Pallardy M, Kerdine S, Lebrec H
Immunotoxicology group, INSERM U461, Faculté de Pharmacie Paris-Sud, Chatenay-Malabry, France.
Toxicol Lett. 1998 Dec 28;102-103:257-60. doi: 10.1016/s0378-4274(98)00315-4.
Developing a battery of immune function assays to screen potential immunotoxic compounds has been a major issue these past years. Improving this approach is possible using new probes and parameters that are now available from recent knowledge on how the immune system is working (apoptosis, RT-PCR for cytokine mRNA expression). Immunotoxic outcome generally results in serious adverse effects, thus it seems appropriate to evaluate this risk early in drug development. This is especially true in the context of the emerging combinatorial chemistry techniques and high throughput screening in pharmacology resulting in probably numerous molecules to test in toxicology. In this case, screening for adverse effects (genotoxicity, hepatotoxicity, immunotoxicity) that may compromise definitely the development of a molecule should be a help in the decision process since more than one molecule with equivalent pharmacological properties may be available.
在过去几年中,开发一系列免疫功能检测方法以筛选潜在的免疫毒性化合物一直是一个主要问题。利用基于免疫系统工作原理的最新知识(细胞凋亡、细胞因子mRNA表达的逆转录聚合酶链反应)现有的新探针和参数,改进这种方法是可行的。免疫毒性结果通常会导致严重的不良反应,因此在药物开发早期评估这种风险似乎是合适的。在新兴的组合化学技术和药理学高通量筛选导致可能有大量分子需要进行毒理学测试的背景下,情况尤其如此。在这种情况下,筛选可能会绝对阻碍分子开发的不良反应(遗传毒性、肝毒性、免疫毒性),应该有助于决策过程,因为可能有不止一种具有等效药理特性的分子可供选择。