支气管哮喘患者外周血Th17/Treg及相关细胞因子的表达及临床意义
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摘要
目的探讨支气管哮喘患者外周血辅助性T细胞17(Th17)/调节性T细胞(Treg)及相关细胞因子的表达情况及临床意义。方法收集2016年10月～2017年10月我院收治的84例急性发作的支气管哮喘患者作为哮喘组,另选取50例健康体检者作为对照组。采用流式细胞术检测外周血Th17细胞、Treg细胞水平,酶联免疫吸附试验(ELISA)检测血白细胞介素17(IL-17)、白细胞介素10(IL-10)、转化生长因子β1(TGF-β1)表达水平,并测量肺功能指标。分析患者各指标与肺功能指标的相关性。结果哮喘组急性期的外周血Th17细胞、Th17/Treg、血浆IL-17水平高于对照组及缓解期,哮喘组缓解期以上各指标高于对照组,差异均有统计学意义(P<0.05)。哮喘组急性期的IL-10、TGF-β1、Treg细胞以及肺功能指标低于对照组及缓解期,而缓解期的IL-10、TGF-β1、Treg细胞低于对照组,差异均有统计学意义(P<0.05);哮喘组患者急性期的外周血Th17细胞、血浆IL-17水平与肺功能指标均成负相关(P<0.05);而Treg细胞、IL-10、TGF-β1与肺功能指标均成正相关(P<0.05)。结论支气管哮喘患者体内存在外周血Th17/Treg平衡紊乱,其效应细胞因子分泌出现异常。外周血Th17/Treg变化可反应哮喘患者体内炎症水平,有助于对哮喘机制进行进一步研究,为临床诊疗提供新策略。
Objective To investigate the expression and clinical significance of helper T cell 17(Th17)/regulatory T cell(Treg) and related cytokines in peripheral blood of patients with bronchial asthma. Methods A total of 84 patients with acute bronchial asthma admitted in our hospital from October 2016 to October 2017 were enrolled as asthma group. Another 50 healthy people were selected as control group at the same time. The levels of Th17 cells and Treg cells were detected by flow cytometry, the expression levels of serum interleukin-17(IL-17), interleukin-10(IL-10) and transforming growth factor-β1(TGF-β1) were detected by enzyme-linked immunosorbent assay(ELISA), and pulmonary function index was also measured. The correlations between levels of Th17 cells, Treg cells, IL-17, IL-10, TGF-β1 and pulmonary function index in patients with bronchial asthma were analyzed. Results The levels of Th17 cells, Th17/Treg and IL-17 in asthma group in acute stage were statistically higher than those in remission stage and control group, and the above indexes in the remission stage were higher than those in the control group(P<0.05). The levels of IL-10,TGF-β1, Treg and the indexes pulmonary function in asthma group in acute stage were statistically lower than those in control group and remission stage, and those in the asthma group in remission stage were lower than those in the control group(P <0.05). The levels of Th17 cells and IL-17 were negatively correlated with pulmonary function in asthma group in acute stage, and Treg cells, IL-10 and TGF-β1 were positively correlated with lung function indexes(P<0.05). Conclusion There is a balance disorder of Th17/Treg in peripheral blood in patients with bronchial asthma,and the secretion of related cytokines is abnormal. The change of Th17/Treg in peripheral blood can reflect the level of inflammation in patients with bronchial asthma, which is helpful to further study the mechanism of asthma and provide a new strategy for clinical diagnosis and treatment.
Objective To investigate the expression and clinical significance of helper T cell 17(Th17)/regulatory T cell(Treg) and related cytokines in peripheral blood of patients with bronchial asthma. Methods A total of 84 patients with acute bronchial asthma admitted in our hospital from October 2016 to October 2017 were enrolled as asthma group. Another 50 healthy people were selected as control group at the same time. The levels of Th17 cells and Treg cells were detected by flow cytometry, the expression levels of serum interleukin-17(IL-17), interleukin-10(IL-10) and transforming growth factor-β1(TGF-β1) were detected by enzyme-linked immunosorbent assay(ELISA), and pulmonary function index was also measured. The correlations between levels of Th17 cells, Treg cells, IL-17, IL-10, TGF-β1 and pulmonary function index in patients with bronchial asthma were analyzed. Results The levels of Th17 cells, Th17/Treg and IL-17 in asthma group in acute stage were statistically higher than those in remission stage and control group, and the above indexes in the remission stage were higher than those in the control group(P<0.05). The levels of IL-10,TGF-β1, Treg and the indexes pulmonary function in asthma group in acute stage were statistically lower than those in control group and remission stage, and those in the asthma group in remission stage were lower than those in the control group(P <0.05). The levels of Th17 cells and IL-17 were negatively correlated with pulmonary function in asthma group in acute stage, and Treg cells, IL-10 and TGF-β1 were positively correlated with lung function indexes(P<0.05). Conclusion There is a balance disorder of Th17/Treg in peripheral blood in patients with bronchial asthma,and the secretion of related cytokines is abnormal. The change of Th17/Treg in peripheral blood can reflect the level of inflammation in patients with bronchial asthma, which is helpful to further study the mechanism of asthma and provide a new strategy for clinical diagnosis and treatment.
引文
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[2]Hou X,Wan H,Ai X,et al.Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma[J].Clin Respir J,2016,10(3):371-379.
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[4]种靖慧,解金辉.Th17细胞及其分泌的IL-17在自身免疫性疾病中的作用[J].继续医学教育,2018,32(7):129-131.
[5]孙德彬,熊雪芳,周家峰,等.哮喘患者外周血调节性T细胞和Th1/Th2的变化及其与哮喘病情的关系[J].中国现代医生,2016,54(16):6-9.
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[8]史凤磊,苏秋菊,潘春梅.穴位敷贴联合加味小青龙汤对支气管哮喘急性发作期患者气道重塑及炎性细胞因子水平的影响[J].国际中医中药杂志,2018,40(3):218-221.
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[10]Chen J,Wang W,Li Q.Increased Th1/Th17 responses contribute to low-grade inflammation in age-related macular degeneration[J].Cell Physiol Biochem,2017,44(1):357-367.
[11]尹秀志,曲书强.IL-17在哮喘中的研究进展[J].临床肺科杂志,2016,21(1):155-159.
[12]陈美元,徐红,周瑶,等.IL-17在哮喘小鼠模型中表达及其对肥大细胞IL-6分泌的影响[J].南京医科大学学报(自然科学版),2015,35(3):363-366.
[13]刘娟,李敏.CD4+CD25+调节性T细胞与支气管哮喘的研究进展[J].大家健康(学术版),2016,10(4):12,14.
[14]Rothstein DM,Camirand G.New insights into the mechanisms of Treg function[J].Curr Opin Organ Transplant,2015,20(4):376-384.
[15]Li X,Zheng Y.Regulatory T cell identity:formation and maintenance[J].Trends Immunol,2015,36(6):344-353.
[16]Cecchi L,D′Amato G,Annesi-Maesano I,et al.外暴露组与呼吸道、皮肤过敏性疾病[J].中华临床免疫和变态反应杂志,2018,12(5):555-564.
[17]杜璐玲,陈建永,郑淑梅.吸入布地奈德联合细菌溶解产物对成人支气管哮喘患者炎症因子基质金属蛋白酶-9金属蛋白酶抑制酶-1水平及气道重塑的影响[J].山西医药杂志,2016,45(21):2526-2528.
[18]Park GM,Han HW,Kim JY,et al.Association of symptom control with changes in lung function,bronchial hyperresponsiveness,and exhaled nitric oxide after inhaled corticosteroid treatment in children with asthma[J].Allergol Int,2016,65(4):439-443.
[2]Hou X,Wan H,Ai X,et al.Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma[J].Clin Respir J,2016,10(3):371-379.
[3]Farahani P,Halabian R,Vahedi E,et al.Increased genes expression levels of cytokines related to Th17/Treg cells in peripheral blood mononuclear cell correlate with clinical severity in COPD and mustard gas-exposed patients[J].Iran J Allergy Asthma Immunol,2017,16(5):396-403.
[4]种靖慧,解金辉.Th17细胞及其分泌的IL-17在自身免疫性疾病中的作用[J].继续医学教育,2018,32(7):129-131.
[5]孙德彬,熊雪芳,周家峰,等.哮喘患者外周血调节性T细胞和Th1/Th2的变化及其与哮喘病情的关系[J].中国现代医生,2016,54(16):6-9.
[6]中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南(支气管哮喘的定义、诊断、治疗及教育和管理方案)[J].中华内科杂志,2003,42(11):817-822.
[7]赵彩霞.支气管哮喘发病机制的研究进展[J].医学理论与实践,2016,29(7):870-872.
[8]史凤磊,苏秋菊,潘春梅.穴位敷贴联合加味小青龙汤对支气管哮喘急性发作期患者气道重塑及炎性细胞因子水平的影响[J].国际中医中药杂志,2018,40(3):218-221.
[9]Rogala B,Bozek A,Gluck J,et al.Prevalence of IgE-mediated allergy and evaluation of Th1/Th2 cytokine profiles in patients with severe bronchial asthma[J].Postepy Dermatol Alergol,2015,32(4):274-280.
[10]Chen J,Wang W,Li Q.Increased Th1/Th17 responses contribute to low-grade inflammation in age-related macular degeneration[J].Cell Physiol Biochem,2017,44(1):357-367.
[11]尹秀志,曲书强.IL-17在哮喘中的研究进展[J].临床肺科杂志,2016,21(1):155-159.
[12]陈美元,徐红,周瑶,等.IL-17在哮喘小鼠模型中表达及其对肥大细胞IL-6分泌的影响[J].南京医科大学学报(自然科学版),2015,35(3):363-366.
[13]刘娟,李敏.CD4+CD25+调节性T细胞与支气管哮喘的研究进展[J].大家健康(学术版),2016,10(4):12,14.
[14]Rothstein DM,Camirand G.New insights into the mechanisms of Treg function[J].Curr Opin Organ Transplant,2015,20(4):376-384.
[15]Li X,Zheng Y.Regulatory T cell identity:formation and maintenance[J].Trends Immunol,2015,36(6):344-353.
[16]Cecchi L,D′Amato G,Annesi-Maesano I,et al.外暴露组与呼吸道、皮肤过敏性疾病[J].中华临床免疫和变态反应杂志,2018,12(5):555-564.
[17]杜璐玲,陈建永,郑淑梅.吸入布地奈德联合细菌溶解产物对成人支气管哮喘患者炎症因子基质金属蛋白酶-9金属蛋白酶抑制酶-1水平及气道重塑的影响[J].山西医药杂志,2016,45(21):2526-2528.
[18]Park GM,Han HW,Kim JY,et al.Association of symptom control with changes in lung function,bronchial hyperresponsiveness,and exhaled nitric oxide after inhaled corticosteroid treatment in children with asthma[J].Allergol Int,2016,65(4):439-443.