Antiepileptogenic and anticonvulsant activity of interleukin-1 beta in amygdala-kindled rats

Ischaemic, excitotoxic and traumatic brain injuries have been associated with the occurrence of epileptic seizures. Microglia, the principal immune cells in the brain, produce a variety of proinflammatory and cytotoxic factors especially interleukin-1 (IL-1) early after an acute insult. We studied the effect of intracerebroventricularly administered IL-1beta on seizure acquisition and on fully kindled seizures in amygdala kindling model of epilepsy. IL-1beta (0.01 ng/rat) retarded acquisition of kindled behavioral seizures and growth of afterdischarges (AD). IL-1beta (0.01-10 ng/rat) also exhibited significant anticonvulsant effect on established kindled seizures and AD duration. This effect began 0.5 h after administration and was continued up to 72 h. Pretreatment of the kindled animals with nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, or cyclooxygenase inhibitor, piroxicam, reversed the anticonvulsant effect of IL-1beta at early time points. Although most of the previous studies indicate a proconvulsant or convulsant property of IL-1, our results support a protective and antiepileptogenic role of IL-1beta.