IL-17A and the promotion of neutrophilia in acute exacerbation of chronic obstructive pulmonary disease

AB Roos, S Sethi, J Nikota, CT Wrona… - American journal of …, 2015 - atsjournals.org
AB Roos, S Sethi, J Nikota, CT Wrona, MG Dorrington, C Sandén, CMT Bauer, P Shen…
American journal of respiratory and critical care medicine, 2015atsjournals.org
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 …
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.
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