甲基强的松龙对强直性脊柱炎患者外周血IL-23/IL-17及Th17/Treg的影响

Influence of methylprednisolone on IL-23/IL-17 and Th17/Treg of peripheral blood in patients with ankylosing spondylitis

目的探讨甲基强的松龙(Methylprednisolone,MP)治疗对强直性脊柱炎(Ankylosing spondylitis,AS)患者外周血单核细胞(Peripheral blood mononuclear cells,PBMCs)IL-23、IL-17基因表达及Th17、Treg细胞分布状态的影响及意义。方法选取30例活动期AS患者为实验组,予短期大剂量MP治疗,治疗方案为2.5~4 mg/kg,Qd,每个疗程3~4 d,间隔3~4 d,2~3个疗程;选取30例正常人作为对照组,予等体积生理盐水,给药时间、方式同前。RT-PCR检测对照组及MP治疗实验组前后PBMCs IL-23 P19 m RNA、IL-17A m RNA表达水平,FCM检测PBMCs Th17、Treg细胞分布状态,分析其与临床症状、疾病活动性指标的相关性。结果 1.实验组Th17细胞分布及IL-23、IL-17基因表达治疗高于对照组,与BASDAI、夜间痛、血沉、CRP指标之间呈正相关;实验组Treg细胞分布低于对照组,与上述指标呈负相关。2.实验组Th17细胞分布、IL-23基因表达及IL-17基因表达之间互呈正相关,IL-23基因表达和Treg细胞分布呈负相关,Th17细胞分布和Treg细胞分布呈负相关;3.实验组经MP治疗后BASDAI、BASFI、夜间痛、血沉、CRP较治疗前均下降,IL-23、IL-17基因表达及Th17细胞分布较治疗前均下降,Treg细胞分布较治疗前上升;以上差异均具有统计学意义。结论 IL-23/IL-17轴、Th17/Treg细胞失衡可能参与AS的发病及病情活动,而MP可通过抑制促炎因子IL-23、IL-17分泌、纠正Th17/Treg失衡改善AS临床症状并降低疾病活动度。

Objective To investigate the influence and significance of methylprednisolone（MP） on the genetic expression and distribution of peripheral blood mononuclear cells （PBMCs） IL-23 and IL-17 as well as Thl7 and Treg in patients with ankylosing spondylitis（AS）. Methods 30 patients in the active period of AS were selected as study group and treated with short-term and high-dose MP. The treatment regimen was 2.5-4 mg/kg, Qd, 3-4 d/course, 3-4 d interval and 2-3 courses. 30 healthy persons were selected as control group and given isometric normal saline by the same administration time and method.RT-PCR test was used to assess the expression of PBMCs IL-23 P19 mRNA and IL- 17A mRNA, and FCM was used to assess the cell distributions of PBMCs Th17 and Treg in control group and study group before and after treatment. Associations of them with clinical symptoms and indicators of disease activity were analyzed. Results 1.Cell distribution of Thl7 and genetic expression of IL-23 and IL-17 in study group were higher than those in control group, and positively associated with BASDAI, hypnalgia, erythrocyte sedimentation rate（ESR） and CRP.Cell distribution of Treg in study group was lower than that in control group, and negatively associated with indicators mentioned above. 2.In study group, cell distribution of ThlT, genetic expression of IL-23 and genetic expression of IL-17 were positively associated with each other, and the genetic expression of IL-23 and the cell distribution of Th17 were negatively associated with the cell distribution of Treg respectively. 3.In study group, BASDAI, BASFI,hypnalgia,ESR and CRP after treatment were lower than those before treatment while cell distribution of Treg after treatment was higher than that before treatment. All the differences above were statistically significant. Conclusion The axis of IL-23/IL-17 and the unbalance of Th17/Treg could be involved in the attack and disease activity of AS.MP could improve the clinical symptoms of AS and reduce the disease activity by inhibiting the secretion of proinflammatory factors IL-23 and IL-17, and correcting the unbalance of Th17/Treg.