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

Summary 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-1[beta] (IL-1[beta]) is involved in the PS. Methods The effects of IL-1[beta] 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-1[beta] attenuated the seizure refractory phenomenon without affecting the severity of the preceding seizures in hippocampal kindling model, while IL-1RA enhanced it. Besides, IL-1[beta] reduced the postictal EEG suppression period, while IL-1RA prolonged it. And IL-1[beta] 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-1[beta] increased the incidence of SE, while IL-1RA prolonged the intervals between recurrent seizures. Conclusions This study provides the first direct evidence that IL-1[beta] is key regulatory factor for the PS, and its receptor IL-1R1 may be a potential target for adjuvant treatment of postictal problems.