An inhaled corticosteroid, budesonide, reduces baseline but not allergen-induced increases in bone marrow inflammatory cell progenitors in asthmatic subjects.
We have previously shown that allergen inhalation by asthmatics is associated with increases in bone marrow eosinophil/basophil colony-forming cells (Eo/B-CFU), and increases in CD34(+) hemopoietic progenitors expressing the alpha-subunit of the IL-5 receptor (IL-5Ralpha). This study investigated the effect of inhaled corticosteroid on baseline numbers and allergen-induced increases in these parameters. Nine subjects with mild, stable asthma inhaled budesonide (400 microgram/d) for 8 d in a placebo-controlled, double-blind, randomized crossover study. On Day 7, subjects inhaled allergen, with bone marrow sampling before and 24 h after challenge. Budesonide inhalation significantly attenuated the allergen-induced early and late asthmatic responses, degree of increase in sputum and blood eosinophils, as well as the baseline numbers of total bone marrow CD34(+) cells (p < 0.05), CD34(+)IL-3Ralpha+ cells (p < 0.01) and IL-5-responsive Eo/B-CFU (p < 0.05). Allergen inhalation significantly increased Eo/B-CFU grown in the presence of IL-3, GM-CSF, or IL-5 alone (p < 0.05) and in combination (p < 0.01), as well as the number of CD34(+)IL-5Ralpha+ cells (p < 0.01). However, these increases in Eo/B-CFU and CD34(+)IL-5Ralpha+ cells were not affected by budesonide treatment. These data demonstrate that short-term inhaled budesonide treatment has a systemic effect in inhibiting the turnover of a subpopulation of bone-marrow-derived progenitors, but that inhalation of allergen overcomes this inhibitory effect.
Wood
L J
LJ
Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Sehmi
R
R
Gauvreau
G M
GM
Watson
R M
RM
Foley
R
R
Denburg
J A
JA
O'byrne
P M
PM
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000473:pathology*; D001491:Basophils / Q000473:pathology; D001773:Blood Cells / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology*; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology; D013183:Sputum / Q000166:cytology; D013234:Stem Cells / Q000473:pathology*
D000485:Allergens; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D019819:Budesonide