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Neurobiol Dis. 2008 Sep;31(3):327-33. doi: 10.1016/j.nbd.2008.05.007. Epub 2008 May 29.

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

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Department of Neuroscience, Laboratory of Experimental Neurology, Mario Negri Institute for Pharmacological Research, Milano, Italy.


An enhanced production of IL-1beta 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-1beta using VX-765, blocks kindling development in rats by preventing IL-1beta 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 suggest that specific anti-IL-1beta pharmacological strategies can be envisaged to interfere with epileptogenic mechanisms.

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