[Effects of antiepileptic drugs on immune system]

Abstract

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.