Phenytoin influence on human lymphocyte mitogen response: a prospective study of epileptic and nonepileptic patients

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.