Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats.
To examine whether fluticasone propionate (FP) dose-dependently inhibits inflammatory as well as structural changes, Brown Norway rats were sensitised to ovalbumin (OA) on day 0 and 7. From day 14-28, rats were exposed to aerosolised OA (1%) or phosphate buffered saline every 2 days. Thirty minutes before each allergen exposure, animals were pre-treated with aerosolised placebo or FP (0.1, 1 or 10 mg) or prednisolone 3 mg x kg(-1) i.p. At day 29, 0.1 mg FP had no measurable effect, either on inflammatory or structural changes, such as goblet cell hyperplasia and airway wall thickening. The allergen-induced increase in eosinophilic inflammation in bronchoalveolar lavage fluid and in the airway mucosa, as well as increased fibronectin deposition, were inhibited by treatment with FP from a dose of 1 mg onwards. Inhibition of goblet cell hyperplasia and thickening of the airway wall required 10 mg inhaled FP. At this dose, systemic effects were observed. However, for a comparable degree of systemic activity, prednisolone was far less effective at preventing airway changes. The dose of inhaled fluticasone propionate required to inhibit allergen-induced structural alterations was higher than to prevent eosinophil influx, and caused systemic side-effects. However, for a similar systemic activity, prednisolone was ineffective in preventing airway remodelling.
Vanacker
N J
NJ
Dept of Respiratory Diseases, Ghent University Hospital, Belgium. Nele.Vanacker@barclab.com
Palmans
E
E
Pauwels
R A
RA
Kips
J C
JC
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000068298:Fluticasone; D008297:Male; D010047:Ovalbumin; D011336:Probability; D051381:Rats; D011914:Rats, Inbred BN; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000730:Androstadienes; D010047:Ovalbumin; D000068298:Fluticasone