Effects of ciclesonide and fluticasone propionate on allergen-induced airway inflammation and remodeling features.
BACKGROUND
Several topical corticosteroids are available as anti-inflammatory treatment for asthma. Their comparative effects on allergic inflammation and airway remodeling are unclear.


OBJECTIVE
We compared the effects of ciclesonide with those of fluticasone propionate in a Brown Norway rat model of chronic allergic asthma.


METHODS
Rats sensitized and exposed to ovalbumin (OVA) were treated with dry powder vehicle, ciclesonide, or fluticasone (0.01, 0.03, and 0.1 mg/kg administered intratracheally) 24 hours and 1 hour before each of 6 OVA exposures. In a second protocol we administered 0.1 mg/kg ciclesonide or fluticasone only after the third OVA exposure.


RESULTS
Ciclesonide at all doses inhibited the allergen-induced increase in airway eosinophils and T cells, reduced goblet cell hyperplasia, and decreased 5-bromo-2'-deoxyuridine-immunoreactive airway smooth muscle (ASM) and epithelial cells. At 0.03 and 0.1 mg/kg ciclesonide, bronchial hyperresponsiveness (BHR) was also inhibited. Fluticasone did not attenuate allergen-induced BHR, despite inhibiting airway eosinophils and T cells, goblet cell hyperplasia, and 5-bromo-2'-deoxyuridine-immunoreactive ASM and epithelial cells. Fluticasone (0.1 mg/kg) caused a significant reduction in body weight (9%) compared with ciclesonide (0.1 mg/kg). Ciclesonide did not change plasma corticosterone levels, whereas fluticasone (0.1 mg/kg) reduced them. In the second protocol both fluticasone and ciclesonide inhibited BHR, bronchial inflammation, goblet cell hyperplasia, and ASM proliferation.


CONCLUSIONS
Ciclesonide potently inhibited chronic allergic inflammation, remodeling, and BHR without having an effect on body weight and the hypothalamic-pituitary-adrenal axis. Fluticasone prevented airway inflammation but not BHR, but both fluticasone and ciclesonide are effective at reversal of BHR, inflammation, and remodeling features.
Leung
Sum Yee
SY
Department of Thoracic Medicine, National Heart & Lung Institute, Imperial College, London, UK.
Eynott
Paul
P
Nath
Puneeta
P
Chung
Kian Fan
KF
D000280:Administration, Inhalation; D000485:Allergens / Q000009:adverse effects; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects; D000068298:Fluticasone; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D010047:Ovalbumin / Q000009:adverse effects; D011282:Pregnenediones / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D000730:Androstadienes; D018926:Anti-Allergic Agents; D011282:Pregnenediones; D010047:Ovalbumin; D000068298:Fluticasone; C120481:ciclesonide; D003345:Corticosterone