Burleson Stefanie C M, Freebern Wendy Jo, Burleson Florence G, Burleson Gary R, Johnson Victor J, Luebke Robert W
Burleson Research Technologies, Inc. (BRT), Morrisville, NC, USA.
Bristol-Myers Squibb Company, Immunotoxicology, New Brunswick, NJ, USA.
Methods Mol Biol. 2018;1803:117-145. doi: 10.1007/978-1-4939-8549-4_9.
The goal of immunotoxicity testing is to obtain data useful for immunotoxicity safety assessment. Guidance in the performance of immunotoxicity safety evaluations is provided in documents from the US EPA for chemicals and the ICH S8 document for pharmaceuticals. The ICH S8 document outlines a tiered approach that includes (1) standard toxicity studies with associated hematology, immune system organ weights, and histopathology data; (2) functional assays, such as cytotoxic T lymphocyte (CTL) assays, natural killer (NK) cell assays, respiratory burst, phagocytosis, and T-cell-dependent antibody response (TDAR) assays; and (3) host resistance assays. Host resistance assays are considered the gold standard in immunotoxicity testing and provide a critical overview of the extent to which innate, adaptive, and homeostatic regulatory immune functions are integrated to protect the host. Both comprehensive and targeted host resistance assays are available, each with distinct advantages. This chapter serves to provide a general overview of the various assays that may be used, as well as a summary of procedures.
免疫毒性测试的目的是获取对免疫毒性安全性评估有用的数据。美国环境保护局（US EPA）关于化学品的文件以及国际人用药品注册技术协调会（ICH）S8文件为免疫毒性安全性评估的实施提供了指导。ICH S8文件概述了一种分层方法，包括：（1）伴有相关血液学、免疫系统器官重量和组织病理学数据的标准毒性研究；（2）功能测定，如细胞毒性T淋巴细胞（CTL）测定、自然杀伤（NK）细胞测定、呼吸爆发、吞噬作用以及T细胞依赖性抗体反应（TDAR）测定；以及（3）宿主抵抗力测定。宿主抵抗力测定被视为免疫毒性测试的金标准，它能对固有免疫、适应性免疫和稳态调节免疫功能整合起来保护宿主的程度提供关键概述。全面的和有针对性的宿主抵抗力测定方法都有，每种方法都有其独特优势。本章旨在对可能使用的各种测定方法进行总体概述，并总结相关程序。
