Cytokines and Absence Seizures in a Genetic Rat Model

We investigated the role of two cytokines, IL-1 beta and TNF-alpha, in the development of absence seizures using a genetic model of absence epilepsy in WAG/Rij rats. We administered these cytokines to animals systemically and measured the number of spike-wave discharges (SWDs) in the EEG. We also coadministered IL-1 beta with the GABA reuptake inhibitor tiagabine and measured the levels of IL-1 beta and TNF-alpha in the brain and blood plasma of 2-, 4-, and 6-month-old WAG/Rij rats and animals that served as a non-epileptic control (ACI). We found that IL-1 beta induced a significant increase in SWDs 2-5 h after administration, while TNF-alpha enhanced SWDs much later. Both cytokines enhanced passive behavior; body temperature was elevated only after TNF-alpha. The action of tiagabine was potentiated by earlier IL-1 beta injection, even when IL-1 beta was no longer active. Young WAG/Rij rats showed higher levels of TNF-alpha in blood serum than young ACI rats; the effects in the brain tended to be opposite. The marked differences in timing of the increase in SWDs suggest different time scales for the action of both cytokines tested. It is proposed that the results found after TNF-alpha are due to the de novo synthesis of IL-1 beta. TNF-alpha may possess neuroprotective effects. IL-1 beta might increase GABA-ergic neurotransmission. The changes in the efficacy of antiepileptic drugs related to changes in the cytokine systems may have some clinical relevance.