Masson Mary Jane, Collins Lindsay A, Pohl Lance R
Laboratory of Molecular and Cellular Toxicology, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Handb Exp Pharmacol. 2010(196):195-231. doi: 10.1007/978-3-642-00663-0_8.
Cytokines are thought to play a role in acute and/or immune-mediated adverse drug reactions (ADRs) due to their ability to regulate the innate and adaptive immune systems. This role is highly complex owing to the pluripotent nature of cytokines, which enables the same cytokine to play multiple roles depending on target organ(s) involved. As a result, the discussion of cytokine involvement in ADRs is organized according to target organ(s); specifically, ADRs targeting skin and liver, as well as ADRs targeting multiple organs, such as drug-induced autoimmunity and infusion-related reactions. In addition to discussing the mechanism(s) by which cytokines contribute to the initiation, propagation, and resolution of ADRs, we also discuss the usefulness and limitations of current methodologies available to conduct such mechanistic studies. While animal models appear to hold the most promise for uncovering additional mechanisms, this field is plagued by a lack of good animal models and, as a result, the mechanism of cytokine involvement in ADRs is often studied using less informative in vitro studies. The recent formation of the Drug-Induced Liver Injury Network, whose goal is collect thousands of samples from drug-induced liver injury patients, has enormous potential to advance knowledge in this field, by enabling large-scale cytokine polymorphism studies. In conclusion, we discuss how further advances in this field could be of significant benefit to patients in terms of preventing, predicting, and treating ADRs.
细胞因子被认为在急性和/或免疫介导的药物不良反应（ADR）中发挥作用，因为它们具有调节先天性和适应性免疫系统的能力。由于细胞因子具有多能性，即同一细胞因子可根据所涉及的靶器官发挥多种作用，所以其作用非常复杂。因此，关于细胞因子参与药物不良反应的讨论是根据靶器官来组织的；具体来说，是针对皮肤和肝脏的药物不良反应，以及针对多个器官的药物不良反应，如药物诱导的自身免疫和输液相关反应。除了讨论细胞因子促成药物不良反应的起始、传播和消退的机制外，我们还讨论了进行此类机制研究的现有方法的实用性和局限性。虽然动物模型似乎最有希望揭示更多机制，但该领域因缺乏良好的动物模型而受到困扰，因此，细胞因子参与药物不良反应的机制通常使用信息较少的体外研究来进行研究。药物性肝损伤网络的近期形成，其目标是从药物性肝损伤患者中收集数千份样本，通过开展大规模细胞因子多态性研究，在推进该领域知识方面具有巨大潜力。总之，我们讨论了该领域的进一步进展如何在预防、预测和治疗药物不良反应方面对患者带来显著益处。
