title: Increased expression of interleukin-16 in bronchial mucosa of subjects with atopic asthma.
abstract: Asthma is characterized by the presence of activated CD4+ cells in the airways. We hypothesized that the newly characterized cytokine interleukin (IL)-16 is involved in the pathogenesis of asthma through its ability to selectively induce CD4+ cell recruitment within the inflamed bronchial wall. We investigated the expression of IL-16 in bronchial biopsies obtained from subjects with mild asthma (n = 10), atopic nonasthmatic individuals (n = 6), and normal control subjects (n = 10). Cryostat sections from 4% paraformaldehyde-fixed fiberoptic bronchial biopsies were immunostained using a specific antibody that recognizes human IL-16. IL-16 mRNA expression was determined by in situ hybridization. IL-16 immunoreactivity and mRNA were demonstrated mainly in bronchial epithelial cells in all subjects. IL-16 immunoreactivity and IL-16 mRNA expression within the epithelium were significantly higher in bronchial biopsies obtained from asthmatic subjects as compared to both atopic nonasthmatic and normal controls (P < 0.001). The numbers of subepithelial IL-16 immunoreactive cells and IL-16 mRNA-positive cells were also greater in the bronchial biopsies obtained from asthmatic subjects as compared to both atopic nonasthmatic and normal controls (P < 0.001). Epithelial expression of IL-16 immunoreactivity and mRNA correlated with the CD4+ cell infiltration (r2 = 0.70, P < 0.001). There were significant associations between epithelial and subepithelial IL-16 immunoreactivity and airway responsiveness to methacholine. This study demonstates that IL-16 is expressed in airway tissues, particularly in the epithelial cells, and that up-regulation of its expression is a feature of allergic asthma. These results suggest an in vivo role for IL-16 in the pathogenesis of asthma, possibly through the recruitment of CD4+ cells, and support the increasing evidence for the participation of epithelial cells in regulating inflammatory responses.
authors.affiliation: Meakins-Christie Laboratories and Montreal General Hospital, McGill University, Canada. labergso@magellan.umontreal.ca
authors.forename: S
authors.initials: S
authors.lastname: Laberge
authors.forename: P
authors.initials: P
authors.lastname: Ernst
authors.forename: O
authors.initials: O
authors.lastname: Ghaffar
authors.forename: W W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: H
authors.initials: H
authors.lastname: Kornfeld
authors.forename: D M
authors.initials: DM
authors.lastname: Center
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D006801:Humans; D019410:Interleukin-16 / Q000235:genetics*; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D019410:Interleukin-16; D012333:RNA, Messenger