IL-17A and the Promotion of Neutrophilia in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Am J Respir Crit Care Med. 2015 Aug 15;192(4):428-37. doi: 10.1164/rccm.201409-1689OC.


Rationale: Nontypeable Haemophilus influenzae (NTHi) causes acute exacerbation of chronic obstructive pulmonary disease (AECOPD). IL-17A is central for neutrophilic inflammation and has been linked to COPD pathogenesis.

Objectives: We investigated whether IL-17A is elevated in NTHi-associated AECOPD and required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke.

Methods: Experimental studies with cigarette smoke and NTHi infection were pursued in gene-targeted mice and using antibody intervention. IL-17A was measured in sputum collected from patients with COPD at baseline, during, and after AECOPD.

Measurements and main results: Exacerbated airway neutrophilia in cigarette smoke-exposed mice infected with NTHi was associated with an induction of IL-17A. In agreement, elevated IL-17A was observed in sputum collected during NTHi-associated AECOPD, compared with samples collected before or after the event. NTHi-exacerbated neutrophilia and induction of neutrophil chemoattractants over the background of cigarette smoke, as observed in wild-type mice, was absent in Il17a(-/-) mice and in mice treated with a neutralizing anti-IL-17A antibody. Further studies revealed that IL-1 receptor (R)1 signaling was required for IL-17A-dependent neutrophilia. Moreover, deficiency or therapeutic neutralization of IL-17A did not increase bacterial burden or delay bacterial clearance.

Conclusions: IL-17A is induced during NTHi-associated AECOPD. Functionally, IL-1R1-dependent IL-17A is required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke. Targeting IL-17A in AECOPD may thus be beneficial to reduce neutrophil recruitment to the airways.

Keywords: COPD; Haemophilus influenzae; IL-17A; disease exacerbation; neutrophil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Disease Models, Animal
  • Female
  • Haemophilus Infections / complications
  • Haemophilus Infections / metabolism*
  • Haemophilus influenzae*
  • Humans
  • Interleukin-17 / metabolism*
  • Leukocyte Count
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neutrophil Infiltration
  • Neutrophils / physiology*
  • Pulmonary Disease, Chronic Obstructive / complications*
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Smoking / adverse effects


  • Interleukin-17