Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production

An enhanced production of IL-1 beta in glia is a typical feature of epileptogenic tissue in experimental models and in human drug-refractory epilepsy. We show here that the selective inhibition of Interleukin Converting Enzyme (ICE), which cleaves the biologically active form of IL-1 beta using VX-765, blocks kindling development in rats by preventing IL-1 beta increase in forebrain astrocytes, without interfering with glia activation. The average afterdischarge duration was not altered significantly by VX-765. Up to 24 h after kindling completion and drug washout, kindled seizures could not be evoked in treated rats. VX-765 did not affect seizures or afterdischarge duration in fully kindled rats. These data indicate an antiepileptogenic effect mediated by ICE inhibition and that specific anti-IL-1 beta pharmacological strategies can be envisaged to interfere with epileptogenic mechanisms. (C) 2008 Elsevier Inc. All rights reserved.