The Role of IL-5 in airway remodelling in severe asthma

Asthma is a common chronic lung inflammatory disease reported to affect both pediatrics and adults with a significant morbidity, mortality, and financial burden worldwide. The main concern with asthma is the irreversible tissue remodeling of the airway due to the chronic inflammatory environment that will eventually disrupt the whole structure of the airway. Most of the advanced asthmatic cases are being treated with steroids but the challenge remains the development of steroid resistance which will extremely limit the treatment options of the patient toward biological therapy. Interleukin 5 is recently being a hot biological target that will ameliorate the tissue remodeling process when neutralized with a monoclonal Antibody (Mepolizumab) that will reduce the rate of eosinophilia, while our recent studies characterize the expression of IL-5R on lung derived fibroblast that could be a new target of Mepolizumab, our preliminary results showed that stimulation of fibroblasts with rIL-5 leading to an increase release of several Matrix Metalloproteinases and Extracellular matrix proteins such as collagen and Fibronectin that is suggested to contribute strongly in tissue remodeling process but whether Anti-IL-5 (Mepolizumab) have the capacity to reduce fibrosis and counteract the fibrotic effect of rIL-5 is yet to be investigated. So, this proposal aims to investigate the direct potential role of rIL-5 in fibrosis and the antagonistic effect of Anti-IL-5 in-vitro using human derived fibroblasts from both asthmatic and Normal donors.