RT Journal Article
SR Electronic
T1 Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2301966
DO 10.1183/13993003.01966-2023
VO 64
IS 2
A1 Perea, Lidia
A1 Bottier, Mathieu
A1 Cant, Erin
A1 Richardson, Hollian
A1 Dicker, Alison J.
A1 Shuttleworth, Morven
A1 Giam, Yan Hui
A1 Abo-Leyah, Hani
A1 Finch, Simon
A1 Huang, Jeffrey T-J.
A1 Shteinberg, Michal
A1 Goeminne, Pieter C.
A1 Polverino, Eva
A1 Altenburg, Josje
A1 Blasi, Francesco
A1 Welte, Tobias
A1 Aliberti, Stefano
A1 Sibila, Oriol
A1 Chalmers, James D.
A1 Shoemark, Amelia
YR 2024
UL http://erj.ersjournals.com/content/64/2/2301966.abstract
AB Rationale The inflammasome is a key regulatory complex of the inflammatory response leading to interleukin-1β (IL-1β) release and activation. IL-1β amplifies inflammatory responses and induces mucus secretion and hyperconcentration in other diseases. The role of IL-1β in bronchiectasis has not been investigated.Objectives To characterise the role of airway IL-1β in bronchiectasis, including the association with mucus properties, ciliary function, airway inflammation, microbiome and disease severity.Methods Stable bronchiectasis patients were enrolled in an international cohort study (n=269). IL-1β was measured in sputum supernatant. A validation cohort also had sputum rheology and hydration measured (n=53). For analysis, patients were stratified according to the median value of IL-1β in the population (high versus low) to compare disease severity, airway infection, microbiome (16S rRNA sequencing), inflammation and caspase-1 activity. Primary human nasal epithelial cells grown in air–liquid interface culture were used to study the effect of IL-1β on cilia function.Results Patients with high sputum IL-1β had more severe disease, increased caspase-1 activity and an increased T-helper type 1, T-helper type 2 and neutrophil inflammatory response compared with patients with low IL-1β. The active-dominant form of IL-1β was associated with increased disease severity. High IL-1β was related to higher relative abundance of Proteobacteria in the microbiome and increased mucus solid content and viscoelastic properties. Chronic IL-1β treatment reduced the functionality of cilia and tight junctions of epithelial cells in vitro.Conclusions A subset of stable bronchiectasis patients show increased airway IL-1β, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction.Airway IL-1β is a marker of severe disease, mucus hyperconcentration, Proteobacteria-dominant microbiome and Th1, Th2 and neutrophilic inflammation in bronchiectasis patients. In vitro, IL-1β directly impairs cilia function and epithelial integrity. https://bit.ly/4aeooF7