Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice.
Despite the effectiveness of corticosteroids at resolving airway inflammation, they are only moderately effective at attenuating airway hyperresponsiveness (AHR). The extent to which corticosteroids are able to reverse or inhibit the development of sustained AHR is not known. The present study aimed to determine whether budesonide can resolve and or prevent the development of sustained AHR in mice. Mice were chronically exposed to allergen and treated with budesonide either: 1) briefly during the final weeks of exposure to allergen; 2) prolonged concurrently throughout exposure to allergen; or 3) delayed following final exposure to allergen. AHR was assessed 24 h (brief treatment) or 4 weeks (prolonged concurrent and delayed treatments) following final exposure to allergen. Brief budesonide intervention significantly attenuated the inflammation-associated AHR assessed immediately following final exposure to allergen. Similarly, prolonged concurrent budesonide treatment prevented the development of sustained AHR. Delayed budesonide intervention, however, did not resolve sustained AHR. In conclusion, the early introduction and, importantly, the persistence of corticosteroid treatment prevented the development of sustained airway hyperresponsiveness; however, the inability of corticosteroids to reverse established airway dysfunction indicates a limitation in their use for the complete, long-term management of airway hyperresponsiveness.
Southam
D S
DS
Firestone Institute for Respiratory Health, Dept of Medicine, McMaster University, Hamilton, ON, Canada.
Ellis
R
R
Wattie
J
J
Young
S
S
Inman
M D
MD
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000485:Allergens / Q000737:chemistry; D000818:Animals; D001993:Bronchodilator Agents / Q000627:therapeutic use; D019819:Budesonide / Q000627:therapeutic use*; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000485:Allergens; D001993:Bronchodilator Agents; D019819:Budesonide; D003094:Collagen