Abstract
We have measured the expression of messenger ribonucleic acid (RNA) (mRNA) encoding interleukin-5 (IL-5), IL-4, IL-2 and interferon-gamma (IFN gamma) in peripheral blood mononuclear cells (PBMC) from 10 patients with acute exacerbations of asthma and nine non-asthmatic controls. Measurements were repeated in seven of the asthmatics following 7 days of oral glucocorticoid therapy. Total RNA was extracted from the PBMC, reverse transcribed using oligo-(dT) primers and aliquots of the resulting complementary DNA (cDNA) amplified using the polymerase chain reaction (PCR) in the presence of cytokine-specific primers under non-saturating conditions. PCR products were quantified on a relative basis after Southern blotting and probing with radiolabelled internal oligonucleotide probes by computer assisted densitometry of blot autoradiographs. The relative amounts of IL-5 mRNA in PBMC from the asthmatic patients prior to glucocorticoid therapy were greater (P < 0.01) than those in PBMC from non-asthmatic controls. In contrast, there were no differences in the relative amounts of IL-4, IL-2 and IFN gamma mRNA. In the asthmatics, the relative amounts of IL-5 mRNA correlated with the peripheral blood eosinophil counts (P = 0.02). After oral glucocorticoid therapy of the asthmatics, lung function improved and the relative amounts of PBMC IL-5 mRNA were reduced (P = 0.04) and no longer differed from those in PBMC from non-asthmatic controls. Glucocorticoid therapy was not associated with significant changes in the relative amounts of PBMC IL-4, IL-2 and IFN gamma mRNA. PBMC from atopic subjects contained significantly greater quantities of IL-4 mRNA (P = 0.04) but not IL-5, IL-2 and IFN gamma mRNA compared with non-atopic subjects regardless of their asthmatic status. We conclude that PBMC of patients with acute exacerbations of asthma demonstrate elevated expression of mRNA encoding IL-5, but not IL-2, IL-4 and IFN gamma and that the clinical improvement associated with glucocorticoid therapy is associated with a reduction of IL-5 mRNA expression. We further conclude that elevated expression in PBMC of mRNA encoding IL-4 is a feature of atopy but not of asthma. These observations suggest that IL-5 synthesis by activated T-lymphocytes may be relevant to the pathogenesis of asthma, and that inhibition of this release by glucocorticoids may at least partly explain their therapeutic effect in this disease.
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