Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction.
Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kappaB and AP-1 in bronchial cells of RAO-affected horses. Seven horses with RAO were exposed to moldy hay until they developed airway obstruction on 3 separate occasions. In a crossover design, they were then treated with a placebo (injection on day 1), inhaled beclomethasone (500 microg q12h for 10 days), or dexamethasone (0.06 mg/kg, IM on day 1) and monitored for 10 days. Pulmonary function, bronchoalveolar lavage fluid cytology, and NF-kappaB and AP-1 activity in bronchial brushing cells were measured before (day 1) and after treatment (day 10). Treatment with beclomethasone resulted in significantly improved pulmonary function of RAO-affected horses compared with placebo and dexamethasone treatments. However, none of the treatments had an effect on bronchoalveolar lavage fluid cytology or NF-kappaB and AP-1 activity. These findings reveal that, in a model of severe RAO, the benefits of low-dose inhaled beclomethasone on pulmonary function are not accompanied by a decrease in airway inflammatory cells or a suppression of transcription factors NF-kappaB and AP-1 DNA-binding activity.
Couëtil
Laurent L
LL
Department of Physiology, Faculty of Veterinary Medicine, University of Liège, Belgium. couetill@purdue.edu
Art
Tatiana
T
de Moffarts
Brieuc
B
Becker
Martine
M
Mélotte
Dorothée
D
Jaspar
Fabrice
F
Bureau
Fabrice
F
Lekeux
Pierre
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001507:Beclomethasone / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D018592:Cross-Over Studies; D003908:Dexamethasone Isonicotinate / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D012138:Respiratory Therapy; D014157:Transcription Factors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D014157:Transcription Factors; D003908:Dexamethasone Isonicotinate; D001507:Beclomethasone