Abstract: Background: Systemic juvenile idiopathic arthritis (SJIA) has a high disability rate and there are currently no specific therapeutic drugs. The efficacy of new biologic drugs developed for IL-1 or IL-6 monoclonal antibodies in some patients is not satisfactory. Further research on the pathogenesis is urgently needed to explore new treatment strategies. Objective: To explore the role of NLRP3 inflammasome and related inflammatory mediators in the pathogenesis of SJIA. Design: Case-control study. Methods: The children with SJIA in the active period were included, and the healthy children who went to the hospital for physical examination during the same period were the control group. Peripheral venous blood samples were collected from children with SJIA before glucocorticoid therapy, at 2 weeks and 8 weeks after treatment, and from healthy children during physical examination, and then peripheral blood mononuclear cells (PBMCs) were extracted. The mRNA and protein expression levels of NLRP3 and related inflammatory mediators were detected by Quantitative Rea-time-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting, respectively. Main outcome measures: Expression levels of NLRP3 and related inflammatory mediators. Results: A total of 33 children with SJIA were enrolled, aged (8.2±3.7) years. There were 28 healthy children, aged (7.6±2.7) years. Compared with healthy children, in active SJIA children there was no significant change in the mRNA level of NLRP3, but the protein expression decreased and the concentrations of IL-1β and IL-18 increased. After 2 weeks of treatment, the level of IL-1β, IL-18, IL-2, IL-10 and IFN-γ in children with SJIA all decreased, and at the 8th week of treatment, the level of IL-2, IFN-γ and IL-18 were still lower than those before treatment. The differences were statistically significant (P<0.05). Conclusion: In SJIA, IL-1β and IL-18 may not be regulated through NLRP3 inflammasomes. IL-1β and IL-18 can be used as monitoring indicators of SJIA disease activity.

Key words: NLRP3 inflammasome, Systemic juvenile idiopathic arthritis, IL-1β, IL-18