Gabourel J D, Davies G H, Bardana E J, Ratzlaff N A
Epilepsia. 1982 Aug;23(4):367-76. doi: 10.1111/j.1528-1157.1982.tb05422.x.
The results of this prospective study fail to confirm previously reported phenytoin suppression of lymphocyte responsiveness to mitogens. Our data show a significantly greater than expected percentage (p less than 0.0001) of patients requiring phenytoin treatment have low lymphocyte responsiveness to mitogens prior to phenytoin therapy. Analysis of changes in each individual's response during phenytoin treatment as compared with their pre-phenytoin responses shows a consistent trend to increased responsiveness to concanavalin A, pokeweed mitogen, and to a suboptimal concentration of phytohemagglutinin. This trend was most pronounced for patients whose serum IgA concentration was decreased while taking phenytoin, whereas there was no such trend for individuals whose serum IgA levels were not decreased. This phenomenon was not related to neurological disease classification. Phenytoin added directly to lymphocyte cultures depressed lymphocyte responses to all mitogens in a small (less than 20%) but significant degree, confirming similar in vitro studies by other investigators. Because of limited serum proteins for phenytoin binding in culture medium, these in vitro studies have little application to possible phenytoin effects on lymphocytes of patients taking it to prevent seizures. Thus, the suggestion that phenytoin causes depressed lymphocyte responses to mitogens in epileptic patients appears unwarranted.
这项前瞻性研究的结果未能证实先前报道的苯妥英对淋巴细胞对有丝分裂原反应性的抑制作用。我们的数据显示，在接受苯妥英治疗的患者中，淋巴细胞对有丝分裂原的反应性低于预期的比例显著更高（p小于0.0001），这些患者在接受苯妥英治疗前淋巴细胞对有丝分裂原的反应性就较低。分析每个个体在苯妥英治疗期间与治疗前反应相比的变化，结果显示对刀豆球蛋白A、商陆有丝分裂原和次优浓度的植物血凝素的反应性呈持续增加的趋势。对于服用苯妥英期间血清IgA浓度降低的患者，这种趋势最为明显，而对于血清IgA水平未降低的个体则没有这种趋势。这种现象与神经疾病分类无关。直接添加到淋巴细胞培养物中的苯妥英在较小程度（小于20%）但显著地抑制了淋巴细胞对所有有丝分裂原的反应，这证实了其他研究者的类似体外研究结果。由于培养基中用于苯妥英结合的血清蛋白有限，这些体外研究对于服用苯妥英预防癫痫发作的患者的淋巴细胞可能产生的苯妥英效应几乎没有应用价值。因此，认为苯妥英会导致癫痫患者淋巴细胞对有丝分裂原的反应性降低的说法似乎没有依据。
