The effects of intranasal budesonide on allergen-induced production of interleukin-5 and eotaxin, airways, blood, and bone marrow eosinophilia, and eosinophil progenitor expansion in sensitized mice.
We have previously demonstrated that allergen inhalation induces expansion of bone marrow eosinophil progenitors in sensitized mice and subjects with asthma and that the inhaled corticosteroid, budesonide, reduced baseline but not allergen-induced increase in bone marrow eosinophil/basophil progenitors (EoB-CFU) in subjects with asthma. Here, we evaluated the effects of intranasal budesonide on allergen-induced increases in interleukin (IL)-5 and eotaxin in the airway and peripheral blood, expansion of bone marrow Eo-CFU and eosinophilia in bone marrow, peripheral blood and airway, as well as airway hyperresponsiveness, in ovalbumin (OVA)-sensitized mice. Budesonide treatment attenuated allergen-induced eosinophilia in bone marrow, peripheral blood, and airways as well as allergen-induced increases in bone marrow eosinophil progenitors but not allergen-induced increases in IL-5 or eotaxin 12 h following the second of two daily exposures to allergen; at later time points treatment was associated with attenuation of IL-5, eosinophilia, Eo-CFU, and airway hyperresponsiveness. These results suggest that a component of the mechanism by which corticosteroid treatment attenuates allergen-induced airway inflammation is through suppression of bone marrow eosinophilopoiesis, and that this is likely not mediated simply through the blocking of IL-5 production at the airway.
Asthma Research Group, Department of Medicine, McMaster University and St. Joseph's Hospital, Hamilton, Ontario, Canada.
Huahao
H
Shen
Paul M
PM
O'Byrne
Russ
R
Ellis
Jennifer
J
Wattie
Chibing
C
Tang
Mark D
MD
Inman
D000281:Administration, Intranasal; D000403:Airway Resistance; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism*; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology*; D005260:Female; D005938:Glucocorticoids; D006412:Hematopoietic Stem Cells; D007114:Immunization; D015848:Interleukin-5 / Q000378:metabolism*; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D005938:Glucocorticoids; D015848:Interleukin-5; D019819:Budesonide; D010047:Ovalbumin