Am. J. Respir. Crit. Care Med., Volume 164, Number 6, September 2001, 1016-1018

Interleukin-4 and Its Alternatively Spliced Variant (IL-42) in Patients with Atopic Asthma

GEOK TENG SEAH, PEI SONG GAO, JULIAN M. HOPKIN, and GRAHAM A. W. ROOK

Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, London, United Kingdom; Department of Microbiology, National University of Singapore, Singapore; and Experimental Medicine Unit, University of Wales, Swansea, United Kingdom

The interleukin-4 (IL-4) splice variant (IL-42) is known to antagonize many biological activities of IL-4, and this challenges our understanding of the role of IL-4 in asthma. Studies that have used nonspecific antibodies, probes, and/or primers to quantify IL-4 in clinical samples would not have distinguished the expression of IL-4 from IL-42. This is the first study to examine patients with chronic asthma and atopy for IL-42 mRNA in their peripheral blood mononuclear cells without antigen stimulation, using a quantitative nested reverse-transcription polymerase chain reaction (RT-PCR) protocol. The median IL-4 mRNA copy number in cells from the patients with asthma was 2.8 logs higher than in a comparator group of patients with tuberculosis (p = 0.0005) and 4.5 logs higher (p = 0.0004) than in healthy control subjects. In contrast, IL-42 expression in cells from patients with asthma was similar to that seen in cells from patients with tuberculosis. Hence, the median ratio of IL-4 to IL-42 was 500-fold higher in the patients with asthma when compared with either patients with tuberculosis or healthy control subjects. The relative expression of IL-4 and IL-42 may be a reason for the functional diversity of Th2 cells in different clinical conditions, and a hitherto unexplored mechanism for the pulmonary pathology in patients with atopic asthma.

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