THE POPLITEAL LYMPH-NODE ASSAY - A TOOL FOR STUDYING THE MECHANISMS OF DRUG-INDUCED AUTOIMMUNE DISORDERS

THE POPLITEAL LYMPH-NODE ASSAY - A TOOL FOR STUDYING THE MECHANISMS OF DRUG-INDUCED AUTOIMMUNE DISORDERS
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DOI:
10.1016/0378-4274(92)90178-m
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发表时间:
1992-12-01
期刊:
影响因子:
3.5
通讯作者:
DESCOTES, J
DESCOTES, J
中科院分区:
医学3区
文献类型:
--
作者:
DESCOTES, J

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虽然目前尚不能预测动物体内器官特异性药物所致自身免疫性疾病的风险,但大量证据表明,小鼠或大鼠的延髓淋巴结检测(PLNA)有助于预测全身药物所致的自身免疫性疾病。用酶诱导剂对动物进行的研究表明,在少数情况下可能涉及代谢物而不是母体分子。组织学检查有助于区分主要刺激物、接触性致敏剂和“自身免疫”化合物。这可能涉及移植物抗宿主(GVH)样机制,这一发现进一步证实了PLNA阳性反应的组织学特征。链脲佐菌素,与“真正的”局部GVH反应非常相似。此外,通过研究PLN淋巴细胞亚群和释放的细胞因子的分布,该模型有望有助于我们更好地理解(S)参与全身自身免疫反应的机制。
Whereas it is still impossible to predict the risk for organ-specific drug-induced autoimmune disorders in animals, a large body of evidence suggests that the popliteal lymph node assay (PLNA) in mice or rats is instrumental to predict systemic drug-induced autoimmune disorders. Metabolites may be involved instead of the parent molecules in a few instances as shown by studies using animals pretreated with enzyme inducers. Histological examination can help distinguish primary irritants, contact sensitizers and 'autoimmunogenic' compounds. That a Graft-vs-Host (GvH)-like mechanism may be involved was further substantiated by the finding that histological features of a positive PLNA response to, eg. streptozotocin, were quite similar to those of a 'true' local GvH response. In addition, this model is expected to be useful to improve our understanding of the mechanism(s) involved in systemic autoimmune reactions by studying the profile of PLN lymphocyte subpopulations and of released cytokines.