Although CSs (corticosteroids) demonstrate potent effects in the control of airway inflammation in asthma, many patients continue to experience symptoms and AHR (airway hyper-responsiveness) despite optimal treatment with these agents, probably due to progressive airway remodelling. Identifying novel therapies that can target airway remodelling and/or airway reactivity may improve symptom control in these patients. We have demonstrated previously that the anti-fibrotic hormone RLN (relaxin) can reverse airway remodelling (epithelial thickening and subepithelial fibrosis) and AHR in a murine model of AAD (allergic airways disease). In the present study, we compared the effects of RLN with a CS (methylprednisolone) on airway remodelling and AHR when administered independently or in combination in the mouse AAD model. Female mice at 6–8 weeks of age were sensitized and challenged to OVA (ovalbumin) over a 9-week period and treated with methylprednisolone, RLN, a combination of both treatments or vehicle controls. Methylprednisolone was administered intraperitoneally on the same day as nebulization for 6 weeks, whereas recombinant human RLN-2 was administered via subcutaneously implanted osmotic mini-pumps from weeks 9–11. RLN or methylprednisolone alone were both able to significantly decrease subepithelial thickness and total lung collagen deposition; whereas RLN but not methylprednisolone significantly decreased epithelial thickness and AHR. Additionally, combination therapy with CS and RLN more effectively reduced subepithelial collagen thickness than either therapy alone. These findings demonstrate that RLN can modulate a broader range of airway remodelling changes and AHR than methylprednisolone and the combination of both treatments offers enhanced control of subepithelial fibrosis.
Skip Nav Destination
Article navigation
Research Article|
September 07 2012
Combination therapy with relaxin and methylprednisolone augments the effects of either treatment alone in inhibiting subepithelial fibrosis in an experimental model of allergic airways disease
Simon G. Royce;
Simon G. Royce
*Department of Allergy and Immune Disorders, Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia
Search for other works by this author on:
Amelia Sedjahtera;
Amelia Sedjahtera
*Department of Allergy and Immune Disorders, Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia
Search for other works by this author on:
Chrishan S. Samuel;
Chrishan S. Samuel
†Howard Florey Institute, Parkville, Victoria 3052, Australia
‡Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3010, Australia
§Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia
Search for other works by this author on:
Mimi L. K. Tang
*Department of Allergy and Immune Disorders, Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia
∥Department of Allergy and Immunology, The Royal Children's Hospital, Parkville, Victoria 3052, Australia
¶Department of Paediatrics, University of Melbourne, Parkville, Victoria 3010, Australia
Associate Professor Mimi L.K. Tang (email mimi.tang@rch.org.au).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 12 2012
Revision Received:
July 20 2012
Accepted:
July 20 2012
Accepted Manuscript online:
July 20 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 124 (1): 41–51.
Article history
Received:
January 12 2012
Revision Received:
July 20 2012
Accepted:
July 20 2012
Accepted Manuscript online:
July 20 2012
Citation
Simon G. Royce, Amelia Sedjahtera, Chrishan S. Samuel, Mimi L. K. Tang; Combination therapy with relaxin and methylprednisolone augments the effects of either treatment alone in inhibiting subepithelial fibrosis in an experimental model of allergic airways disease. Clin Sci (Lond) 1 January 2013; 124 (1): 41–51. doi: https://doi.org/10.1042/CS20120024
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.