The efficacy of tocilizumab treatment for one year and its effect on the Janus kinase/signal transducer and activator of transcription signaling pathway in systemic juvenile idiopathic arthritis patients / 中华风湿病学杂志

ABSTRACT

Objective By studying the efficacy of interleukin (IL)-6 receptor antagonist (tocilizumab) on acute inflammation of systemin juvenile id-iopathic arthritis (sJIA) and its effect on the downstream signaling pathways and inflammatory factors of IL-6 to further reveal the role of tocilizumab in sJIA.Methods From December 2015 to December 2018,64 sJIA children were randomly divided into two groups31 cases who were treated with tocilizumab+ glucocorticoid+disease-modifying anti-rheumatic drugs (DMARDs) as the tocilizumab group,33 cases who were treated with placebo (vitamin C) + glucocorticoid+DMARDs as the control group.They were treated for one year.The levels of IL-2,IL-4,IL-6,IL-10 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA).The expressions of p65 and receptor activator for nuclear factor-κB ligand (RANKL) in peripheral blood mononuclear cells (PBMCs) were detected by quantitative polymerase chain reaction (qPCR).The expressions of signal transducer and activator of transcription (STAT3)/phosphates signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signaling 3 (SOCS3) before and after treatment were detected by Western blotting.The differences between groups were analyzed by variance analysis.Normal distributed data was tested by K-W test.Twenty normal control subjects came from the pediatric clinic in our hospital.Results There was no significant difference in the demographic data between the two groups (P＞0.05).Among them,2 children who were treated with tocilizumab dropped out after one month treatment and three months due to un-affordability respectively.The C-reactive protein (CRP),ferritin (FER),erythrocyte sedimentation rate (ESR) in the tocilizumab treatment group decreased significantly after 6 months and 1 year when compared with the disease control group.The concentration of IL-6 in the tocilizumab group (77±46) pg/ml,control group (82±40) pg/ml were higher than that in the healthy control group (10±3) pg/ml (F=4.683,P=0.001;F=2.581,P=0.03).After one year,the concentration of IL-6 (316±42) pg/ml in the tocilizumab group was higher than that in the disease control group (62±40) pg/ml (F=11.2,P=0.001).The expression of RANKL and p65 mRNA in treatment group was significantly higher than that in healthy control group (K-W=10.03,P＜0.01;K-W=9.42,P＜0.01).After one year,the expression of RANKL and p65 mRNA in treatment group was lower than that in disease control group (K-W=9.964,P＜0.01;K-W=10.75,P＜0.01).The expression of STAT3/p-STAT3/SOCS3 in disease control group before medication was significantly higher than that in healthy control group,while the expression of p-STAT3/SOCS3 in the treatment group was significantly higher than that in healthy control group.The expression of STAT3/p-STAT3 in the tocilizumab group was significantly lower than that in the disease control group (K-W=12.54,P＜0.01;K-W=10.52,P＜0.01).Conclusion Tocilizumab can effectively alleviate the symptoms of sJIA in active phase,down-regulate the expression of STAT3/p-STAT3 protein,thereby reducing the transcription of downstream nuclear factor (p65,RANKL) mRNA,thereby affecting the proliferation of synovial cells and reducing bone destruction,but has no significant effect on the secretion of IL-6.