OBJECTIVE To investigate whether the transient augment of cytokine Intedeukin 1 (IL-1) in hippocampus after febrile seizures initiates molecular cascades to promote epilepto genesis.METHODS Febrile seizures (FS) were induced by exposing SD rat pups (P8-10) to a hyperthermal chamber (44± 2)℃ to raise the body temperature with stereotyped behav iors.IL-1 receptor antagonist (IL-1ra) was injected into the hip poeampus immediately, 24 h, 3 d or 7 d after FS.0.3, 1, 3and 10 ng/O.4 μ1 of IL-1 were injected alone in normal rat pups (P8-10).CB1 receptor antagonist SR141716A (ip) was ad ministered 3 d or 7 d after FS induction and IL-1 injection.When the rats were adults, their sensitivity to epilepsy was meas ured by Maximal electroshock (MES).Expression of CB1 recep tors was detected by Western Blotting at postnatal d 15 and 45,respectively.RESULTS IL-1ra administered immediately and 24 h after FS reversed the enhanced susceptibility to MES-induced seizures and upregulated the expression of CB1 receptors.IL-1 alone increased both the susceptibility to seizures and the expression of CB1 receptors till day 15 at all doses,and the dose of 1 ng showed a long-lasting effect(at least for 45 d).CB1 receptor antagonist SR141716A baolished the enhanced susceptibility to seizures.CONCLUSION Our study insicates that augmenged levdls of IL-1 in the hippocampus FS might promote epileptogendwis by,at least partly,modulating endocannabinoid signaling.