Methodologies for developmental immunotoxicity (DIT) testing
Methodologies for developmental immunotoxicity (DIT) testing
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DOI：
10.1016/j.ymeth.2006.06.018
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发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Holsapple, Michael P.
中科院分区：
文献类型：
--
作者：
Dietert, Rodney R.;Holsapple, Michael P.
发育性免疫毒性作为影响日后生活疾病风险的重要因素已得到越来越多的认识。根据目前收集到的关于不同化学物质和药物的数据，发育中的免疫系统可能比成人的免疫系统对外源诱导的损伤更为敏感。出生前后的免疫系统与成熟成人的免疫系统存在明显差异，免疫毒性变化的性质也存在年龄差异。免疫抑制并不是唯一的问题。免疫毒性变化增加过敏或自身免疫反应的风险也应考虑在内。因此，我们不应该认为，成人暴露评估验证的免疫毒性分析本质上是最具预测性的发育免疫毒理学（DIT）评估。许多基于成人的方案仅用于检测免疫抑制，而DIT的关注点包括免疫平衡的变化。因此，检查最近围产期免疫毒性研究中使用的各种免疫终点，将其与常规成人免疫毒性评估方案进行比较，并考虑可用于有效DIT测试的选项是有用的。近年来发表的几种化学品和药物的结果表明，功能试验是围产期免疫毒性检测的首要任务，至少两种功能试验（如多同型T依赖性抗体反应（tdar））和细胞介导的免疫反应试验（如延迟型超敏试验和/或T细胞或NK细胞毒性试验）的组合应与免疫细胞群和组织病理学分析相结合。细胞因子生产测量提供了突出的前景，并可能最终能够取代其他更费力的程序。然而，多细胞因子分析需要在最佳分析来源和方案方面标准化。(c) 2006爱思唯尔公司版权所有。
Developmental immumotoxicity has gained increasing recognition as a significant factor influencing the risk of later life disease. Based on the data collected thus far on different chemicals and drugs, the developing immune system can be significantly more sensitive than the adult immune system to xenobiotic-induced insult. There are distinct differences between the immune system surrounding birth and that in the mature adult as well as differences in the nature of immunotoxic changes based on age. Immunosuppresssion is not the only concern. Immunotoxic changes that increase the risk for allergic or autoimmune responses should also be considered. Therefore, one should not assume that immunotoxicity assays validated for adult exposure assessment are inherently the most predictive for developmental immunotoxicology (DIT) evaluation. Many of those adult-based protocols were developed solely to detect immunosuppression, whereas DIT concerns include shifts in immune balance. For this reason, it is useful to examine the various immune endpoints that have been employed in recent perinatal immunotoxicity studies, compare those against routine adult immunotoxicity evaluation protocols, and consider the options that are available for effective DIT testing. The results published on several chemicals and drugs in recent years suggest that functional tests are a front-line priority for perinatal immunotoxicity detection and that a combination of at least two functional tests (such as a multi-isotype T-dependent antibody response (TDARs), and a cell-mediated immune response assay such as the delayed-type hypersensitivity assay and/or T cell or NK cytotoxicity assays) should be paired with immune cell populations and histopathological analysis. Cytokine production measurements offer outstanding promise and may eventually be able to be substituted for other more laborious procedures. However, multi-cytokine analysis needs to be standardized in terms of optimum source for analysis and protocol. (c) 2006 Elsevier Inc. All rights reserved.