慢性咳嗽患者血清中IL-17、IL-33水平和FeNO浓度检测及其临床意义

doi:10.13481/j.1671-587x.20180124

摘要/Abstract

摘要： 目的：探讨慢性咳嗽患者血清中白细胞介素17（IL-17）、白细胞介素33（IL-33）水平与呼出气一氧化氮（FeNO）浓度的关系，进一步评估其在慢性咳嗽发病机制中的作用。方法：选择因慢性咳嗽8周以上就诊的160例患者作为慢性咳嗽组，同期在本院体检中心体检的60名健康者作为健康对照组。所有被选定研究对象均检测血清IL-17和IL-33水平，完成肺功能、FeNO浓度和综合过敏原检测。所有数据采用GraphPad Prism统计软件进行处理。比较2组研究对象血清中IL-17和IL-33水平，分析慢性咳嗽患者血清IL-17及IL-33水平与肺功能和FeNO浓度的相关性。结果：慢性咳嗽组患者血清中IL-17和IL-33水平均高于健康对照组（P<0.05）。慢性咳嗽组患者血清IL-17和IL-33水平均与患者第一秒用力呼气容积占预计值的百分比（FEV1%）呈负相关关系（r=-0.6245，r=-0.6722，均P<0.01），血清IL-33水平与FeNO浓度呈正相关关系（r_s=0.758，P<0.05），FeNO浓度越高，患者血清IL-33水平越高。慢性咳嗽患者血清中总IgE<100IU·mL^-1组患者FeNO浓度的几何均数（33ppb）明显低于总IgE>200IU·mL^-1组（78ppb）和总IgE100~200IU·mL^-1（69ppb）组（P<0.01）；后2组间比较差异无统计学意义（P=0.0824）。结论：血清IL-17和IL-33可能作为促炎因子参与慢性咳嗽的发病机制。血清IL-17和IL-33水平与慢性咳嗽患者肺通气功能改变呈负相关关系，血清IL-33升高可能预测嗜酸粒细胞性气道炎症并反映其严重程度。

关键词: 肺功能, 呼出气一氧化氮, 白细胞介素33, 慢性咳嗽, 白细胞介素17

Abstract: Objective: To investigate the relationships between the levels of serum interleukin-17(IL-17),interleukin-33(IL-33) and the concentration of fractional exhaled nitric oxide (FeNO) in the patients with chronic cough,and to further evaluate their effects in the pathogenesis of chronic cough. Methods: A total of 160 patients diagnosed with chronic cough for more than 8 weeks were chosenand used as chronic cough group.At the same time,60 healthy controlsreceived physical examination were selected as healthy control group.The levels of serum IL-17 and IL-33 of the subjects were examined and pulmonary function test,FeNO concentration test and comprehensive allergen test were performed.All data were analyzed by GraphPad Prism statistical software.The levels of serum IL-17 and IL-33 were compared between chronic cough group and healthy control groups.The correlations between the levels of serum IL-17 or IL-33 and lung function or FeNO in the patients with chronic cough were further analyzed. Results: The serum IL-17 and IL-33 levels of the patients in chronic cough groups were higher than those in healthy control group (P<0.05).The serum IL-17 and IL-33 levels in the patients with chronic cough showed a significant negative correlations with the percentage of the first second force expiratory volume to the estimated value(FEV1%) of the patients(r=-0.624 5,r=-0.672 2),and the level of serum IL-33 in the patients with chronic cough was positively correlated with the concentration of FeNO;the higher the concentration of FeNO,the higher the level of serum IL-33 (r_s=0.758,P<0.05).The FeNO concentration geometric mean of the patients with the serum total IgE<100 IU·mL^-1 (33 ppb) was significantly lower than those with the serum total IgE>200 IU·mL^-1 (78 ppb) and IgE 100-200 IU·mL^-1 (69 ppb) among the chronic cough patients (P<0.01),but there was no significant difference between the later two groups(P=0.082 4). Conclusion: The serum IL-17 and IL-33 may play an important role in the pathogenesis of chronic cough as proinflammatory factors.The levels of serum IL-17 or IL-33 have negative correlations with the pulmonary ventilation function in the patients with chronic cough.The increasing of serum IL-33 level may predict the formation of eosinophilic airway inflammation and reflect the severity of eosinophilic airway inflammation.

Key words: chronic cough, interleukin-17, fractional exhaled nitric oxide, interleukin-33, lung function

中图分类号:

R562

李星, 井弘宇, 陈立婷, 李丹, 钱东华. 慢性咳嗽患者血清中IL-17、IL-33水平和FeNO浓度检测及其临床意义[J]. 吉林大学学报(医学版), 2018, 44(01): 126-130.

LI Xing, JING Hongyu, CHEN Liting, LI Dan, QIAN Donghua. Detection of levels of serum interleukin-17,interleukin-33 and concentration of fractional exhaled nitric oxide in patients with chronic cough and its clinical significance[J]. Journal of Jilin University Medicine Edition, 2018, 44(01): 126-130.

参考文献

[1] 中华医学会呼吸病学分会哮喘学组.咳嗽的诊断与治疗指南(2015)[J].中华结核和呼吸杂志,2016,39(5):323-354.
[2] Lai K.Chinese National Guidelines on Diagnosis and Management of Cough:consensus and controversy[J].J Thorac Dis,2014,6(Suppl 7):S683-S688.
[3] Shen F,Gaffen SL.Structure-function relationships in the IL-17 receptor:implications for signal transduction and therapy[J].Cytokine,2008,41(2):92-104.
[4] McKinley L,Alcorn JF,Peterson A,et al.TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice[J].J Immunol,2008,181(6):4089-4097.
[5] Yang XO,Chang SH,Park H,et al.Regulation of inflammatory responses byIL-17F[J].J Exp Med,2008,205(5):1063-1075.
[6] Yagami A,Orihara K,Morita H,et al.IL-33 mediates inflammatory responses in human lung tissue cells[J].J Immunol,2010,185(10):5743-5750.
[7] Southcombe JH,Lédée N,Perrier d'Hauterive S,et al.Detection of soluble ST2 in human follicular fluid and luteinized granulosa cells[J].PLoS One,2013,8(9):74385.
[8] Lloyd CM.IL-33 family members and asthma-bridging innate and adaptive immune responses[J].Curr Opin Immunol,2010,22(6):800-806.
[9] Saenz SA,Taylor BC,Artis D.Welcome to the neighborhood:epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites[J].Immunol Rev,2008,226:172-190.
[10] Schmitz J,Owyang A,Oldham E,et al.IL-33,an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines[J].Immunity,2005,23(5):479-490.
[11] Komai-Koma M,Xu D,Li Y,et al.IL-33 is a chemoattractant for human Th2 cells[J].Eur J Immunol,2007,37(10):2779-2786.
[12] Schmitz J,Owyang A,Oldham E,et al.IL-33,an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines[J].Immunity,2005,23(5):479-490.
[13] Gour N,Wills-Karp M.IL-4 and IL-13 signaling in allergic airway disease[J].Cytokine,2015,75(1):68-78.
[14] Chung KF.Chronic' cough hypersensitivity syndrome':a more precise label for chronic cough[J].Pulm Pharmacol Ther,2011,24(3):267-271.
[15] Crespo A,Giner J,Torrejón M,et al.Clinical and inflammatory features of asthma with dissociation between fractional exhaled nitric oxide and eosinophils in induced sputum[J].J Asthma,2016,53(5):459-464.
[16] Neelamegan R,Saka V,Tamilarasu K,et al.Clinical utility of fractional exhaled nitric oxide (FeNO) as a biomarker to predict severity of disease and response to inhaled corticosteroid (ICS) in asthma patients[J].J Clin Diagn Res,2016,10(12):1-6.
[17] Asano T,Takemura M,Fukumitsu K,et al.Diagnostic utility of fractional exhaled nitric oxide in prolonged and chronic cough according to atopic status[J].Allergol Int,2017,66(2):344-350.
[18] 胡秋平,王玮,苏皎,等.阻塞性睡眠呼吸暂停低通气综合征伴高血压血清诱导型一氧化氮合成酶水平临床研究[J].中国实用内科杂志,2016,36(5):385-388.