INCREASED EXPRESSION OF INTERLEUKIN-16 IN BRONCHIAL-MUCOSA OF SUBJECTS WITH ATOPIC ASTHMA

Asthma is characterized by the presence of activated CD4(+) cells in t he airways. We hypothesized that the newly characterized cytokine inte rleukin (IL)-16 is involved in the pathogenesis of asthma through its ability to selectively induce CD4(+) cell recruitment within the infla med bronchial wall. We investigated the expression of IL-16 in bronchi al biopsies obtained from subjects with mild asthma (n = 10), atopic n onasthmatic 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 hybridiz ation. IL-16 immunoreactivity and mRNA were demonstrated mainly in bro nchial 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 bo th atopic nonasthmatic and normal controls (P < 0.001). The numbers of subepithelial IL-16 immunoreactive cells and lL-16 mRNA-positive cell s were also ter in the bronchial biopsies obtained from asthmatic subj ects as compared to both atopic nonasthmatic and normal controls (P < 0.001). Epithelial expression of IL-16 immunoreactivity and mRNA corre lated with the CD4(+) cell infiltration (r(2) = 0.70, P < 0.001). Ther e were significant associations between epithelial and subepithelial I L-16 immunoreactivity and airway responsiveness to methacholine. This study demonstates that IL-16 is expressed in airway tissues, particula rly in the epithelial cells: and that upregulation of its expression i s a feature of allergic asthma. These results suggest an in vivo role for IL-16 in the pathogenesis of asthma, possibly through the recruitm ent of CD4(+) cells, and support the increasing evidence for the parti cipation of epithelial cells in regulating inflammatory responses.