Johns Hopkins University, Department of Anesthesiology and Critical Care Medicine, 600 North Wolfe Street, Baltimore 21287, USA.
Expert Opin Drug Metab Toxicol. 2010 May;6(5):519-31. doi: 10.1517/17425251003601979.
Idiosyncratic drug reactions resulting in drug-induced liver injury (DILI) account for approximately 13% of acute liver failure cases in the US. Idiosyncratic drug reactions are the third most common cause of liver transplantation, exceeded only by acetaminophen and indeterminate causes. Clinical evidence suggests that idiosyncratic DILI is triggered by drug hapten-altered self proteins resulting in hepatocellular injury. An example of this type of DILI is hepatitis that develops in susceptible individuals following administration of halogenated volatile anesthetics, dihydralazine, carbamazepine or diclofenac.
In this review, we describe research in animal models that supports a critical role for suppressive and pro-inflammatory roles for IL-4 in the pathogenesis of immune-mediated DILI.
The reader will gain insights into the roles of IL-4 in the development of experimental DILI. The reader will gain tools to assist in the translation of these findings to those in patients with immune-mediated DILI, as well as other inflammatory diseases of the liver. The reader will then be made aware of gaps in knowledge in the pathogenesis of DILI where research could result in significant advances in the care of these complicated patients.
In experimental immune-mediated DILI, IL-4 suppresses regulatory responses to CYP2E1 autoantigens but induces pro-inflammatory responses to drug haptens.
导致药物性肝损伤 (DILI) 的药物特应性反应约占美国急性肝衰竭病例的 13%。药物特应性反应是肝移植的第三大常见原因，仅次于对乙酰氨基酚和原因不明。临床证据表明，药物特应性 DILI 是由药物半抗原改变的自身蛋白触发的，导致肝细胞损伤。这种类型的 DILI 的一个例子是，在易感个体中，给予卤化挥发性麻醉剂、二氢拉嗪、卡马西平和双氯芬酸后，会发生肝炎。
在这篇综述中，我们描述了支持 IL-4 在免疫介导的 DILI 发病机制中具有抑制和促炎作用的动物模型研究。
读者将深入了解 IL-4 在实验性 DILI 发展中的作用。读者将获得有助于将这些发现转化为免疫介导的 DILI 患者以及其他肝脏炎症性疾病患者的工具。然后，读者将意识到 DILI 发病机制中的知识空白，如果进行研究，这些患者的护理可能会取得重大进展。
在实验性免疫介导的 DILI 中，IL-4 抑制对 CYP2E1 自身抗原的调节反应，但诱导对药物半抗原的促炎反应。
