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

Robert J. Claycomb, Sandra Hewett, James Hewett

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The function of endogenous interleukin-1β (IL-1β) signaling in acute seizure activity was examined using transgenic mice harboring targeted deletions in the genes for either IL-1β (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-1β deficiency on PTZ-induced convulsions in Il1r1+/+ but not -/- mice. Together, these results suggest that endogenous IL-1β possesses anticonvulsive properties that may be mediated by arachidonic acid metabolites derived from the catalytic action of COX-2.

Original languageEnglish (US)
Pages (from-to)234-242
Number of pages9
JournalNeurobiology of Disease
Volume45
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

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Keywords

  • Acute seizures
  • Cyclooxygenase-2
  • Epilepsy
  • Interleukin-1 receptor type 1
  • Interleukin-1β
  • Kainic acid
  • Knockout mice
  • Pentylenetetrazole
  • Rofecoxib

ASJC Scopus subject areas

  • Neurology

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