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.