IL-17A and the Promotion of Neutrophilia in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
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.
['Roos|Abraham B|AB|', 'Sethi|Sanjay|S|', 'Nikota|Jake|J|', 'Wrona|Catherine T|CT|', 'Dorrington|Michael G|MG|', 'Sandén|Caroline|C|', 'Bauer|Carla M T|CM|', 'Shen|Pamela|P|', 'Bowdish|Dawn|D|', 'Stevenson|Christopher S|CS|', 'Erjefält|Jonas S|JS|', 'Stampfli|Martin R|MR|']
D000368:Aged D000818:Animals D004195:Disease Models, Animal D005260:Female D006192:Haemophilus Infections D006193:Haemophilus influenzae D006801:Humans D020381:Interleukin-17 D007958:Leukocyte Count D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008875:Middle Aged D020556:Neutrophil Infiltration D009504:Neutrophils D029424:Pulmonary Disease, Chronic Obstructive D012907:Smoking
IL-17A Haemophilus influenzae neutrophil COPD disease exacerbation