Interleukin-4 and its alternatively spliced variant (IL-4δ2) in patients with atopic asthma

The interleukin-4 (IL-4) splice variant (IL-4 delta2) 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-4 delta2. This is the first study to examine patients with chronic asthma and atopy for IL-4 delta2 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-4 delta2 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-4 delta2 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-4 delta2 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.