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他克莫司在强直性脊柱炎中的抗炎作用的初步研究:来自人体样本和小鼠模型的证据

A Pilot Study on the Anti-Inflammatory Effects of Tacrolimus in Ankylosing Spondylitis: Evidence from Human Samples and a Murine Model.

作者信息

Park Sooin, Kim Moon-Ju, Lee Yu Jeong, Yu Sung Min, Lee Hae-In, Jin So-Hee, Choi A-Ra, Shim Seung Cheol, Won Eun Jeong, Kim Tae-Jong

机构信息

Department of Rheumatology, Chonnam National University Medical School, Gwangju, Republic of Korea.

Department of Biomedical Sciences, Graduate School of Chonnam National University, Gwangju, Republic of Korea.

出版信息

Arch Rheumatol. 2025 Jun 23;40(2):189-196. doi: 10.5152/ArchRheumatol.2025.11154.

DOI:10.5152/ArchRheumatol.2025.11154
PMID:40757951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12260452/
Abstract

Background/Aims: This study aimed to evaluate the potential anti-inflammatory and therapeutic effects of tacrolimus in ankylosing spondylitis (AS). Materials and Methods: Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from AS patients were treated with tacrolimus and analyzed via flow cytometry to measure inflammatory cytokine-producing cells (IFN-γ, IL-17A, and GM-CSF). Additionally, cytokine levels (IFN-γ, IL-17A, TNF-α, and GM-CSF) in ex vivo cultured PBMC supernatants were quantified using enzyme-linked immunosorbent assay (ELISA). The in vivo effects of tacrolimus were assessed in an AS mouse model by evaluating clinical arthritis scores and analyzing inflammatory cytokine-producing cells (IFN-γ, IL-17A, and TNF-α) via flow cytometry. Results: Tacrolimus significantly suppressed the production of inflammatory cytokines (IFN-γ, IL-17A, and GM-CSF) in PBMCs and SFMCs from AS patients. Cytokine levels (IFN-γ, IL-17A, TNF-α, and GM-CSF) in ex vivo PBMC cultures were also markedly reduced with tacrolimus treatment. In the AS mouse model, tacrolimus treatment resulted in significantly lower clinical arthritis scores and reduced production of inflammatory cytokines (IFN-γ, IL-17A, and TNF-α). Conclusion: Tacrolimus demonstrates potential as a therapeutic agent for AS by suppressing inflammatory cytokine production in PBMCs and SFMCs from AS patients and exhibiting anti-inflammatory effects in an arthritis mouse model.

摘要

背景/目的:本研究旨在评估他克莫司在强直性脊柱炎(AS)中的潜在抗炎及治疗作用。材料与方法:用他克莫司处理AS患者的外周血单个核细胞(PBMC)和滑膜液单个核细胞(SFMC),并通过流式细胞术分析以检测产生炎性细胞因子的细胞(IFN-γ、IL-17A和GM-CSF)。此外,使用酶联免疫吸附测定(ELISA)对体外培养的PBMC上清液中的细胞因子水平(IFN-γ、IL-17A、TNF-α和GM-CSF)进行定量。通过评估临床关节炎评分并通过流式细胞术分析产生炎性细胞因子的细胞(IFN-γ、IL-17A和TNF-α),在AS小鼠模型中评估他克莫司的体内作用。结果:他克莫司显著抑制了AS患者PBMC和SFMC中炎性细胞因子(IFN-γ、IL-17A和GM-CSF)的产生。他克莫司处理后,体外PBMC培养物中的细胞因子水平(IFN-γ、IL-17A、TNF-α和GM-CSF)也明显降低。在AS小鼠模型中,他克莫司治疗导致临床关节炎评分显著降低,炎性细胞因子(IFN-γ、IL-17A和TNF-α)的产生减少。结论:他克莫司通过抑制AS患者PBMC和SFMC中炎性细胞因子的产生,并在关节炎小鼠模型中表现出抗炎作用,显示出作为AS治疗药物的潜力。

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本文引用的文献

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Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.近期抗风湿药物对类风湿关节炎相关淋巴增殖性疾病特征的影响。
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Updates on ankylosing spondylitis: pathogenesis and therapeutic agents.强直性脊柱炎的最新进展:发病机制与治疗药物
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CCL20 inhibition for treating inflammation in ankylosing spondylitis.CCL20 抑制治疗强直性脊柱炎炎症。
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