Liu Yuhong, Wang Shasha, Shen Lingxun, Xu Yulan
Department of Immunology and Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2010 Dec;30(6):741-5. doi: 10.1007/s11596-010-0650-y. Epub 2010 Dec 22.
The present study examined the functional profile of dendritic cells (DCs) in patients with rheumatoid arthritis (RA) and the effects of simvastatin on the function of DCs. A total of 40 patients who was recently diagnosed as having RA were equally assigned to two groups: the routine treatment group (group R) and the routine treatment plus simvastatin group (group R+S). Twenty healthy individuals served as control. The peripheral blood mononuclear cells (PBMCs) were isolated before and 4 weeks after the treatment and then cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony stimulatory factor (GM-CSF) to prepare mature DCs. The expression of co-stimulating factor CD86 on the surface of DCs was assessed by flow cytometry. And the stimulating capacity of DCs was measured by mixed lymphocyte reaction (MLR). The contents of cytokines in culture supernatants of DCs in MLR were detected by ELISA. Blood lipids and high-sensitivity C-reactive protein (hs-CRP) were detected. The relationship between the expression of CD86 and the blood CRP level was also investigated. The results showed that, as compared with the control group, the CD86 expression and the level of cytokines secreted by DCs were significantly increased in RA patients and greater stimulating capacity of DCs in MLR was demonstrated in RA patients. T lymphocytes in MLR secreted higher levels of proinflammatory cytokines (IL-2, IL-17, TNF-α and INF-γ) and lower level of anti-inflammation cytokine (IL-10). The function of DCs was markedly weakened and the level of hs-CRP and low-density lipoprotein was substantially lowered in group R+S in comparison to group R. The CD86 expression was positively correlated with hs-CRP. It was concluded that DCs in RA are highly activated and DC-initiated immune reaction may play an important role in the pathogenesis of RA. Simvastatin administration can significantly inhibit the DCs function and reduce the level of hs-CRP, indicating the suppression on inflammatory reaction may be one of the mechanisms by which simvastatin exerts its effect in treating RA.
本研究检测了类风湿关节炎（RA）患者树突状细胞（DCs）的功能概况以及辛伐他汀对DCs功能的影响。共有40例近期诊断为RA的患者被平均分为两组：常规治疗组（R组）和常规治疗加辛伐他汀组（R+S组）。20名健康个体作为对照。在治疗前和治疗4周后分离外周血单个核细胞（PBMCs），然后用白细胞介素-4（IL-4）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）培养以制备成熟DCs。通过流式细胞术评估DCs表面共刺激因子CD86的表达。并通过混合淋巴细胞反应（MLR）测量DCs的刺激能力。用ELISA检测MLR中DCs培养上清液中细胞因子的含量。检测血脂和高敏C反应蛋白（hs-CRP）。还研究了CD86表达与血液CRP水平之间的关系。结果显示，与对照组相比，RA患者DCs的CD86表达和分泌的细胞因子水平显著增加，并且在RA患者中证明了DCs在MLR中的刺激能力更强。MLR中的T淋巴细胞分泌更高水平的促炎细胞因子（IL-2、IL-17、TNF-α和INF-γ）和更低水平的抗炎细胞因子（IL-10）。与R组相比，R+S组DCs的功能明显减弱，hs-CRP和低密度脂蛋白水平大幅降低。CD86表达与hs-CRP呈正相关。得出结论，RA中的DCs被高度激活，DC启动的免疫反应可能在RA的发病机制中起重要作用。给予辛伐他汀可显著抑制DCs功能并降低hs-CRP水平，表明对炎症反应的抑制可能是辛伐他汀发挥治疗RA作用的机制之一。
