Expression of the IL-4 Receptor Alpha-subunit is Increased in Bronchial Biopsy Specimens from Atopic and Nonatopic Asthmatic Subjects

Background: Recent studies have provided evidence for increased IL-4 expression in the airways of atopic and nonatopic asthmatic subjects. IL-4 is believed to perform important regulatory roles in asthma; however, the expression of the IL-4 receptor has not been investigated. In this study we examined the mRNA and protein expression of the specific alpha-subunit of the IL-4 receptor (alphaIL-4R) in bronchial biopsy specimens obtained from atopic and nonatopic asthmatic subjects.

Methods: Asthmatic subjects and nonasthmatic control subjects were recruited, and lung function measurements were performed before bronchoscopy. Endobronchial biopsy specimens were examined for the presence of alphaIL-4R mRNA and immunoreactivity by using in situ hybridization and immunocytochemistry, respectively.

Results: alphaIL-4R mRNA-positive and immunoreactive cells were detected in the epithelium and subepithelium in biopsy specimens from all subjects. Expression of alphaIL-4R mRNA and protein was significantly increased in the epithelium and subepithelium of biopsy specimens from atopic asthmatic subjects compared with atopic control subjects (P <.05 and P <.001, respectively). Epithelial alphaIL-4R mRNA expression and immunoreactivity did not differ significantly between nonatopic asthmatic subjects and nonatopic control subjects. Although the numbers of alphaIL-4R mRNA-positive cells were augmented in the submucosa of intrinsic asthmatic subjects compared with nonatopic control subjects (P <.05), alphaIL-4R immunoreactivity did not differ significantly between these groups. Increased alphaIL-4R immunoreactive signals were also detected in the endothelial cell layer in both atopic and intrinsic asthmatic subjects compared with atopic and nonatopic control subjects, respectively (P <.05). Combined in situ hybridization immunocytochemistry performed on biopsy sections from asthmatic and control subjects demonstrated alphaIL-4R mRNA expression in CD3-positive T cells and tryptasepositive mast cells, with T cells comprising the larger proportion of alphaIL-4R mRNA-positive cells. Numbers of alphaIL-4R mRNA-positive or immunoreactive cells did not correlate with CD3-positive cell numbers, numbers of IL-4 mRNA-positive cells, or indices of pulmonary function.

Conclusion: These results demonstrate constitutive alphaIL-4R expression in normal airways and enhanced expression in airway tissue from asthmatic individuals.