甲泼尼龙治疗难治性强直性脊柱炎对Th1/Th2细胞及其细胞因子的影响

Effect of Methylprednisolone on the Th1/Th2 Balance and Cytokines in Patients with Refractong Ankylosing Spondylitis

目的探讨甲泼尼龙对难治性强直性脊柱炎(ankylosing spondylitis,AS)患者外周血T辅助(T helper, Th)细胞活化状态及其细胞因子分泌的影响。方法用三色流式细胞分析法对AS患者治疗前后和正常对照组外周血淋巴细胞胞内细胞因子(IFN-γ、TNF-α及IL-4)和Th1、Th2细胞进行分析,同时采用夹心酶联免疫吸附法测定血清IFN-γ、TNF-α及IL-4水平,分析其与临床疗效指标的相关性。结果难治性AS患者外周血Th1细胞百分率及血清IFN-γ,TNF-α水平高于正常对照组(P<0.05),与BASDAI、BASFI、BASMI评分、夜间痛、血沉和C反应蛋白呈正相关(P<0.05);Th2细胞百分率及血清IL-4低于正常对照组(P>0.05),与以上疗效评价指标呈负相关(P<0.05)。甲泼尼龙治疗后Th1细胞百分率及血清IFN-γ、TNF-α水平较治疗前明显降低,Th2细胞百分率和血清IL-4较治疗前升高。结论难治性AS患者外周血淋巴细胞存在Th1和Th2细胞平衡偏移,Th1细胞占优势。甲泼尼龙治疗可下调Th1细胞功能,抑制促炎因子IFN-γ、TNF-α分泌,并能显著改善AS患者的关节症状和疾病活动性。

Objective To study expression of Th cells and cytokines in peripheral blood from patients of refractong ankylosing spondylitis （AS） and their changes after treated by Methylprednisolone （MP）. Methods Threecolor flow cytometric analysis was employed for intraceilular cytokines （IFN-γ, TNF-α and IL-4） and Th ceils in the peripheral blood of refractong intractable AS patients and healthy volunteers. Sandwich ELISA was used to measure the level of cytokines （IFN-γ, TNF-α and IL-4） in the serum. Besides, correlations between them and generally accepted international criterion were evaluated. Results Percentages of Thl ceils and concentration of serum cytokines （IFN-γ and TNF-α） from intractable AS patients were higher than these of healthy volunteers. They had positive correlation with criterion （BASDAI, BASFI, BASMI, night pain, ESR and CRP）. Percentage of Th2 cells and serum concentration of IL-4 were low. And, serum IL-4 was negatively correlated with criterion above. Percentage of Thl ceils and concentration of serum cytokines （IFN-γ and TNF-α） were decreased as well as percentage of Th2 ceils and serum concentration of IL-4 were increased. Conclusions Thl subset plays the dominant role where Th cells subsets are significantly abnormal in the peripheral blood of the intractable AS patients. MP can induce a down-regulation of Thl cells and inhibit proinflammatory factor （IFN-γ, TNF-α. So the way of MP treatment on intractable AS patients can be considered.