中国医学科学院学报

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中国医学科学院学报

中国医学科学院学报 ›› 2020, Vol. 42 ›› Issue (5): 596-602.doi: 10.3881/j.issn.1000-503X.11711

• 论著 • 上一篇    下一篇

吡非尼酮可抑制肺泡巨噬细胞中细胞因子/趋化因子释放

龙小平1,唐艳华1,李建民2,王卫忠1,欧大明3,许丽慧1,何菁子1,谢立虎3()   

  1. 1 南华大学附属第一医院呼吸与危重症医学科,湖南衡阳 421001
    2 湖南省人民医院呼吸重症医学科,长沙 410005
    3 南华大学附属第一医院风湿免疫科,湖南衡阳 421001
  • 收稿日期:2019-07-01 出版日期:2020-10-30 发布日期:2020-11-02
  • 通讯作者: 谢立虎 E-mail:xilihu1983@qq.com
  • 基金资助:
    湖南省自然科学基金青年基金(2018JJ3470)

Pirfenidone Inhibits Cytokines/chemokines Release from Alveolar Macrophages

LONG Xiaoping1,TANG Yanhua1,LI Jianmin2,WANG Weizhong1,OU Daming3,XU Lihui1,HE Jingzi1,XIE Lihu3()   

  1. 1 Department of Pulmonary and Critical Care Medicine,the First Affiliated Hospital of University of South China, Hengyang,Hunan 421001,China
    2 Respiratory and Intensive Care Unit,Hunan Provincial People’s Hospital,Changsha 410005,China
    3 Department of Rheumatology and Immunology,the First Affiliated Hospital of University of South China, Hengyang,Hunan 421001,China
  • Received:2019-07-01 Online:2020-10-30 Published:2020-11-02
  • Contact: XIE Lihu E-mail:xilihu1983@qq.com
  • Supported by:
    Hunan Natural Science Foundation Youth Fund(2018JJ3470)

摘要:

目的 评估吡非尼酮对特发性非特异性间质性肺炎(iNSIP)和特发性肺纤维化(IPF)患者肺泡巨噬细胞(AMs)细胞因子/趋化因子的影响。方法 以2015年1月至2018年12月在南华大学附属第一医院确诊的10例iNSIP患者和11例IPF患者为研究对象,同期具有正常肺泡灌洗液(BALF)细胞分类且没有任何间质性肺疾病的8例患者为对照。取所有患者BALF的AMs在有和没有脂多糖(LPS)刺激的条件下进行培养,分别以0、0.03、0.10、0.30 mg/ml吡非尼酮处理,采用基于荧光珠的多重技术Luminex检测培养上清液中Th1型细胞因子[肿瘤坏死因子(TNF-α)、可溶性肿瘤坏死因子受体-1(sTNFR)-1、sTNFR-2、白细胞介素-1(IL)-1β]、Th2型细胞因子[IL-10、单核-巨噬细胞集落刺激因子(GM-CSF)]、促血管形成趋化因子[IL-18、巨噬细胞炎性蛋白-1β(MIP-1β)]和抗血管形成趋化因子[重组人干扰素-γ诱导单核细胞因子(MIG)、干扰素诱导蛋白-10(IP-10)]水平。结果 iNSIP和IPF组患者的AMs在自发(基础状态下)和LPS刺激下释放的TNF-α、sTNFR-1、sTNFR-2、IL-1β、IL-10、MIP-1β、MIG和IP-10水平均显著高于对照组(P均<0.05),3组间IL-18水平在自发状态下差异无统计学意义(P>0.05),iNSIP和IPF组患者IL-18水平在LPS刺激下均显著低于对照组(P均<0.05);iNSIP组患者AMs产生的MIG和IP-10浓度在自发和LPS刺激下均显著高于IPF组(P均<0.05)。吡非尼酮在浓度为0.10和0.30 mg/ml时均可显著抑制iNSIP和IPF患者AMs释放上述所有细胞因子/趋化因子,两组间差异无统计学意义(P均>0.05)。结论 iNSIP组患者AMs产生的MIG和IP-10水平高于IPF患者。0.10和0.30 mg/ml吡非尼酮可显著抑制对iNSIP组和IPF组患者AMs释放的细胞因子/趋化因子,但对两者无明显差异。

关键词: 吡非尼酮, 细胞因子/趋化因子, 肺泡巨噬细胞, 特发性肺纤维化, 特发性非特异性间质性肺炎

Abstract:

Objective To investigate the effect of pirfenidone on cytokine/chemokine production by alveolar macrophages(AMs)in patients with idiopathic nonspecific interstitial pneumonia(iNSIP)or idiopathic pulmonary fibrosis(IPF).Methods We prospectively enrolled 10 iNSIP patients,11 IPF patients,and 8 non-interstitial lung disease(non-ILD)patients(control group)from our center from January 2015 to December 2018.AMs from bronchoalveolar lavage fluid(BALF)were cultured with or without lipopolysaccharide(LPS)stimulation.The production of Th1 cytokines [soluble tumor necrosis factor receptor(sTNFR)-1,sTNFR-2,and interleukin(IL)-1β],Th2 cytokines [IL-10 and granulocyte-macrophage colony-stimulating factor(GM-CSF)],angiogenic chemokines [IL-18 and macrophage inflammatory protein(MIP)-1β],and angiostatic chemokines [interferon-gama inducible monokines(MIG)and interferon-gama inducible protein(IP-10)] in the culture supernatants were measured by a bead-based assay,Luminex.The effect of pirfenidone on the cytokine/chemokine production was tested at various concentrations(0,0.03,0.10,0.30 mg/ml).Results The spontaneous and LPS-stimulated release of TNF-α,sTNFR-1,sTNFR-2,IL-1β,IL-10,MIP-1β,MIG,and IP-10 by AMs were significantly increased in iNSIP and IPF groups compared with control group(all P<0.05),but no difference in IL-18 was seen among three groups(all P>0.05).MIG and IP-10 were significantly higher in iNSIP group than in IPF group(both P<0.05).Pirfenidone suppressed the spontaneous and LPS-stimulated AMs release of all studied cytokine/chemokine in iNSIP and IPF in a dose-dependent manner at concentrations of 0.10 and 0.30 mg/ml,and no difference was observed between iNSIP and IPF groups(both P>0.05).Conclusion Pirfenidone can markedly suppress cytokine/chemokine expression in iNSIP and IPF patients,but the difference is not significant between these two groups of patients.

Key words: pirfenidone, cytokine/chemokine, alveolar macrophages, idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia

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