Therapeutic administration of Budesonide ameliorates allergen-induced airway remodelling

• Published in: Clinical and experimental allergy 2005-03, Vol.35 (3), p.388-396
• Main Authors: McMillan, S. J., Xanthou, G., Lloyd, C. M.
• Format: Article
• Language: English
• Subjects: Allergens - administration & dosage; Allergic diseases; allergy; Animals; Anti-Asthmatic Agents - therapeutic use; asthma; Asthma - drug therapy; Asthma - immunology; Asthma - metabolism; Biological and medical sciences; Bronchi - immunology; Bronchi - metabolism; Bronchi - pathology; Bronchial Hyperreactivity - drug therapy; Bronchoalveolar Lavage Fluid - immunology; Budesonide - therapeutic use; Chemokine CCL11; Chemokines, CC - immunology; Collagen - metabolism; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Image Processing, Computer-Assisted; Immunopathology; Interleukin-13 - immunology; Interleukin-4 - immunology; Lymphocyte Activation - drug effects; Medical sciences; Mice; Mice, Inbred BALB C; Models, Animal; Mucus; remodelling; Signal Transduction - drug effects; steroids; TGF-β signalling; Time Factors; Transforming Growth Factor beta - metabolism
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.02193.x

Summary Background Airway inflammation and remodelling are important pathophysiologic features of chronic asthma. Although current steroid use demonstrates anti‐inflammatory activity, there are limited effects on the structural changes in the lung tissue. Objective We have used a mouse model of prolonged allergen challenge that exhibits many of the salient features of airway remodelling in order to investigate the anti‐remodelling effects of Budesonide. Methods Treatment was administered therapeutically, with dosing starting after the onset of established eosinophilic airway inflammation and hyper‐reactivity. Results Budesonide administration reduced airway hyper‐reactivity and leukocyte infiltration in association with a decrease in production of the Th2 mediators, IL‐4, IL‐13 and eotaxin‐1. A reduction in peribronchiolar collagen deposition and mucus production was observed. Moreover, our data show for the first time that, Budesonide treatment regulated active transforming growth factor (TGF)‐β signalling with a reduction in the expression of pSmad 2 and the concomitant up‐regulation of Smad 7 in lung tissue sections. Conclusions Therefore, we have determined that administration of Budesonide modulates the progression of airway remodelling following prolonged allergen challenge via regulation of inflammation and active TGF‐β signalling.