title: IL-17A and the Promotion of Neutrophilia in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Department of Experimental Medical Science, Lund University, Lund, Sweden.|2 Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre.
authors.forename: Abraham B
authors.initials: AB
authors.lastname: Roos
authors.affiliation: 3 Pulmonary Medicine Division, Department of Veterans Affairs Western New York Healthcare System, University at Buffalo, State University of New York, Buffalo, New York; and.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.affiliation: 4 Medical Science Graduate Program, and.
authors.forename: Jake
authors.initials: J
authors.lastname: Nikota
authors.affiliation: 3 Pulmonary Medicine Division, Department of Veterans Affairs Western New York Healthcare System, University at Buffalo, State University of New York, Buffalo, New York; and.
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Wrona
authors.affiliation: 4 Medical Science Graduate Program, and.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dorrington
authors.affiliation: 1 Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sandén
authors.affiliation: 5 Hoffmann-La Roche, pRED, Pharma Research and Early Development, DTA Inflammation, Nutley, New Jersey.
authors.forename: Carla M T
authors.initials: CM
authors.lastname: Bauer
authors.affiliation: 3 Pulmonary Medicine Division, Department of Veterans Affairs Western New York Healthcare System, University at Buffalo, State University of New York, Buffalo, New York; and.
authors.forename: Pamela
authors.initials: P
authors.lastname: Shen
authors.affiliation: 2 Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre.
authors.forename: Dawn
authors.initials: D
authors.lastname: Bowdish
authors.affiliation: 5 Hoffmann-La Roche, pRED, Pharma Research and Early Development, DTA Inflammation, Nutley, New Jersey.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stevenson
authors.affiliation: 1 Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Jonas S
authors.initials: JS
authors.lastname: Erjefält
authors.affiliation: 2 Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre.|6 Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stampfli
mesh_terms: D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006192:Haemophilus Infections / Q000150:complications / Q000378:metabolism*; D006193:Haemophilus influenzae; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects
chemical_list: D020381:Interleukin-17
keywords: COPD; Haemophilus influenzae; IL-17A; disease exacerbation; neutrophil