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

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.