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

• Published in: CNS neuroscience & therapeutics 2015-08, Vol.21 (8), p.642-650
• Main Authors: Tao, An‐Feng, Xu, Zheng‐Hao, Chen, Bin, Wang, Yi, Wu, Xiao‐Hua, Zhang, Jing, Tang, Yang‐Shun, Xu, Ceng‐Lin, Zhao, Hua‐Wei, Hu, Wei‐Wei, Shi, Li‐Yun, Zhang, Shi‐Hong, Chen, Zhong
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine; Animals; Disease Models, Animal; Electroshock; Epilepsy; Hippocampus - metabolism; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein - metabolism; Interleukin-1beta - administration & dosage; Interleukin-1beta - metabolism; Interleukin‐1 beta; Interleukin‐1 Receptor Type I; Kindling, Neurologic; Mice, Inbred C57BL; Mice, Knockout; Original; 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; Seizures - metabolism; Status Epilepticus - metabolism
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.12416

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‐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.