IL-17A is specifically elevated in NTHi-associated AECOPD and end-stage COPD

Abstract

Introduction: IL-17A is associated to chronic obstructive pulmonary disease (COPD). The expression and role of IL-17A in acute exacerbation of COPD (AECOPD) and end-stage disease is, however, unknown. Aim: Characterize the expression and functional role of IL-17A in AECOPD, and relevance to disease progression. Methods: IL-17A was measured in sputum before, during and after nontypable Haemophilus influenzae (NTHi)-associated, culture positive and culture negative AECOPD, and in lung tissue specimens from GOLD I-IV COPD patients and asymptomatic smokers/never smokers. Cigarette smoke exposure of gene-targeted mice was used in conjunction with NTHi infection to establish the functional relevance of IL-17A. Results: IL-17A was elevated in sputum during NTHi-associated AECOPD, compared to before or after the event, but not during culture negative AECOPD, or AECOPD associated with bacteria other than NTHi. IL-17A was, however, increased in a pooled analysis of all AECOPD. Functionally, IL-1 receptor 1 dependent IL-17A was required for NTHi-exacerbated neutrophilia in cigarette smoke-exposed mice. Alveolar macrophages were identified as a potential source of IL-17A. Lastly, lung tissue expression of IL-17A was significantly increased in end-stage COPD compared to asymptomatic smokers. Conclusion: IL-17A is specifically increased during NTHi-associated AECOPD and in end-stage disease. Functionally, IL-17A is required for NTHi-exacerbated inflammation over the background of cigarette smoke. As AECOPD accelerates COPD, IL-17A may participate in driving the progression of COPD by promoting neutrophil accumulation in lung tissue.