Interleukin‐5 in growth and differentiation of blood eosinophil progenitors in asthma: effect of glucocorticoids

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Abstract
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‐5Rα 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. British Journal of Pharmacology (2001) 134, 1539–1547; doi:10.1038/sj.bjp.0704389

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