Published ahead of print on October 24, 2002, doi:10.1164/rccm.200205-455OC Am. J. Respir. Crit. Care Med., Volume 167, Number 2, January 2003, 193-198 A more recent version of this article appeared on January 15, 2003
Submitted on May 25, 2002 In vivo and in vitro effects of SAR 943, a rapamycin analogue, on airway inflammation and remodelingFujitani Yasushi1 and Alexandre Trifilieff1*1 Novartis Respiratory Research Centre, Horsham, United Kingdom * To whom correspondence should be addressed. E-mail: alexandre.trifilieff{at}pharma.novartis.com.
No current therapy is considered to be satisfactory for severe asthma and alternative approaches are still required for what is a major unmet medical need. In this study we compared the effect of a rapamycin derivative, SAR 943 with budesonide, using a murine model of lung inflammation and remodeling. Allergen challenge of ovalbumin sensitised BALB/c mice induced an increase in the levels of IL-5 and IL-4; numbers of eosinophil, neutrophil and lymphocyte; cellular fibronectin; lung epithelial cell proliferation and mucus hypersecretory phenotype as well as hyperreactivity to methacholine. Both SAR 943 and budesonide, when given intranasally an hour before and 24 hours after the aerosol challenge inhibited all these parameters with similar potency (ED50 of 1 mg/kg). In primary cultured smooth muscle cells from human airways, SAR 943 dose-dependently inhibited EGF-induced proliferation but did not affect the basal cell proliferation. Neither the basal or stimulated proliferation of a human bronchial epithelial cell line (16HBE14o-) was affected by SAR 943. In conclusion, SAR 943 is as effective as budesonide in inhibiting both lung inflammation and remodelling in a murine model of asthma. Hence, this class of compound could offer beneficial effects in patients with severe asthma. Key words: Mice, Inflammation, Remodelling, Immunosuppresant
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
