Epilepsy and pro-inflammatory cytokines. Immunomodulating properties of antiepileptic drugs

Epilepsy is a complex and multifactorial phenomenon. Accumulating evidence suggests that the immune system may play an important role in neuronal excitability and epileptogenesis. In many animal models of epilepsy, seizures induced chemically or electrically cause glial activation and increased expression of pro-inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6). The studies show that the IL-1 beta/IL-1Ra system may modulate epileptic activity and contribute to neuronal excitability Exogenous IL-1 beta has pro-convulsive properties. The action of TNF-a and IL-6 is complex (either stimulating or inhibitory action of these cytokines on seizures, depending on their concentration and the type of receptors involved in the response). In vitro and in vivo experiments show that antiepileptic drugs could affect cytokine levels (e.g. valproate significantly inhibited production of TNF-a and IL-6 by human monocytic leukaemia cells). In epilepsy patients studies (in-cluding ex vivo) show elevated levels of IL-1 beta, IL-2, IL-5, IL-6 or TNF-alpha after carbamazepine, valproic acid and phenytoin. This review surveys the current state of knowledge regarding effects of pro-inflammatory cytokines on seizure pathogenesis. Cytokine modulatory actions of some antiepileptic drugs are also discussed.