Mediators of neutrophil function in children with protracted bacterial bronchitis

• Published in: Chest Vol. 146; no. 4; p. 1013
• Main Authors: Baines, Katherine J, Upham, John W, Yerkovich, Stephanie T, Chang, Anne B, Marchant, Julie M, Carroll, Melanie, Simpson, Jodie L, Gibson, Peter G
• Format: Journal Article
• Language: English
• Published: United States 01.10.2014
• Subjects: alpha-Defensins - genetics; alpha-Defensins - metabolism; Bacterial Infections - genetics; Bacterial Infections - metabolism; Blotting, Western; Bronchitis - genetics; Bronchitis - metabolism; Bronchoalveolar Lavage Fluid - immunology; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin 1 Receptor Antagonist Protein - genetics; Interleukin 1 Receptor Antagonist Protein - metabolism; Interleukin-1 - genetics; Interleukin-1 - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Male; Neutrophils - physiology; Real-Time Polymerase Chain Reaction
• ISSN: 1931-3543
• DOI: 10.1378/chest.14-0131

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. 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. 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. 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.