Mechanism of the promotion of GEFS+ by the STAT3-mediated expression of interleukin-6

Genetic epilepsy with febrile seizures plus (GEFS+) is generally considered an ion channelopathy. To date, there have been few studies on inflammation associated with various types of epilepsy, and it remains unclear whether the inflammatory mechanism plays a key role in epilepsy.

The purpose of this study was to analyze and compare the effect of STAT3 expression and activation differences on GEFS+ attack, and to clarify the relationship between various cytokines and GEFS+ outbreak. Inhibiting the expression of pro-inflammatory factors can further prevent GEFS+ attack, which supports that IL-6 is one of the important factors that aggravate the clinical symptoms of GEFS+. We expected to provide a theoretical basis for immunosuppressive therapy of GEFS+ and a new way for its clinical treatment.

In order to explore the role of the regulatory mechanism of immune factor expression in the pathogenesis of GEFS+, the present study detected the expression level of relevant immune factors such as interleukin-6 (IL-6) in peripheral blood of GEFS+ mice.

The cluster of differentiation 4+/cluster of differentiation 8+ (CD4+/CD8+) ratio in the GEFS+ mice was decreased, while the signal transducer and activator of transcription 3 (STAT3) was also activated and the IL-6 was upregulated. Inhibit of STAT3 can lead to the GEFS+ asymptomatically due to the downregulated IL-6, IL-1β, and complement factor H (CFH) levels. Suppression of STAT3 can also inhibited the epileptic seizures, the CD8+ T cells were declined after the IL-6 was neutralized. Conclusions: The purpose of this study was to analyze and compare the effect of STAT3 expression and activation differences on GEFS+ attack, and to clarify the relationship between various cytokines and GEFS+ outbreak. Inhibiting the expression of pro-inflammatory factors can further prevent GEFS+ attack, which supports that IL-6 is one of the important factors that aggravate the clinical symptoms of GEFS+. We expected to provide a theoretical basis for immunosuppressive therapy of GEFS+ and a new way for its clinical treatment.