【摘要】 目的观察托法替尼(tofacitinib)对人外周血中单个核细胞(PBMCs)和纯化CD14+单核细胞分泌细胞因子的作用。方法本研究采集健康志愿者或幼年特发性关节炎患儿肝素抗凝静脉血,Ficoll密度梯度离心法分离PBMCs并纯化CD14+单核细胞,应用抗CD3抗体联合CD28抗体、LPS或CPG进行刺激,加或不加入托法替尼培养,检测IFN-γ、IL-1β和IL-6的产生。结果在健康志愿者和幼年特发性关节炎患儿中,托法替尼都可以抑制PBMCs产生IFN-γ,但促进PBMCs产生IL-1β和IL-6;进一步研究的结果表明托法替尼促进纯化CD14+单核细胞分泌IL-1β和IL-6。结论托法替尼抑制T细胞IFN-γ的产生,但促进单核细胞IL-1β和IL-6的分泌,提示托法替尼对T细胞和单核细胞细胞因子分泌存在相反作用。不同类型JIA的发病机制涉及不同的免疫细胞,因此,需要进一步研究托法替尼对各型JIA的疗效是否存在差异,以期为托法替尼的临床应用提供参考。更多还原

【Abstract】 This study was performed to observe the effects of tofacitinib on the secretion of cytokines by human peripheral blood mononuclear cells(PBMCs) and purified CD14+monocytes. PBMCs from healthy volunteers or children with juvenile idiopathic arthritis were isolated by ficoll-hypague density gradient centrifugation and CD14+monocytes were sorted by immunomagnetic beads. Human PBMCs and purified CD14+monocytes were stimulated with anti-CD3 plus anti-CD28, LPS or CPG in the presence or absence of tofacitinib. The levels of IFN-γ, IL-1βand IL-6 in the culture supernatants were detected by ELISA. The expression levels of IL-1β and IL-6 were analyzed by FACS. Data showed that tofacitinib could inhibit the production of IFN-γ, but promote the production of IL-1β and IL-6 by PBMCs of both healthy volunteers and children with juvenile idiopathic arthritis. Further studies indicated that tofacitinib could promote the secretion of IL-1β and IL-6 by purified CD14+monocytes. All these results indicated that tofacitinib inhibits the production of IFN-γ by T cells, but promotes the secretion of IL-1βand IL-6 by monocytes, suggesting that tofacitinib has opposite effects on cytokine secretion of T cells and monocytes. As the pathogenesis of different types of JIA varies, the further study on the efficacy of tofacitinib on different types of JIA is of great significance for the clinical application of tofacitinib.更多还原