The role of cytokines in the mechanism of adverse drug reactions.
The role of cytokines in the mechanism of adverse drug reactions.
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DOI：
10.1007/978-3-642-00663-0_8
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发表时间：
2010-01-01
影响因子：
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通讯作者：
Pohl, Lance R
中科院分区：
文献类型：
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作者：
Masson, Mary Jane;Collins, Lindsay A;Pohl, Lance R
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，因为它们能够调节先天性和适应性免疫系统。由于细胞因子的多能性，这种作用是高度复杂的，这使得相同的细胞因子能够根据所涉及的靶器官发挥多种作用。因此，根据靶器官组织了ADR中细胞因子参与的讨论;特别是靶向皮肤和肝脏的ADR，以及靶向多个器官的ADR，如药物诱导的自身免疫和输注相关反应。除了讨论细胞因子促进ADR的发生、传播和消退的机制外，我们还讨论了目前进行此类机制研究的方法的有用性和局限性。虽然动物模型似乎最有希望揭示额外的机制，但该领域受到缺乏良好动物模型的困扰，因此，通常使用信息量较少的体外研究来研究细胞因子参与ADR的机制。最近形成的药物性肝损伤网络，其目标是从药物性肝损伤患者中收集数千份样本，通过进行大规模细胞因子多态性研究，具有推动该领域知识发展的巨大潜力。总之，我们讨论了如何在这一领域的进一步发展可能是显着的好处，患者在预防，预测和治疗药物不良反应。
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.