Basta-Kaim Agnieszka, Budziszewska Bogusława, Lasoń Władysław
Zaklad Neuroendokrynologii Doswiadczalnej, Instytut Farmakologii Polskiej Akademii Nauk w Krakowie.
Przegl Lek. 2008;65(11):799-802.
Increasing body of evidence indicate that besides the central nervous system, antiepileptic drugs may also affect the immunoactivity. Experimental data showed that classical antiepileptic drugs affect peripheral immunological parameters. To this end, phenytoin and carbamazepine attenuate both humoral and cellular response, and an engagement of CD8+ cells in these effects was suggested. Other authors reported that valproate and phenobarbital diminished humoral response and lymphocyte T cytotoxicity in mice, respectively. On the other hand, withdrawal of carbamazepine and phenytoin enhanced autoimmune response in experimental encephalomyelitis in mice. Few data concern effects of new antiepileptic drugs on immune system. It was found that topiramate reversed seizures-induced decrease in lymphocyte T proliferative activity in rats. Some new antiepileptic drugs, e.g., felbamate, stiripentol, loreclezole and tiagabine suppress mitogenes-stimulated proliferative activity of mouse splenocytes in vitro. Results of clinical studies indicate that phenytoin, carbamazepine, and valproate, show immunosuppressive activity, inhibit protein synthesis in lymphocytes, decrease CD4+/CD8+ ratio, decrease IgA, and induce changes in IgG and IgM plasma levels. Cytokine synthesis is also affected by antiepileptic drugs, although in a complex manner. Carbamazepine inhibits IL-2 and IL-4 but stimulates IL-10 and TGFb production in vitro. Treatment of epileptic patients with carbamazepine increases IL-2 level, whereas phenytoin elevates IL-1 blood concentration. In vitro valproate inhibits TNFa and IL-6 production, whereas in epileptic patients this drug enhances IL-1, IL-6 and IL-5 concentration. With respect to undesired effects of antiepileptic drugs, lamotrigine, carbamazepine, phenobarbital and phenytoin may induce hypersensitivity of immune system. The suggested mechanism of the hypersensitivity involves activation of drug specific CD4+ and CD8+, increase in IL-4 and IL-5 level, receptor T polymorphism or direct interaction of drug with lymphocyte T receptors. Summing up, majority of antiepileptic drugs show immunosuppressive effects, however under certain conditions they can also stimulate immune system. Further studies on chronic administration of traditional and new antiepileptic drugs on immune system activity are warranted.
越来越多的证据表明，除中枢神经系统外，抗癫痫药物可能还会影响免疫活性。实验数据显示，传统抗癫痫药物会影响外周免疫参数。为此，苯妥英钠和卡马西平会减弱体液免疫和细胞免疫反应，并提示CD8 +细胞参与了这些作用。其他作者报道，丙戊酸盐和苯巴比妥分别降低了小鼠的体液免疫反应和淋巴细胞T细胞毒性。另一方面，停用卡马西平和苯妥英钠会增强小鼠实验性脑脊髓炎中的自身免疫反应。关于新型抗癫痫药物对免疫系统影响的数据较少。研究发现，托吡酯可逆转癫痫发作引起的大鼠淋巴细胞T增殖活性下降。一些新型抗癫痫药物，例如非氨酯、司替戊醇、氯雷唑和噻加宾，在体外可抑制丝裂原刺激的小鼠脾细胞增殖活性。临床研究结果表明，苯妥英钠、卡马西平和丙戊酸盐具有免疫抑制活性，可抑制淋巴细胞中的蛋白质合成，降低CD4 + / CD8 +比值，降低IgA水平，并引起IgG和IgM血浆水平的变化。细胞因子的合成也受到抗癫痫药物的影响，尽管方式较为复杂。卡马西平在体外可抑制IL-2和IL-4，但可刺激IL-10和TGFb的产生。用卡马西平治疗癫痫患者可提高IL-2水平，而苯妥英钠可提高血液中IL-1的浓度。在体外，丙戊酸盐可抑制TNFa和IL-6的产生，而在癫痫患者中，该药物可提高IL-1、IL-6和IL-5的浓度。关于抗癫痫药物的不良反应，拉莫三嗪、卡马西平、苯巴比妥和苯妥英钠可能会诱发免疫系统过敏。过敏反应的推测机制包括药物特异性CD4 +和CD8 +的激活、IL-4和IL-5水平的升高、T受体多态性或药物与淋巴细胞T受体的直接相互作用。综上所述，大多数抗癫痫药物具有免疫抑制作用，但在某些情况下它们也可以刺激免疫系统。有必要对传统和新型抗癫痫药物长期给药对免疫系统活性的影响进行进一步研究。
