The Pro-inflammatory Cytokine Interleukin-1β Attenuates The Postictal Suppression Via Interleukin-1 Receptor In Mice

Aims:The postictal suppression (PS) is a common and important period following an epileptic seizure but has not been well studied. Increasing experimental evidence and clinical observations indicate that the PS may serve as "a double-edged sword" for epileptic patients. That is, a weakened PS may deteriorate seizures and even induce status epilepticus (SE), while a hyperactive PS may result in postictal problems and even sudden unexpected death after a seizure. So far, the underlying mechanisms of the PS are only incompletely understood, and hence there is still no reliable approach to modulating the PS in clinic. Thus, it is a pressing need to find out the regulatory targets for the PS. The production of IL-1β is increased in epileptic tissues involved in seizure generation and propagation. Experimental evidence in a variety of acute seizure models indicate that CNS IL-1β may contribute to PS. Thus the present 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 mouse seizure models induced by hippocampal kindling, maximal electroshock seizure (MES), and 4-aminopyridine, respectively.Results:IL-1RA or IL-1R1 knockout prolonged 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 period of postictal EEG suppression and seizure refractory phenomenon in IL-1R1 knockout mice. In addition,30 min after intrahippocampal injection of 4-aminopyride, IL-1β increased the incidence of status epilepticus (SE), while IL-1RA prolonged the intervals between recurrent seizures.Conclusions:The present study provides the first direct evidence that IL-1β is a key regulatory factor for the PS, and its receptor IL-1R1 may be a potential target for adjuvant treatment of postictal problems.