Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4delta2

J Allergy Clin Immunol. 1999 Nov;104(5):978-82. doi: 10.1016/s0091-6749(99)70078-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alternative Splicing*
  • Asthma / immunology*
  • Asthma / pathology
  • Biopsy
  • Bronchi / immunology
  • Bronchi / pathology
  • Cells, Cultured
  • Female
  • Humans
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics*
  • Leukocytes, Mononuclear / cytology
  • Male
  • Middle Aged
  • Nasal Polyps / immunology
  • Nasal Polyps / pathology
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sensitivity and Specificity


  • RNA, Messenger
  • Interleukin-4