4.7 Article

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

Journal

CHEST
Volume 138, Issue 5, Pages 1140-1147

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1378/chest.09-3058

Keywords

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Funding

  1. Asthma UK
  2. MedImmune Ltd
  3. Wellcome Senior Clinical Fellowship
  4. MedImmune
  5. AstraZeneca
  6. GlaxoSmithKline
  7. Roche
  8. Genentech Inc
  9. Asthma UK [05/058] Funding Source: researchfish
  10. National Institute for Health Research [CL-2008-11-005] Funding Source: researchfish

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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

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