Expression of wildtype and alternatively spliced interleukin-4 (IL-4) mRNA in bronchoalveolar lavage (BAL) cells from humans with allergic asthma

We previously identified a naturally occurring variant of human IL-4 mRNA in which the second exon is omitted by alternative splicing. This variant, IL-4δ2, inhibits IL-4-stimulated T cell proliferation, apparently through competitive binding to IL-4 receptors. We hypothesize that underproduction of IL-4δ2, relative to IL-4, contributes to the development of allergic asthma. To begin to test this hypothesis, RT-PCR was used to measure levels of IL-4 and IL-4δ2 mRNA in BAL cells from 4 ragweedsensitive asthmatics before and after installation of ragweed into their lungs. IL-4 and IL-4δ2 cDNAs were PCR amplified in the same tubes. Data are given as arbritrary Phosphorlmager units. IL-4δ2 mRNA was the predominant form of mRNA seen in baseline BAL cells, before ragweed. Similar results were also seen in BAL cells from 8 normal donors (data not shown). After ragweed challenge, IL-4 mRNA increased disproportionately more, increasing the ratio of IL-4:IL-4δ2 mRNA. More patients are currently being tested to extend these results. These data support the hypothesis that the allergic phenotype may include the relative underproduction of IL-4δ2 after allergen exposure. IL-4 and IL-4δ2 RNA in BAL Cells Before Ragweed After Ragweed IL-4 δ2 IL-4 δ2 Pt1-BAL 77 210 399 284 Pt2-BAL 149 407 209 426 Pt 3-BAL 0 40 84 180 Pt 4-BAL 0 16 539 115 Pt 1 - Blood 674 176 805 200 Pt 2-Blood 845 438 810 524.