药物超敏反应安全评价体外替代方法的研究进展

超敏反应是药物的严重不良反应之一,严重时可危及患者生命。目前超敏反应(Ⅰ,Ⅳ型)临床前评价方法多为整体动物实验方法,基于动物福利和3R原则的考虑,以及体外替代方法的迅速发展,目前已建立了数种药物致敏性评价的体外替代方法,包括根据肥大细胞和嗜碱性粒细胞在Ⅰ型超敏反应中发挥的关键作用,用实验室易获得的肥大细胞和嗜碱性粒细胞系如RBL-2H3和KU812研究药物的Ⅰ型超敏反应,另外鉴于树突状细胞在Ⅳ型超敏反应中抗原呈递作用,用THP-1细胞构建的h-CLAT试验体系和LC-SA试验体系在皮肤致敏性的评价方面都显示出较好的发展前景。本文综合近年的国内外文献,对超敏反应的体外替代方法进行了综合论述和评估。

In vitro alternatives to safety assessment of drug-induced hypersensitivity reactions

As one of the most frequent adverse effects induced by drugs,hypersensitivity reactions may result in severe morbidity and fatalities.It’s critical to evaluate the allergy potential of new drugs and other chemicals,and usually animal experiments are used in the preclinical assessment.Considering animal welfare and 3R principles,in vitro alternatives to animal experiments have been developed to predict the hypersensitivity potential by simulating the physiological and pathological mechanism of hypersensitivity.The available cell lines RBL-2H3 and KU812 are used to study typeⅠhypersensitivity because mast cells and basophils play a critical role in the process of type Ⅰhypersensitivity.Similarly,because dendritic cells are important APC,h-CLAT(human cell line activation test) and LCSA(loose-fit coculture-based sensitization assay) are established to evaluate type Ⅳ hypersensitivity.Throuth reviewing the literature in recent years,this article makes a comprehensive introduction and evaluation of the alternatives to safety assessment of drug-induced hypersensitivity reactions.