Relationship between the anti-inflammatory properties of salmeterol/fluticasone and the expression of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in COPD.

Relationship between the anti-inflammatory properties of salmeterol/fluticasone and the expression of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in COPD.
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DOI:
10.1186/1465-9921-12-142
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发表时间:
2011-10-28
影响因子:
5.8
通讯作者:
Wang CZ
Wang CZ
中科院分区:
医学2区
文献类型:
--
作者:
Yang L;Ma QL;Yao W;Zhang Q;Chen HP;Wang GS;Wang CZ

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沙美特罗联合氟替卡松(SFC)对慢性阻塞性肺疾病(COPD)患者具有抗炎和改善临床症状的作用。然而,SFC的抗炎机制尚不清楚。在本研究中,我们研究了SFC治疗后COPD的炎症反应,以及炎症因子与CD4+CD25+Foxp3+调节性T细胞(Foxp3+Tregs)水平的关系。21例中重度COPD患者接受50/500 μg SFC治疗,每天2次,连续12周。治疗前后,采用改良医学研究委员会(MMRC)呼吸困难量表和6分钟步行测试对患者进行评估。计数诱导痰中中性粒细胞、单核细胞和淋巴细胞的数量。ELISA法检测大鼠痰上清及外周血中炎症前IL-8、TNF-α、IL-17A、细胞因子IL-10水平。流式细胞术检测Foxp3+Tregs在外周血总CD4+ T细胞中的比例。统计学分析IL-17A水平与Foxp3+Tregs百分比的关系。经SFC治疗后,COPD患者1 s用力呼气量占预测值的百分比(FEV1%)和6 min步行距离显著增加,呼吸困难评分下降。诱导痰中细胞总数、中性粒细胞和中性粒细胞百分比均显著降低,单核细胞比例显著升高。痰上清及血中炎性因子IL-8、TNF-α、IL-17A水平明显降低,IL-10水平不变。Foxp3+Tregs在外周血总CD4+T细胞群中的比例明显高于治疗前。IL-17A水平与Foxp3+Tregs在CD4+T细胞中的比例呈负相关。SFC可以降低炎症因子水平,改善慢性阻塞性肺病的症状。炎症因子水平与COPD中Foxp3+Tregs的变化有关。本研究已在http://www.chictr.org(中国临床试验注册)注册,注册号如下:ChiCTR-TNC-10001270
Salmeterol and fluticasone combination (SFC) has anti-inflammatory effects and improves clinical symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the anti-inflammatory mechanism of SFC remains unclear. In this study, we investigated the inflammatory responses of COPD, as well as the relationship of the inflammatory factors with the levels of CD4+CD25+Foxp3+ regulatory T cells (Foxp3+Tregs) after SFC therapy. Twenty-one patients with moderate or severe COPD received treatment with 50/500 μg of SFC twice a day for 12 weeks. Before and after treatment, the patients were evaluated using the Modified Medical Research Council (MMRC) dyspnea scale and by conducting a 6-min walk test. The number of neutrophils, monocytes and lymphocytes in induced sputum were counted. Levels of cytokines, including pre-inflammatory IL-8, TNF-α, IL-17A and cytokine IL-10, in the sputum supernatant and peripheral blood were measured by ELISA. The proportion of Foxp3+Tregs in the total CD4+ T cell of the peripheral blood was determined by flow cytometry. The relationship between IL-17A levels and the percentage of Foxp3+Tregs was analyzed by statistical analysis. After treatment with SFC, the forced expiratory volume in 1 s as a percentage of predicted values (FEV1%) and the 6-min walk distance in the COPD patients significantly increased, while dyspnea scores decreased. The total number of cells, neutrophils, and the percentage of neutrophils in induced sputum reduced notably, while the proportion of monocytes was significantly increased. Levels of the inflammatory cytokines IL-8, TNF-α, and IL-17A in the sputum supernatant and in the blood were markedly lowered, while IL-10 levels were unchanged. The proportion of Foxp3+Tregs in the total CD4+T cell population in the peripheral blood was drastically higher than that before treatment. The level of IL-17A was negatively correlated with the proportion of Foxp3+Tregs in CD4+T cells. SFC can reduce the levels of inflammatory factors and improve symptoms of COPD. The levels of inflammatory factors are associated with the variation of Foxp3+Tregs in COPD. This study was registered with http://www.chictr.org (Chinese Clinical Trial Register) as follows: ChiCTR-TNC-10001270
调节性T细胞在类风湿关节炎和抗TNFALPHA治疗中的逆转功能受损。
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