Johns Hopkins University, Bloomberg School of Public Health, CAAT, Baltimore, USA and University of Konstanz, CAAT-Europe, Germany.
ALTEX. 2013;30(4):411-26. doi: 10.14573/altex.2013.4.411.
Over the last two decades, little has changed in the practice of immunotoxicity testing for regulatory purposes, especially for immunosuppression, and autoimmunity is still a challenge. Current guidelines still rely on animal tests, which include some immune endpoints in repeated dose tests and trigger dedicated tests only when certain alerts indicate a problem. At the same time, however, a wealth of in vitro approaches has been developed, but few have been adopted for routine testing. The extent to which immunotoxicity of chemicals represents a health problem for the human population at low levels of exposure is unclear: it appears that responses of healthy individuals to immunological challenges differ widely and most immunomodulators have few adverse effects except when they coincide with an infectious or malignant challenge or when early in life exposure is expected, in which cases the odds of progressing into infection, autoimmune diseases, or cancer can be changed. The enormous overcapacity of immune defense, the presence of compensatory mechanisms, and their fast restoration each contribute to limiting health threats for the individual, though on a population base also minor immunomodulation may result in increased morbidity. In vitro alternative approaches may allow screening for problematic substances and prioritize them for in vivo testing. New approaches are emerging from mapping pathways of immunotoxicity. Increasingly, the contribution of inflammatory and infectious components to the adverse outcome pathways of chemicals is recognized for various hazards, urging inclusion of tests for proinflammatory and immunomodulatory properties of chemicals into integrated testing strategies.
在过去的二十年中，免疫毒性测试的实践几乎没有变化，特别是在免疫抑制和自身免疫方面仍然是一个挑战。当前的指南仍然依赖于动物测试，这些测试包括重复剂量测试中的一些免疫终点，并仅在某些警报表明存在问题时触发专门的测试。然而，与此同时，已经开发出了大量的体外方法，但很少有方法被用于常规测试。在低暴露水平下，化学物质的免疫毒性对人类健康构成多大的问题尚不清楚：似乎健康个体对免疫挑战的反应差异很大，大多数免疫调节剂除了在感染或恶性挑战时或在预期生命早期暴露时外，几乎没有不良影响，在这种情况下，感染、自身免疫性疾病或癌症进展的几率可能会发生变化。免疫防御的巨大过剩能力、代偿机制的存在以及它们的快速恢复都有助于限制个体的健康威胁，但在人群基础上，轻微的免疫调节也可能导致发病率增加。体外替代方法可以筛选出有问题的物质，并将其优先用于体内测试。新的方法正在从免疫毒性途径的映射中出现。对于各种危害，越来越多的人认识到炎症和感染成分对化学物质不良后果途径的贡献，这促使将化学物质的促炎和免疫调节特性测试纳入综合测试策略中。
