Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4δ2

Background: The human IL4 gene, has been shown to express the alternatively spliced messenger (m)RNA IL-4 delta 2. IL-4 delta 2 is missing the entire sequence from exon 2 and has been identified as an IL-4 receptor antagonist. Objective: We sought to distinguish IL-4 and IL-4 delta 2 mRNA in respiratory tract tissue for the first time. Methods: A novel competitive PCR assay was established with primers designed on either side of the alternative splice junction of the IL4 gene, allowing the simultaneous quantitation of both IL-4 and IL-4 delta 2 mRNA from one reaction. Results: IL-4 and IL-4 delta 2 were differentially expressed in 4 nasal polyps. No difference was seen in endobronchial biopsy specimens for IL-4 mRNA expression between control subjects (median, 2.8 x 10(2) copies/mu g RNA; range, 0-3.7 x 10(3) copies/mu g RNA) and asthmatic subjects (median, 1.4 x 10(2) copies/mu g RNA; range, 0-4.7 x 10(2) copies/mu g RNA), However, significantly more asthmatic subjects (6 of 9) than control subjects (1 of 7) expressed IL-4 delta 2 (P = .036), Expression of IL-4 variants was unaffected by atopic status. Conclusions: Given that IL-4 delta 2 is an IL-4 receptor antagonist, these results indicate that it is crucial to be able to distinguish IL-4 delta 2 from IL-4 when assessing IL4 gene expression. Increased expression of IL-4 delta 2 in stable asthmatic subjects suggests that the balance of IL-4 and IL-4 delta 2 may modulate asthmatic inflammation.