title: Interleukin-15 is associated with disease severity in viral bronchiolitis.
abstract: Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity.A prospective single-centre observational study was conducted in a university-affiliated paediatric teaching hospital, comparing children (0-18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants.Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de-regulated miRNA were differentially expressed in bronchiolitis, including JAK3, STAT5A and NFKB1 on the IL-15 signalling pathway.IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis.
authors.affiliation: Dept of Paediatrics, Children's University Hospital, Dublin, Ireland Dept of Clinical Medicine, Trinity College, Dublin, Ireland ronan.leahy@olchc.ie.
authors.forename: T Ronan
authors.initials: TR
authors.lastname: Leahy
authors.affiliation: Dept of Clinical Medicine, Trinity College, Dublin, Ireland.
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
authors.affiliation: Dept of Immunology, Trinity College, Dublin, Ireland.
authors.forename: Derek G
authors.initials: DG
authors.lastname: Doherty
authors.affiliation: Dept of Clinical Medicine, Trinity College, Dublin, Ireland Dept of Critical Care Medicine, St James' Hospital, Dublin, Ireland.
authors.forename: Robert
authors.initials: R
authors.lastname: Grealy
authors.affiliation: Dept of Immunology, Trinity College, Dublin, Ireland.
authors.forename: Tanya
authors.initials: T
authors.lastname: Coulter
authors.affiliation: Dept of Histopathology, Sir Patrick Dun Research Laboratory, Trinity College, Dublin, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Smyth
authors.affiliation: Dept of Histopathology, Sir Patrick Dun Research Laboratory, Trinity College, Dublin, Ireland.
authors.forename: Gordon
authors.initials: G
authors.lastname: Blackshields
authors.affiliation: Dept of Histopathology, Sir Patrick Dun Research Laboratory, Trinity College, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Sheils
authors.affiliation: National Virus Reference Laboratory, University College Dublin, Dublin, Ireland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Carr
authors.affiliation: Dept of Obstetrics and Gynaecology, Rotunda Hospital, Dublin, Ireland.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Purandare
authors.affiliation: Dept of Obstetrics and Gynaecology, Rotunda Hospital, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Geary
authors.affiliation: University Medical Center, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Hennie M
authors.initials: HM
authors.lastname: Hodemaekers
authors.affiliation: University Medical Center, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Riny
authors.initials: R
authors.lastname: Janssen
authors.affiliation: University Medical Center, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
authors.affiliation: Dept of Paediatrics, Children's University Hospital, Dublin, Ireland.
authors.forename: Dubhfeasa
authors.initials: D
authors.lastname: Slattery
authors.affiliation: Dept of Critical Care Medicine, St James' Hospital, Dublin, Ireland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ryan
mesh_terms: D001990:Bronchiolitis, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D053616:Janus Kinase 3 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; C569274:IL15 protein, human; D019409:Interleukin-15; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D012333:RNA, Messenger; D020537:RNA, Small Nucleolar; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; C507933:JAK3 protein, human; D053616:Janus Kinase 3