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Am. J. Respir. Crit. Care Med., Volume 159, Number 5, May 1999, 1457-1463

An Inhaled Corticosteroid, Budesonide, Reduces Baseline but Not Allergen-induced Increases in Bone Marrow Inflammatory Cell Progenitors in Asthmatic Subjects

LORNA J. WOOD, ROMA SEHMI, GAIL M. GAUVREAU, RICHARD M. WATSON, RONAN FOLEY, JUDAH A. DENBURG, and PAUL M. O'BYRNE

Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

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 µg/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.




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