The Effects of Inhaled Budesonide on Circulating Eosinophil Progenitors and Their Expression of Cytokines after Allergen Challenge in Subjects with Atopic Asthma
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Allergen inhalation by dual responder subjects with atopic asthma is associated with an increase in circulating eosinophil/basophil colony-forming units (Eo/B CFU) and granulocyte-macrophage colony- stimulating factor (GM-CSF) immunolocalization in Eo/B colony cells grown in vitro. The current study examined the effect of the inhaled corticosteroid, budesonide, on the number of allergen- induced circulating eosinophils and Eo/B CFU, and immunolocalization of GM-CSF and interleukin-5 (IL-5) in Eo/B colony cells grown in vitro. Sixteen subjects with mild atopic asthma were treated for either 7 or 8 d with 200 microg inhaled budesonide or placebo twice a day. Peripheral blood was collected before and 24 h after allergen inhalation challenge and nonadherent mononuclear cells (NAMC) were grown in methylcellulose culture. Eo/B CFU were enumerated after 14 d in culture, and prepared on slides for immunocytochemistry. Budesonide attenuated the allergen-induced increase in circulating eosinophils (4.0 +/- 0.4 x 10(5)/ml versus 6.5 +/- 0.7 x 10(5)/ml, p = 0.0001), circulating Eo/B CFU (12.4 +/- 2.3/10(6) NAMC versus 18.8 +/- 4.6/10(6) NAMC, p = 0.05), and immunolocalization of GM-CSF in Eo/B colony cells (11.8 +/- 1.9% positive versus 18.0 +/- 2.2%, p = 0.01) but not immunolocalization of IL-5 (7.9 +/- 1.4% versus 4.5 +/- 0.6%, p > 0.05). Inhaled budesonide attenuated the number of allergen-induced circulating eosinophils and their progenitors grown in the presence of GM-CSF, which may partially be a result of regulating eosinophil progenitor expression of the autocrine growth factor GM-CSF.
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