Freebern Wendy Jo
Methods Mol Biol. 2010;598:109-17. doi: 10.1007/978-1-60761-401-2_8.
A foremost objective of preclinical immunotoxicity testing is to address whether or not a drug or environmental toxicant causes adverse effects on net immune health, expressly the host's ability to mount an appropriate immune response to clear infectious organisms. Given the complex interactions, diverse molecular signaling events, and redundancies of immunity that has itself been subdivided into interdependent arms, namely innate, adaptive, and humoral, the results of single immune parameter testing may not reflect the final outcome of a drug or toxicant's effect on net immune health. The most comprehensive experimental approach to ascertain this information is utilization of host resistance models. Herein, application of viral host resistance models in rodents and non-human primates is described. Although brief descriptions of numerous viral models are discussed including reovirus, Epstein-Barr virus, cytomegalovirus, and lymphocryptovirus, the most well-characterized viral host resistance model, rodent influenza, is emphasized.
临床前免疫毒性测试的一个首要目标是确定一种药物或环境毒物是否会对整体免疫健康产生不利影响，特别是宿主对清除感染性生物体产生适当免疫反应的能力。鉴于免疫本身已被细分为相互依存的几个分支，即先天免疫、适应性免疫和体液免疫，存在复杂的相互作用、多样的分子信号传导事件和冗余现象，单一免疫参数测试的结果可能无法反映药物或毒物对整体免疫健康的最终影响。确定此类信息的最全面实验方法是使用宿主抵抗力模型。本文描述了病毒宿主抵抗力模型在啮齿动物和非人类灵长类动物中的应用。虽然讨论了多种病毒模型的简要描述，包括呼肠孤病毒、爱泼斯坦-巴尔病毒、巨细胞病毒和淋巴细胞隐病毒，但重点强调了特征最明确的病毒宿主抵抗力模型——啮齿动物流感模型。
