Neuromodulatory role of endogenous interleukin-1β in acute seizures: Possible contribution of cyclooxygenase-2

The function of endogenous interleukin-1 beta (IL-1 beta) signaling in acute seizure activity was examined using transgenic mice harboring targeted deletions in the genes for either IL-1 beta (Il1b) or its signaling receptor (Il1r1). Acute epileptic seizure activity was modeled using two mechanistically distinct chemoconvulsants, kainic acid (KA) and pentylenetetrazole (PTZ). KA-induced seizure activity was more severe in homozygous null (-/-) Il1b mice compared to their wild-type (+/+) littermate controls, as indicated by an increase in the incidence of sustained generalized convulsive seizure activity. In the PTZ seizure model, the incidence of acute convulsive seizures was increased in both Il1b and Il1r1-/- mice compared to their respective +/+ littermate controls. Interestingly, the selective cyclooxygenase (COX)-2 inhibitor, rofecoxib, mimicked the effect of IL-1 beta deficiency on PTZ-induced convulsions in Il1r1+/+ but not -/- mice. Together, these results suggest that endogenous IL-1 beta possesses anticonvulsive properties that may be mediated by arachidonic acid metabolites derived from the catalytic action of COX-2. (C) 2011 Elsevier Inc. All rights reserved.