jamie C, Peden-Adams Margie M, Keil Deborah E, Dietert Rodney R
Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
Toxicol Pathol. 2012;40(2):230-6. doi: 10.1177/0192623311427709. Epub 2011 Nov 22.
Developmental immunotoxicity (DIT) occurs when exposure to environmental risk factors prior to adulthood, including chemical, biological, physical, or physiological factors, alters immune system development. DIT may elicit suppression, hyperactivation, or misregulation of immune responses and therefore may present clinically as decreased resistance to pathogens, allergic and autoimmune diseases, and inflammatory diseases. When evaluating DIT in an animal model, specific endpoints are assessed, which can reveal the potential for a risk factor to alter immune system development. However, linking DIT evaluation in an animal model with clinical realities observed in human populations requires that DIT testing regimens evaluate critical windows in immune system development. In addition, pathways leading to DIT may not be apparent without the stressors that induce aberrant and detectable responses. This review contains brief descriptions of recently published work that addresses disease patterns associated with DIT and solutions for altering such patterns of disease. We also comment on gaps between DIT testing in animal models and the clinical manifestation of immune-based diseases in children that can be filled by a better understanding of critical windows in immune system development and DIT testing that includes multiple functional assays.
发育性免疫毒性（DIT）是指在成年前接触环境风险因素（包括化学、生物、物理或生理因素）时，免疫系统发育发生改变。DIT可能引发免疫反应的抑制、过度激活或调节异常，因此在临床上可能表现为对病原体的抵抗力下降、过敏性和自身免疫性疾病以及炎症性疾病。在动物模型中评估DIT时，会评估特定的终点指标，这些指标可以揭示风险因素改变免疫系统发育的可能性。然而，要将动物模型中的DIT评估与人类群体中观察到的临床实际情况联系起来，就要求DIT测试方案评估免疫系统发育的关键窗口期。此外，如果没有诱导异常且可检测反应的应激源，导致DIT的途径可能并不明显。本综述简要介绍了最近发表的有关与DIT相关的疾病模式以及改变此类疾病模式的解决方案的研究工作。我们还评论了动物模型中的DIT测试与儿童免疫性疾病临床表现之间的差距，通过更好地理解免疫系统发育的关键窗口期以及包括多种功能测定的DIT测试可以填补这些差距。
