柳氮磺吡啶对类风湿关节炎患者外周血来源的树突状细胞免疫活性的影响

Salicylazosulfapyridine Inhibits Maturation and Function of Dendritic Cell Derived from Peripheral Blood Mononuclear Cell of Patients with Rheumatoid Arthritis

研究柳氮磺吡啶(salicylazosulfapyridine,SASP)对类风湿关节炎患者外周血来源的树突状细胞(dendritic cell,DC)免疫活性的影响,探讨SASP治疗类风湿关节炎的作用机制。分离18例类风湿关节炎病人外周血单核细胞(peripheral blood mononuclear cell,PBMC),分别在DC分化成熟的不同阶段加入SASP,流式细胞仪检测DC表型的改变;混合淋巴细胞反应检测DC对同种异体T细胞的刺激作用;酶联免疫吸附实验检测IL-12的表达。实验发现SASP不影响PBMC经GM-CSF和IL-4诱导向未成熟DC的分化;但影响未成熟DC在TNF-α刺激下的成熟;抑制DC刺激同种异体T细胞增殖和分泌IL-12的能力。结果提示SASP的抗风湿作用可能与其抑制DC成熟及IL-12分泌有关。

Dendritic cell （DC） play a pivotal role in RA pathogenesis. To understand therapeutic mechanism of salicylazosulfapyridine （SASP） in rheumatoid arthritis （RA）, the affect of SASP on DC was investigated. Peripheral blood mononuclear cells （PBMC） isolated from 18 patients with RA were stimulated by GM-CSF, IL-4 to develop into immature DC. They can finally differentiate into mature DC in the presence of TNF-α. Compared with these DC, SASP-treated DC showed lower levels of CD86 and HLA-DR expression and less capacity of stimulating T cell proliferation. We found that SASP could inhibit DC maturation, but not development of DC precursor from PBMC. Moreover, the abilities of mature DC to stimulate T cell proliferation and produce IL-12 could also be restricted by SASP. This suggests that the therapeutic effect of SASP on RA maybe associated with its ability of inhibiting DC maturation, immune activity and IL-12 secretion.