The Role Of NLRP3 Inflammation In Febrile Seizures In Childhood Through Caspase-1/IL-1β Signal Pathway

Objective:Febrile seizures(FS) is one of the most common diseases of the nervous system.Repeated seizures can cause hippocampal damage in children，which is a high-risk factor for secondary temporal lobe epilepsy.However,the causes of seizures and recurrence are complex,and the pathogenesis is not fully understood.IL-1βis proposed to play an important role in the development of FS,from in vitro data and data from peripheral blood samples.IL-1β secretion is needed for activation of the NLR family,pyrin-domain containing 3(NLRP3)inflammasome and Caspase-1.However,whether NLRP3/Caspase-lplay a role in the development ofFS remains unknown.Therefore,the purpose of this study was to analyze and explore the role of NLRP3/Caspase-1/IL-1β signaling pathway in FS in children,providing new therapeutic targets to prevent the recurrence of FS in children and FS progresses to epilepsy.Methods:A cohort of 103 cases was recruited.The patients were from the department of pediatrics,Affiliated Foshan Maternity&Child Healthcare Hospital,Southern Medical Universityfrom November 2018 to August 2020.Fifty-five FS cases and forty-eight matched controls were included in this study.Control samples were collected from children with febrile illness without seizures.We detected their levels of NLRP3,Caspase-1,and IL-1β and by Enzyme linked immunosorbent assay and/or Western blot.SPSS software was used to analyze the differences of NLRP3,Caspase-1 and IL-1βexpression in peripheral blood of children in the two groups and the correlation among NLRP3,Caspase-1 and IL-1β.Results:NLRP3 protein levels of peripheral blood mononuclear cellswere significantlyhigher in typical FS than in fever only controls(P<0.05).Additionally,serum Caspase-1 and IL-1βlevels were significantly higher in FS patients than in fever only controls(P<0.05).Moreover,serum levels of IL-1β were significantly correlatedwith levels of NLRP3 protein(r=0.787,P<0.001).NLRP3 protein levels of peripheral blood mononuclear cellswere significantly correlated with Caspase-1 levels(r=0.941,P<0.001);serum Caspase-1 levels were significantly correlated with IL-1 βlevels(r=0.945,P<0.001).Conclusions:In this study,our results indicated that NLRP3,Caspase-1,and IL-1βlevels of peripheral blood had significantly associations with typical FS of children,NLRP3,Caspase-1,and IL-1βlevels of peripheral blood showed significantpositive correlations with each other,therefore,increased NLRP3 can mediate IL-1β secretionbyCaspase-1that is responsible for the occurrence of FS.