The effects of inhaled budesonide on circulating eosinophil progenitors and their expression of cytokines after allergen challenge in subjects with atopic asthma.
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.
Gauvreau
G M
GM
Asthma Research Group, St. Joseph's Hospital, Hamilton, Ontario, Canada.
Wood
L J
LJ
Sehmi
R
R
Watson
R M
RM
Dorman
S C
SC
Schleimer
R P
RP
Denburg
J A
JA
O'Byrne
P M
PM
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
D000485:Allergens; D001993:Bronchodilator Agents; D016207:Cytokines; D019819:Budesonide