High concentrations of middle ear antimicrobial peptides and proteins and proinflammatory cytokines are associated with detection of middle ear pathogens in children with recurrent acute otitis media

Autoři: Elke J. Seppanen aff001;  Ruth B. Thornton aff001;  Karli J. Corscadden aff001;  Caitlyn M. Granland aff001;  Julie Hibbert aff003;  Angela Fuery aff004;  Selma P. Wiertsema aff004;  Shyan Vijayasekaran aff005;  Harvey L. Coates aff006;  Peter Jacoby aff001;  Andrew Currie aff003;  Peter C. Richmond aff001;  Lea-Ann S. Kirkham aff001
Působiště autorů: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia aff001;  School of Biomedical Sciences, Faculty Health and Medical Science, University of Western Australia, Perth, Western Australia, Australia aff002;  Centre for Neonatal Research and Education, Faculty Health and Medical Science, University of Western Australia, Perth, Western Australia, Australia aff003;  School of Medicine, Division of Paediatrics, Faculty Health and Medical Science, University of Western Australia, Perth, Western Australia, Australia aff004;  Perth Children’s Hospital, Perth, Western Australia, Australia aff005;  School of Medicine, Otolaryngology Unit, Faculty Health and Medical Science, University of Western Australia, Perth, Western Australia, Australia aff006;  Medical, Molecular & Forensic Sciences, Murdoch University, Perth, Western Australia, Australia aff007;  Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia aff008
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227080


Recurrent and chronic otitis media (OM) are often refractory to antibiotics due to bacterial persistence in biofilm within the middle ear. In vitro and in vivo studies have demonstrated that antimicrobial proteins and peptides (AMPs) are bactericidal against otopathogens, indicating potential therapeutic value for recalcitrant OM. We measured concentrations of 6 AMPs and 14 cytokines in middle ear effusion (MEE) from 67 children undergoing ventilation tube insertion for recurrent acute OM. Sixty one percent of children had bacterial otopathogens detected in their MEE, 39% by PCR and 22% by PCR and culture. Groups were defined as: PCR-negative/culture-negative (absence of bacterial otopathogen), n = 26; PCR-positive/culture-negative (presence of nonculturable bacterial otopathogen), n = 26; PCR-positive/culture-positive (presence of culturable bacterial otopathogen), n = 15. Age, antibiotic usage, day-care attendance, presence of respiratory viruses in MEE and number of AOM episodes were similar between groups. AMP and cytokine concentrations were higher in children with bacterial otopathogens in their MEE compared to those with no bacterial otopathogens. Median concentrations of AMPs (except HBD2) were 3 to 56-fold higher in MEE from children with bacterial otopathogens detected in their MEE (P ≤ 0.01). Similarly, median cytokine concentrations (except TGFβ) were >16-fold higher in MEE with bacterial otopathogens detected (P ≤ 0.001). This is the first study to measure AMPs in MEE and together with the cytokine data, results suggest that elevated AMPs and cytokines in MEE are a marker of inflammation and bacterial persistence. AMPs may play an important role in OM pathogenesis.

Klíčová slova:

Antibiotics – Bacterial biofilms – Bacterial pathogens – Cytokines – Children – Inflammatory diseases – Middle ear – Pathogenesis


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