4.4 Article

Pseudomonas aeruginosa colonization in cystic fibrosis: Impact on neutrophil functions and cytokine secretion capacity

Journal

PEDIATRIC PULMONOLOGY
Volume 56, Issue 6, Pages 1504-1513

Publisher

WILEY
DOI: 10.1002/ppul.25294

Keywords

CAP‐ 18; cystic fibrosis; cytokines; neutrophils

Funding

  1. Istanbul University [49604]

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The functional properties of neutrophils in CF patients with P. aeruginosa colonization were analyzed in this study. Differences in migration, phagocytosis, oxidative burst, IL-8 production, and inflammatory cytokine secretion were noted among CF patients based on their colonization status, potentially leading to further airway damage and unfavorable prognosis in children with CF and colonization.
Background Chronic colonization with Pseudomonas (P.) aeruginosa worsens the prognosis of cystic fibrosis (CF) patients. This study aims to analyze the functional properties of neutrophils in CF patients with P. aeruginosa colonization. Methods Patients with CF (n = 16) were grouped by positivity of P. aeruginosa in sputum culture, as positive (P.+) or negative (P.-), then compared with age and sex matched healthy controls (n = 8). Adhesion molecules, apoptotic index, intracellular CAP-18, interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) levels of neutrophils, following P. aeruginosa and lipopolysaccharides (LPS) stimulation, were analyzed by flow cytometry. IL-1 beta, IL-6, TNF-alpha, and IL-17 plasma levels were determined by Luminex. Results Patients with CF had increased phagocytosis of Escherichia coli and P. aeruginosa, upregulated oxidative burst and chemotaxis. Increased neutrophil apoptosis was noted in CF patients. In unstimulated conditions, higher levels of CD16(+)TNF-alpha(+) and CD16(+)IL-8(+) neutrophils were determined, whereas bacteria and LPS stimulation significantly decreased secretion of CAP-18 from CD16(+) neutrophils of CF patients. Plasma levels of IL-1 beta, TNF-alpha and IL-17 in P.+ patients were higher than in P.- group. Conclusion Our findings confirm inadequate neutrophil defense towards pathogens in CF. A significant difference in migration, phagocytosis, oxidative burst, percentage of IL-8 producing neutrophils, IL-1 beta, TNF-alpha, and IL-17 secretions were noted among CF patients according to their colonization status, which might induce a further destructive effect on airways, resulting in an unfavorable prognosis for children with CF who also have colonization.

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