Changes in the pattern of cytokine production from peripheral blood mononuclear cells in patients with rheumatoid arthritis treated with infliximab and their relation to plasma arginase activity
Changes in the pattern of cytokine production from peripheral blood mononuclear cells in patients with rheumatoid arthritis treated with infliximab and their relation to plasma arginase activity
复制标题
英夫利昔单抗治疗类风湿性关节炎患者外周血单核细胞细胞因子产生模式的变化及其与血浆精氨酸酶活性的关系
DOI：
10.1111/1756-185x.12864
复制
发表时间：
2016
影响因子：
2.5
通讯作者：
Kojiro Sato and Toshihide Mimura
中科院分区：
文献类型：
--
作者：
Fumihiko Miyoshi;Kojiro Sato and Toshihide Mimura
目的本研究的目的是量化的T细胞的细胞因子的产生从RA患者的外周血单个核细胞（PBMC）前和后与抗肿瘤坏死因子（TNF）-α英夫利昔单抗（IFX）。方法我们刺激RA患者的PBMC（n= 24）在体外和定量的细胞因子在培养上清液中使用酶联免疫吸附试验。结果出乎意料的是，测试的细胞因子，干扰素（IFN）-γ，白细胞介素（IL）-4和IL-17在治疗后均增加，而不是减少。当根据与髓源性抑制细胞的免疫抑制功能有关的凝血酶的血浆活性将患者分为两组时，仅在IFX治疗后凝血酶活性降低的组中检测到细胞因子体外产生的显著增加。事实上，虽然theex vivo生产的IL-21增加沿着与其他细胞因子，IL-21的血浆浓度显着下降IFX treatment.ConclusionIt后，重要的是要谨慎解释ex vivo细胞因子生产数据，因为它们可以产生负面影响的免疫抑制机制，防止过度炎症。因此，为了准确地分析T细胞应答，需要发现血清或血浆中可检测的T细胞标志物。IFN-γ、IL-4和IL-17的浓度均低于检测限，但IL-21的浓度在血浆中可检测到，且与离体IL-21的产生呈负相关。提示Th 17反应参与了RA的发病过程。
AimThe aim of this study was to quantify the production of T‐cell cytokines from the peripheral blood mononuclear cells (PBMCs) of RA patients before and after treatment with anti‐tumor necrosis factor (TNF)‐α infliximab (IFX).MethodWe stimulated the PBMCs of RA patients (n= 24)in vitroand quantified the cytokines in the culture supernatant using enzyme‐linked immunosorbent assay.ResultsUnexpectedly, the cytokines tested, interferon (IFN)‐γ, interleukin (IL)‐4 and IL‐17, were all found to have increased, rather than decreased, after the treatment. When the patients were divided into two groups according to the plasma activity of arginase, which is implicated in the immune‐suppressive function of myeloid‐derived suppressor cells, the substantial increase in the cytokine productionex vivowas only detected in the group in which the arginase activity was decreased after the treatment with IFX. In fact, although theex vivoproduction of IL‐21 increased along with the other cytokines, the plasma concentration of IL‐21 decreased significantly after IFX treatment.ConclusionIt is important to exercise caution in interpretingex vivocytokine production data, in that they can be negatively influenced by the immune‐suppressive mechanisms that prevent excessive inflammation. Thus, to analyze the T‐cell response accurately, T‐cell markers that are detectable in the serum or plasma need to be discovered. The concentrations of IFN‐γ, IL‐4 and IL‐17 were all below detection limits, but that of IL‐21 was detectable in the plasma and inversely correlated with the production of IL‐21ex vivo. This may indicate the involvement of Th17 response in the pathogenesis of RA.