The Pro-inflammatory Cytokine Interleukin-1β is a Key Regulatory Factor for the Postictal Suppression in Mice

CNS Neurosci Ther. 2015 Aug;21(8):642-50. doi: 10.1111/cns.12416. Epub 2015 Jun 20.

Abstract

Aims: The postictal suppression (PS) is a common and important period following an epileptic seizure but has not been well studied. This study was designed to determine whether interleukin-1β (IL-1β) is involved in the PS.

Methods: The effects of IL-1β on the PS were tested in three independent seizure models induced by hippocampal kindling, maximal electroshock seizure (MES), and 4-aminopyridine, respectively.

Results: IL-1R1 knockout or IL-1RA enhanced the seizure refractory phenomenon without influencing the baseline seizure threshold in intermittent MES model. IL-1β attenuated the seizure refractory phenomenon without affecting the severity of the preceding seizures in hippocampal kindling model, while IL-1RA enhanced it. Besides, IL-1β reduced the postictal EEG suppression period, while IL-1RA prolonged it. And IL-1β showed no further effect on the postictal EEG suppression and seizure refractory phenomenon in IL-1R1 knockout mice. In addition, 30 min after intrahippocampal injection of 4-aminopyridine, IL-1β increased the incidence of SE, while IL-1RA prolonged the intervals between recurrent seizures.

Conclusions: This study provides the first direct evidence that IL-1β is key regulatory factor for the PS, and its receptor IL-1R1 may be a potential target for adjuvant treatment of postictal problems.

Keywords: Epilepsy; Inflammation; Interleukin-1 Receptor Type I; Interleukin-1 beta; Seizures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine
  • Animals
  • Disease Models, Animal
  • Electroshock
  • Hippocampus / metabolism
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / metabolism*
  • Interleukin-1beta / administration & dosage
  • Interleukin-1beta / metabolism*
  • Kindling, Neurologic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-1 Type I / antagonists & inhibitors
  • Receptors, Interleukin-1 Type I / genetics
  • Receptors, Interleukin-1 Type I / metabolism*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / metabolism
  • Seizures / metabolism*
  • Status Epilepticus / metabolism

Substances

  • IL1B protein, human
  • IL1B protein, mouse
  • IL1R1 protein, mouse
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Receptors, Interleukin-1 Type I
  • Recombinant Proteins
  • 4-Aminopyridine