Interleukin-5 in growth and differentiation of blood eosinophil progenitors in asthma: Effect of glucocorticoids

There are increased numbers of circulating CD34⁺ progenitor cells for eosinophils in patients with atopic asthma, with a further increase following allergen exposure or spontaneous worsening of asthma. We investigated the expression of IL-5 and IL-5Rα receptor in circulating CD34⁺ progenitor cells in allergic asthmatics and the effects of corticosteroids. Using double-staining techniques, up to 50% of CD34⁺ cells expressed intracellular IL-5, and by RT-PCR, there was significant expression of IL-5 mRNA. When cultured in a semi-liquid methylcellulose medium, there were more eosinophil colony-forming units grown from asthmatic non-adherent mononuclear cell depleted of T cells in the presence of the growth factors GM-CSF, SCF and IL-3, but not of IL-5. An anti-IL-5Rcα receptor antibody and an anti-sense IL-5 oligonucleotide reduced the number of eosinophil colony forming units. No IL-5 mRNA or protein expression on T cells was observed in asthmatics or normal subjects. In the presence of growth factors including IL-5, there were significantly greater colony numbers with eosinophilic lineage grown from either asthmatics or normal subjects. Dexamethasone (10^-6 M) suppressed IL-5 mRNA and protein expression in CD34⁺ cells, and reduced eosinophil colony-forming units in asthmatics, but not in normal subjects. Dexamethasone did not change the expression of IL-5Rα on CD34⁺ cells. We conclude that there is increased expression of IL-5 on blood CD34⁺ cells of patients with asthma and that this expression may auto-regulate eosinophilic colony formation from these progenitor cells. Corticosteroids inhibit the expression of IL-5 in circulating CD34⁺ progenitor cells.