Drug-induced immunotoxicity
Drug-induced immunotoxicity
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DOI：
10.1007/bf03189993
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发表时间：
1998-10-01
影响因子：
1.9
通讯作者：
Mansuy, D
中科院分区：
文献类型：
--
作者：
Dansette, PM;Bonierbale, E;Mansuy, D
免疫相关的药物反应是特异质毒性的最常见来源之一。许多器官可能是此类反应的靶点;然而，本综述主要集中在肝脏。药物性肝炎通常分为两类：急性肝炎，其中药物或代谢产物破坏细胞中的重要靶点;免疫过敏性肝炎，其中药物引发针对肝脏的不良免疫反应。他们的临床特征是：a）低频; B）剂量依赖性：c）典型的免疫系统表现，例如发热、嗜酸性粒细胞增多; d）治疗开始和疾病发作之间的延迟; e）再激发后的缩短的延迟;和f）患者血清中偶尔存在自身抗体。在氟烷、替尼酸、双肼屈嗪和抗惊厥药等药物引发的肝炎病例中发现了此类迹象。他们将被视为例子，以展示在确定负责该疾病的机制方面取得的最新进展。已经假设了以下机制：I）药物首先代谢成与产生它的酶结合的反应性代谢物; 2）这产生新抗原，一旦呈递给免疫系统，其可能触发免疫应答，其特征在于3）产生识别天然和/或修饰的蛋白质的抗体; 4）再激发导致新抗原产生增加，在这种情况下，抗体的存在可能诱导细胞溶解。毒性与新抗原的性质和数量有关，也与其他因素如个体免疫系统有关。应该努力更好地了解这种疾病的确切机制，从而确定有风险的药物;以及将其引入免疫系统所需的新抗原过程。在这方面，动物模型将是有用的。
Immune-related drug responses are one of the most common sources of idiosyncratic toxicity. A number of organs may be the target of such reactions; however, this review concentrates mostly on the liver. Drug-induced hepatitis is generally divided into two categories: acute hepatitis in which the drug or a metabolite destroys a vital target in the cell; immunoallergic hepatitis in which the drug triggers an adverse immune response directed against the liver. Their clinical features are: a) low frequency; b) dose independence: c) typical immune system manifestations such as fever, eosinophilia; d) delay between the initiation of treatment and onset of the disease; e) a shortened delay upon rechallenge; and f) occasional presence of autoantibodies in the serum of patients. Such signs have been found in cases of hepatitis triggered by drugs such as halothane, tienilic acid, dihydralazine and anticonvulsants. They will be taken as examples to demonstrate the recent progress made in determining the mechanisms responsible for the disease. The following mechanisms have been postulated: I) the drug is first metabolized into a reactive metabolite which binds to the enzyme that generated it; 2) this produces a neoantigen which, once presented to the immune system, might trigger an immune response characterized by 3) the production of antibodies recognizing both the native and/or the modified protein; 4) rechallenge leads to increased neoantigen production, a situation in which the presence of antibodies may induce cytolysis. Toxicity is related to the nature and amount of neoantigen and also to other factors such as the individual immune system. An effort should be made to better understand the precise mechanisms underlying this kind of disease and thereby identify the drugs at risk; and also the neoantigen processes necessary for their introduction into the immune system. An animal model would be useful in this regard.