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 groups 31 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.