Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4delta2.
BACKGROUND
The human IL4 gene, has been shown to express the alternatively spliced messenger (m)RNA IL-4delta2. IL-4delta2 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-4delta2 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-4delta2 mRNA from one reaction.


RESULTS
IL-4 and IL-4delta2 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/microg RNA; range, 0-3.7 x 10(3) copies/microg RNA) and asthmatic subjects (median, 1.4 x 10(2) copies/microg RNA; range, 0-4.7 x 10(2) copies/microg RNA). However, significantly more asthmatic subjects (6 of 9) than control subjects (1 of 7) expressed IL-4delta2 (P =. 036). Expression of IL-4 variants was unaffected by atopic status.


CONCLUSIONS
Given that IL-4delta2 is an IL-4 receptor antagonist, these results indicate that it is crucial to be able to distinguish IL-4delta2 from IL-4 when assessing IL4 gene expression. Increased expression of IL-4delta2 in stable asthmatic subjects suggests that the balance of IL-4 and IL-4delta2 may modulate asthmatic inflammation.
Glare
E M
EM
Department of Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia.
Divjak
M
M
Rolland
J M
JM
Walters
E H
EH
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
D012333:RNA, Messenger; D015847:Interleukin-4