Anticonvulsant-induced suppression of IFN-gamma production by lymphocytes obtained from cervical lymph nodes in glioma-bearing mice

It is well known that phenytoin can cause impairment of cellular immunity. The authors investigated the potential role of other anticonvulsant drugs i n the development of antitumor immunity in murine malignant glioma models. The survival rate was determined in murine glioma models using syngeneic 20 3 glioma cells following treatment with four anticonvulsants, which are mos t commonly administered to glioma patients, i.e., phenytoin, phenobarbital, valproate and zonisamide. In a second set of experiments, we further exami ned the effect of these drugs on interferon-gamma (IFN-gamma) secretion by lymphocytes prepared from cervical lymph nodes (CLN) in the same models. Th e IFN-gamma production of CLN lymphocytes as measured by ELISA method was m arkedly impaired in the early stage of tumor-bearing mice treated with phen ytoin or zonisamide, and the median survival time (MST) of controls and of mice treated with either phenytoin or zonisamide was 13, 10 and 11 days, re spectively, which was not a statistically significant difference. Phenobarb ital and valproate did not affect either IFN-gamma production or their surv ival rate. In addition, immunohistochemistry showed a reduction in tumor-in filtrating lymphocytes containing CD4 and CD8 antigens in the mice treated with phenytoin and zonisamide. Two anticonvulsants, phenytoin and zonisamide, showed a significant inhibit ory effect on IFN-gamma production by CLN lymphocytes in murine glioma mode ls, although there was no statistically significant difference in MST betwe en controls and the anticonvulsant-treated mice. These drugs might have som e detrimental influence on the prognosis of brain tumor patients when combi ned with the latent immune dysfunction accompanying the tumor-bearing state .