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Copyright ©ERS Journals Ltd 2002
Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats
Dept of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium
CORRESPONDENCE: N.J. Vanacker, Dept of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, B-9000, Ghent, Belgium. Fax: 32 92402341. E-mail: Nele.Vanacker@barclab.com
Keywords: asthma, corticosteroids, dose-response, fluticasone, rats, remodelling
Received: December 12, 2001
Accepted May 28, 2002
N.J. Vanacker is funded by the FWO-Flanders (Fund for Scientific Research, Flanders). This work was supported in part by the Concerted Research Initiative of the University of Ghent (Project no. GOA 98-6) and by the FWO-Flanders (Project no. 3G006298).
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·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.
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