Noack Mélissa, Ndongo-Thiam Ndiémé, Miossec Pierre
Immunogenomics and Inflammation Research Unit, EA 4130, Edouard Herriot Hospital, Hospices Civils de Lyon and University Claude Bernard Lyon 1 , Lyon , France.
Front Immunol. 2016 Nov 17;7:509. doi: 10.3389/fimmu.2016.00509. eCollection 2016.
During rheumatoid arthritis (RA), steroids and biotherapies are used alone and combined. Efficacy has been established in clinical trials but their differential effects at the cellular level are less documented. The aim was to study these cellular effects using an model with synoviocytes interacting with peripheral blood mononuclear cells (PBMC) to reproduce the interactions in the RA synovium.
Activated-PBMC were cocultured with RA synoviocytes during 48 h. A dose-response of methylprednisolone (MP) was tested and different biotherapies (Infliximab, Etanercept, Adalimumab, Tocilizumab, Abatacept, and Rituximab) were added alone or in combination with MP. Cytokine production (IL-17, IL-6, IL-1β, IFN-γ and IL-10) was measured by ELISA.
Addition of MP to cocultures inhibited the production of all cytokines. The response to the biotherapies alone was treatment-dependent. IL-17 production was inhibited only by Tocilizumab ( = 0.004), while IL-6 was decreased only by Infliximab ( ≤ 0.002). IL-1β level was affected in all conditions ( ≤ 0.03). IFN-γ production was mainly decreased by Infliximab ( = 0.004) and IL-10 by Infliximab and Tocilizumab ( ≤ 0.004). The combination MP and biotherapies did not induce an additional effect on pro-inflammatory cytokine inhibition. The combination MP and biotherapies induced a higher IL-10 secretion than MP alone, mainly with Rituximab.
Steroids inhibited the secretion of all cytokines, and low doses were as potent. The anti-inflammatory effect of biotherapies was dependent on their mechanism of action. MP and biotherapy combination did not enhance the inhibitory effect on pro-inflammatory cytokines but could have a beneficial effect by increasing IL-10 production.
在类风湿关节炎（RA）中，类固醇和生物疗法可单独使用或联合使用。其疗效已在临床试验中得到证实，但它们在细胞水平上的差异作用记录较少。目的是使用滑膜细胞与外周血单核细胞（PBMC）相互作用的模型来研究这些细胞效应，以重现RA滑膜中的相互作用。
活化的PBMC与RA滑膜细胞共培养48小时。测试了甲泼尼龙（MP）的剂量反应，并单独添加或与MP联合添加不同的生物疗法（英夫利昔单抗、依那西普、阿达木单抗、托珠单抗、阿巴西普和利妥昔单抗）。通过酶联免疫吸附测定法（ELISA）测量细胞因子的产生（IL-17、IL-6、IL-1β、IFN-γ和IL-10）。
向共培养物中添加MP可抑制所有细胞因子的产生。单独使用生物疗法的反应取决于治疗方法。仅托珠单抗可抑制IL-17的产生（P = 0.004），而仅英夫利昔单抗可降低IL-6（P≤0.002）。在所有情况下IL-1β水平均受到影响（P≤0.03）。IFN-γ的产生主要被英夫利昔单抗降低（P = 0.004），而IL-10则被英夫利昔单抗和托珠单抗降低（P≤0.004）。MP与生物疗法的联合使用并未对促炎细胞因子的抑制产生额外影响。MP与生物疗法的联合使用比单独使用MP诱导更高的IL-10分泌，主要是与利妥昔单抗联合时。
类固醇抑制所有细胞因子的分泌，低剂量同样有效。生物疗法的抗炎作用取决于其作用机制。MP与生物疗法的联合使用并未增强对促炎细胞因子的抑制作用，但可通过增加IL-10的产生产生有益效果。
