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 associat ed 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-5R alpha). This study investigated t he effect of inhaled corticosteroid on baseline numbers and allergen-induce d increases in these parameters. Nine subjects with mild, stable asthma inh aled budesonide (400 mu g/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 sig nificantly attenuated the allergen-induced early and late asthmatic respons es, degree of increase in sputum and blood eosinophils, as well as the base line numbers of total bone marrow CD34(+) cells (p < 0.05), CD34(+)IL-3R al pha(+) cells (p < 0.01) and IL-5-responsive Eo/B-CFU (p < 0.05). Allergen i nhalation significantly increased Eo/B-CFU grown in the presence of IL-3, G M-CSF, or IL-5 alone (p < 0.05) and in combination (p < 0.01), as well as t he number of CD34(+)IL-5R alpha cells (p < 0.01). However, these increases in Eo/B-CFU and CD34(+)IL-5R alpha(+) cells were not affected by budesonide treatment. These data demonstrate that short-term inhaled budesonide treat ment 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.