Descotes J, Patriarca C, Vial T, Verdier F
Department of Pharmacology, Medical Toxicology and Environmental Medicine, INSERM U80, Faculty of Medicine Lyon-RTH Laennec, France.
Toxicology. 1997 Apr 11;119(1):45-9. doi: 10.1016/s0300-483x(96)03595-0.
The popliteal lymph node (PLN) assay is based on the assumption that a mechanism similar to a graft-versus-host (GvH) reaction is involved in 'GvH-like' drug-induced side-effects, including generalized lymphadenopathy, serum sickness-like disease, scleroderma-like reaction and the lupus syndrome. An increased PLN weight 7-10 days after injection of the test article into the footpad is generally held as a positive response. Most, if not all compounds reported to induce pseudo-GvH side-effects in man (namely positive model compounds) have been shown to induce positive PLN responses in mice and/or rats. Reproducible results have been obtained in several laboratories, in some instances blindly. However, positive responses have also been obtained with the negative model compounds acetone and imipramine. Flow cytometry analysis and conventional histology failed to help differentiate between a true GvH response and a primary irritative effect. In order to confirm the potential value of the PLN assay to predict the risk for drug-induced GvH-like reactions, mechanistic studies are urgently needed.
腘淋巴结(PLN)试验基于这样一种假设,即类似于移植物抗宿主(GvH)反应的机制参与了“类GvH”药物诱导的副作用,包括全身性淋巴结病、血清病样疾病、硬皮病样反应和狼疮综合征。将受试物注射到足垫7至10天后,PLN重量增加通常被视为阳性反应。据报道,大多数(如果不是全部的话)在人体中诱导假性GvH副作用的化合物(即阳性模型化合物)已被证明在小鼠和/或大鼠中诱导PLN阳性反应。几个实验室已经获得了可重复的结果,在某些情况下是盲法进行的。然而,阴性模型化合物丙酮和丙咪嗪也获得了阳性反应。流式细胞术分析和传统组织学未能帮助区分真正的GvH反应和原发性刺激效应。为了确认PLN试验预测药物诱导的类GvH反应风险的潜在价值,迫切需要进行机制研究。