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Mediators of neutrophil function in children with protracted bacterial bronchitis.
- Source :
-
Chest [Chest] 2014 Oct; Vol. 146 (4), pp. 1013-1020. - Publication Year :
- 2014
-
Abstract
- Background: Protracted bacterial bronchitis (PBB) is a common and treatable cause of chronic wet cough in children in which the mechanisms are not understood. This study investigates the IL-1 pathway and a neutrophil gene expression signature in PBB.<br />Methods: BAL was collected from children in an experimental cohort (n = 21, PBB; n = 33, control subjects), and a second validation cohort (n = 36, PBB; n = 11, control subjects). IL-1β, IL-1 receptor antagonist (IL-1RA), and α-defensins 1-3 were assayed by enzyme-linked immunosorbent assay, western blot, and quantitative real-time polymerase chain reaction, together with selected IL-1 pathway members and neutrophil-related molecules.<br />Results: In the experimental cohort, children with symptomatic PBB had significantly higher levels of IL-1β and α-defensin gene and protein expression. Expression of the neutrophil chemokine receptor C-X-C motif receptor 2 was also higher in PBB. IL-1RA protein was higher, however, the IL-1RA:IL-1β ratio was lower in children with PBB than control subjects. In the validation cohort, protein and gene expression of IL-1β and α-defensins 1-3 were confirmed higher, as was gene expression of IL-1 pathway members and C-X-C motif receptor 2. IL-1β and α-defensin 1-3 levels lowered when PBB was treated and resolved. In children with recurrent PBB, gene expression of the IL-1β signaling molecules pellino-1 and IL-1 receptor-associated kinase 2 was significantly higher. IL-1β protein levels correlated with BAL neutrophilia and the duration and severity of cough symptoms. IL-1β and α-defensin 1-3 levels were highly correlated.<br />Conclusions: PBB is characterized by increased IL-1β pathway activation. IL-1β and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.
- Subjects :
- Bacterial Infections genetics
Blotting, Western
Bronchitis genetics
Child
Child, Preschool
Enzyme-Linked Immunosorbent Assay
Female
Humans
Infant
Interleukin 1 Receptor Antagonist Protein genetics
Interleukin-1 genetics
Interleukin-1beta genetics
Male
Real-Time Polymerase Chain Reaction
alpha-Defensins genetics
Bacterial Infections metabolism
Bronchitis metabolism
Bronchoalveolar Lavage Fluid immunology
Interleukin 1 Receptor Antagonist Protein metabolism
Interleukin-1 metabolism
Interleukin-1beta metabolism
Neutrophils physiology
alpha-Defensins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1931-3543
- Volume :
- 146
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Chest
- Publication Type :
- Academic Journal
- Accession number :
- 24874501
- Full Text :
- https://doi.org/10.1378/chest.14-0131