title: The role of IL-15 deficiency in the pathogenesis of virus-induced asthma exacerbations.
abstract: Rhinovirus infections are the major cause of asthma exacerbations. We hypothesised that IL-15, a cytokine implicated in innate and acquired antiviral immunity, may be deficient in asthma and important in the pathogenesis of asthma exacerbations. We investigated regulation of IL-15 induction by rhinovirus in human macrophages in vitro, IL-15 levels in bronchoalveolar lavage (BAL) fluid and IL-15 induction by rhinovirus in BAL macrophages from asthmatic and control subjects, and related these to outcomes of infection in vivo. Rhinovirus induced IL-15 in macrophages was replication-, NF-κB- and α/β interferon-dependent. BAL macrophage IL-15 induction by rhinovirus was impaired in asthmatics and inversely related to lower respiratory symptom severity during experimental rhinovirus infection. IL-15 levels in BAL fluid were also decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection. Deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations.
authors.affiliation: Department of Respiratory Medicine, National Heart and Lung Institute, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infection, Imperial College London, London, United Kingdom.
authors.forename: Vasile
authors.initials: V
authors.lastname: Laza-Stanca
authors.forename: Simon D
authors.initials: SD
authors.lastname: Message
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.forename: Hayley L
authors.initials: HL
authors.lastname: Parker
authors.forename: Mihnea T
authors.initials: MT
authors.lastname: Zdrenghea
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kebadze
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.forename: Luminita A
authors.initials: LA
authors.lastname: Stanciu
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology; D019409:Interleukin-15; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D016328:NF-kappa B / Q000276:immunology; D010850:Picornaviridae Infections / Q000276:immunology* / Q000473:pathology; D012229:Rhinovirus / Q000276:immunology*; D019562:Viral Load / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D019409:Interleukin-15; D016328:NF-kappa B; D016899:Interferon-beta