IL-6抗体对银屑病小鼠的治疗作用及其对外周血辅助性T细胞和树突状细胞影响的研究

Therapeutic Effect of IL-6 Antibody on Psoriatic Mice and its Effect on Peripheral Blood Helper T Cells and Dendritic Cells

目的:研究白介素-6(Interleukin-6,IL-6)抗体对银屑病小鼠的治疗作用,并探讨IL-6抗体治疗对银屑病小鼠外周血辅助性T细胞和树突状细胞影响。方法:30只6-8周龄SPF级BALB/c小鼠按照随机数字表法分为Normal组、Model组和IL-6组,Model组和IL-6组小鼠通过在背部脱毛区涂抹咪喹莫特建立银屑病小鼠模型。IL-6组小鼠通过在背部脱毛区皮下注射IL-6抗体进行治疗。比较三组小鼠皮损组织银屑病皮损面积及严重程度指数(psoriasis area and severity index,PASI)、表皮厚度和血管数、血清TNF-α、IL-17和IL-23含量、外周血树突状细胞、Th17细胞和Th22细胞比例以及皮损组织IL-6、IL-21和STAT3蛋白表达。结果:IL-6抗体治疗后,Model组和IL-6组小鼠皮损组织PASI、表皮厚度和血管数,血清TNF-α、IL-17和IL-23含量,外周血树突状细胞、Th17细胞和Th22细胞比例,以及皮损组织IL-6、IL-21和STAT3蛋白表达均显著高于Normal组小鼠(P<0.05);与Model组相比,IL-6组小鼠皮损组织PASI、表皮厚度和血管数,血清TNF-α、IL-17和IL-23含量,外周血树突状细胞、Th17细胞和Th22细胞比例,以及皮损组织IL-6、IL-21和STAT3蛋白表达均显著降低(P<0.05)。结论:IL-6抗体对银屑病小鼠模型具有较好的治疗作用,其机制可能与通过抑制IL-6/STAT3通路影响Th17/Th22和树突状细胞水平有关。

Objective:To study the therapeutic effect of IL-6 antibody on psoriatic mice,and to explore the effect of IL-6 antibody treatment on peripheral blood helper T cells and dendritic cells of psoriatic mice.Methods:Thirty 6-8 week old SPF grade BALB/c mice were divided into Normal group,Model group and IL-6 group according to the random number table method.The Model group and IL-6 group were used to establish psoriasis mouse models by applying imiquimod.Mice in the IL-6 group were treated by subcutaneous injection of IL-6 antibody in the dorsal alopecia.The psoriasis area and severity index(PASI),epidermal thickness and number of blood vessels in the skin lesions of the three groups of mice were compared,serum TNF-α,IL-17 and IL-23 levels,peripheral blood dendritic cells,Th17 cells and Th22 cells ratios and IL-6,IL-21 and STAT3 protein expressions in skin lesions.Results:After IL-6 antibody treatment,PASI,epidermal thickness and blood vessel number,serum TNF-α,IL-17 and IL-23 contents,peripheral blood dendritic cells and Th17 cells of mice in Model group and IL-6 group were compared.The proportions of IL-6,IL-21 and STAT3 in skin lesions were significantly higher than those in the Normal group(P<0.05);compared with the Model group,the PASI in the skin lesions of the IL-6 group mice,epidermal thickness and blood vessel number,serum TNF-α,IL-17 and IL-23 levels,peripheral blood dendritic cells,Th17 cells and Th22 cell ratios,and IL-6,IL-21 and STAT3 protein expressions in skin lesions were significantly decreased(P<0.05).Conclusion:IL-6 antibody has a good therapeutic effect on the psoriasis mouse model,and its mechanism may be related to the influence of Th17/Th22 and dendritic cell levels by inhibiting the IL-6/STAT3 pathway.