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  • Title: Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis.
    Author: Perea L, Bottier M, Cant E, Richardson H, Dicker AJ, Shuttleworth M, Giam YH, Abo-Leyah H, Finch S, Huang JT, Shteinberg M, Goeminne PC, Polverino E, Altenburg J, Blasi F, Welte T, Aliberti S, Sibila O, Chalmers JD, Shoemark A.
    Journal: Eur Respir J; 2024 Aug; 64(2):. PubMed ID: 38811046.
    Abstract:
    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.
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