Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma and COPD

被引:334
作者
Doe, Camille [1 ]
Bafadhel, Mona [1 ]
Siddiqui, Salman [1 ]
Desai, Dhananjay [1 ]
Mistry, Vijay [1 ]
Rugman, Paul [2 ]
McCormick, Margaret [2 ]
Woods, Joanne [3 ]
May, Richard [3 ]
Sleeman, Matthew A. [3 ]
Anderson, Ian K. [3 ]
Brightling, Christopher E. [1 ]
机构
[1] Univ Leicester, Inst Lung Hlth, Glenfield Hosp, Leicester LE3 9QP, Leics, England
[2] AstraZeneca Charnwood, Loughborough, Leics, England
[3] MedImmune Ltd, Cambridge, England
关键词
AIRWAY SMOOTH-MUSCLE; SPUTUM-EOSINOPHILIA; BRONCHIAL-MUCOSA; MESSENGER-RNA; INFLAMMATION; CELLS; MEDIATORS; RELEASE;
D O I
10.1378/chest.09-3058
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Asthma and COPD are characterized by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease. The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain. Methods: We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects. Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD. Results: The median (interquartile range) IL-17A cells/mm(2) submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P=.04). In COPD, IL-17A(+) cells/mm(2) submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P=.046). IL-17F(+) cells/mm(2) submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P=.001) but was not increased in subjects with COPD. IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P=.005). The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P<.0001) and was correlated with post-bronchodilator FEV1% predicted (r = -0.5, P=.008) and FEV1/FVC (r = -0.4, P=.04). Conclusions: Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation. CHEST 2010; 138(5):1140-1147
引用
收藏
页码:1140 / 1147
页数:8
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