Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis.

Abstract

The inflammasome is a key regulatory complex of the inflammatory response leading to 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. To characterize the role of airway IL-1β in bronchiectasis including the association with mucus properties, ciliary function, airway inflammation, microbiome and disease severity. 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 IL-1β effect on cilia function. Patients with high sputum IL-1β had more severe disease, increased caspase-1 activity and increased Th1, Th2 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. 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.