title: The effects of inhaled budesonide on circulating eosinophil progenitors and their expression of cytokines after allergen challenge in subjects with atopic asthma.
abstract: 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.
authors: Asthma Research Group, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors: G M
authors: GM
authors: Gauvreau
authors: L J
authors: LJ
authors: Wood
authors: R
authors: R
authors: Sehmi
authors: R M
authors: RM
authors: Watson
authors: S C
authors: SC
authors: Dorman
authors: R P
authors: RP
authors: Schleimer
authors: J A
authors: JA
authors: Denburg
authors: P M
authors: PM
authors: O'Byrne
mesh_terms: D000280:Administration, Inhalation; D000485:Allergens; D000704:Analysis of Variance; D001249:Asthma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests / Q000379:methods / Q000706:statistics & numerical data; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D003114:Colony-Forming Units Assay / Q000379:methods / Q000706:statistics & numerical data; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
chemical_list: D000485:Allergens; D001993:Bronchodilator Agents; D016207:Cytokines; D019819:Budesonide