Allergen-induced changes in bone marrow progenitors and airway responsiveness in dogs.
An increased production of inflammatory cell progenitors (colony-forming cells, CFUs) may contribute to airway inflammation, since CFUs increase after allergen inhalation in asthmatics. We examined the effect of allergen inhalation, with or without budesonide pretreatment, on bone marrow CFU production in dogs with allergen-induced airway hyperresponsiveness. Allergen inhalation increased airway responsiveness (p < 0.001) as well as the number of CFUs induced in vitro by recombinant canine stem cell factor (p < 0.001) and granulocyte-colony-stimulating factor (p = 0.035). Budesonide reduced the allergen-induced increases in airway responsiveness (p = 0.005) and abolished the allergen-induced increases in the numbers of CFUs (p < 0.005). These findings provide the first direct evidence that allergen inhalation increases bone marrow granulocyte progenitor production and suggest that such increases may contribute to the development of airway hyperresponsiveness in asthma. The effectiveness of inhaled corticosteroids in asthma may result, in part, from effect on bone marrow production of inflammatory cells.
Denburg
J A
JA
Department of Medicine, McMaster University, Hamilton, Ont., Canada.
Woolley
M J
MJ
Ellis
R
R
Dahlback
M
M
O'Byrne
P M
PM
D000280:Administration, Inhalation; D000402:Airway Obstruction / Q000139:chemically induced* / Q000188:drug therapy; D000485:Allergens / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D019819:Budesonide; D003114:Colony-Forming Units Assay; D004285:Dogs; D006098:Granulocytes / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D011282:Pregnenediones / Q000494:pharmacology / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*
D000485:Allergens; D011282:Pregnenediones; D019819:Budesonide