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An investigation into the modulation of T cell phenotypes by amitriptyline and nortriptyline
European Neuropsychopharmacology ( IF 5.6 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.euroneuro.2019.12.106
Jonathan Royds 1 , Melissa J Conroy 2 , Margaret R Dunne 2 , Connail McCrory 1 , Joanne Lysaght 2
Affiliation  

Amitriptyline is prescribed for treating the symptoms of neuroinflammatory disorders including neuropathic pain and fibromyalgia. As amitriptyline has evidence of modulating the neuroimmune interface; the effects of amitriptyline treatment on T-cell phenotype and function were examined in vitro. Peripheral blood mononuclear cells(PBMCs) were isolated and treated with amitriptyline, nortriptyline and a combination of both drugs. Toxicity for T-cells was assessed by Annexin V/Propidium Iodide staining. Activation status and cytokine expression by T-cells post treatment was assessed by flow cytometry. The levels of secreted cytokines, chemokines and neurotrophins were measured by ELISA in the supernatants. There was no significant increase in T-cell death following 24 or 48 h compared to controls. There were significantly lower frequencies of CD8+ T-cells after treatment with amitriptyline, nortriptyline and a combination of both compared to a Vehicle Control(VC)(p<0.001). The frequencies of naive CD8+CD45RA+ cells were significantly lower after amitriptyline, nortriptyline and a combination of both (p<0001). The frequencies of CD27+CD4+(p<0.05) and CD27+CD8+(p<0.01) T-cells were also significantly lower following combination drug treatment. Significantly lower frequencies of IFN-γ-producing CD8+ T-cells were observed with all treatment combinations(p<0.05) and frequencies of IL-17-producing CD4+ and CD8+ T-cells were significantly lower following amitriptyline treatment (p<0.05). Frequencies of Natural Killer T-cells were significantly higher following treatment with nortriptyline (p<0.05). Significantly higher levels of IL-16 (p<0.001) and lower levels of TNF-β (p<0.05) were observed in supernatants. This data indicates that both amitriptyline and nortriptyline modulate the phenotype and function of T-cells and this may have clinical relevance in the pathologies of its off-label applications.

中文翻译:

阿米替林和去甲替林对 T 细胞表型调节的研究

阿米替林用于治疗神经炎性疾病的症状,包括神经性疼痛和纤维肌痛。由于阿米替林具有调节神经免疫界面的证据;在体外检查了阿米替林治疗对 T 细胞表型和功能的影响。外周血单个核细胞(PBMC)被分离并用阿米替林、去甲替林和两种药物的组合处理。通过膜联蛋白 V/碘化丙啶染色评估 T 细胞的毒性。通过流式细胞术评估处理后 T 细胞的活化状态和细胞因子表达。通过ELISA测量上清液中分泌的细胞因子、趋化因子和神经营养因子的水平。与对照组相比,24 或 48 小时后 T 细胞死亡没有显着增加。与载体对照 (VC) 相比,用阿米替林、去甲替林和两者的组合治疗后 CD8+ T 细胞的频率显着降低(p<0.001)。在使用阿米替林、去甲替林和两者的组合后,幼稚 CD8+CD45RA+ 细胞的频率显着降低(p<0001)。联合药物治疗后,CD27+CD4+(p<0.05) 和 CD27+CD8+(p<0.01) T 细胞的频率也显着降低。在所有治疗组合中观察到产生 IFN-γ 的 CD8+ T 细胞的频率显着降低(p<0.05),并且在阿米替林治疗后产生 IL-17 的 CD4+ 和 CD8+ T 细胞的频率显着降低(p<0.05)。用去甲替林治疗后,自然杀伤 T 细胞的频率显着升高(p<0.05)。在上清液中观察到显着更高水平的 IL-16 (p<0.001) 和更低水平的 TNF-β (p<0.05)。该数据表明阿米替林和去甲替林均可调节 T 细胞的表型和功能,这可能与其标签外应用的病理具有临床相关性。
更新日期:2020-02-01
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