Airway IL-1ß is related to disease severity and mucociliary function in bronchiectasis.
Eur Respir J
; 64(2)2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38811046
ABSTRACT
RATIONALE The inflammasome is a key regulatory complex of the inflammatory response leading to interleukin-1ß (IL-1ß) release and activation. IL-1ß amplifies inflammatory responses and induces mucus secretion and hyperconcentration in other diseases. The role of IL-1ß in bronchiectasis has not been investigated. OBJECTIVES:
To characterise the role of airway IL-1ß 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-1ß 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-1ß 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-1ß on cilia function.RESULTS:
Patients with high sputum IL-1ß 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-1ß. The active-dominant form of IL-1ß was associated with increased disease severity. High IL-1ß was related to higher relative abundance of Proteobacteria in the microbiome and increased mucus solid content and viscoelastic properties. Chronic IL-1ß 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-1ß, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Esputo
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Índice de Severidad de la Enfermedad
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Bronquiectasia
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Depuración Mucociliar
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Interleucina-1beta
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2024
Tipo del documento:
Article