Abstract
Interleukin-5 (IL-5) exerts a central pathogenic role in differentiation, recruitment, survival, and degranulation of eosinophils. Indeed, during the last years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the powerful actions of IL-5 finalized to the induction, maintenance, and amplification of eosinophilic inflammation. Therefore, IL-5 is a suitable target for add-on biological therapies based on either IL-5 inhibition (mepolizumab, reslizumab) or blockade of its receptor (benralizumab). These modern treatments can result in being definitely beneficial for patients with severe type 2 (T2)-high eosinophilic asthma, refractory to conventional anti-inflammatory drugs such as inhaled and even systemic corticosteroids.
Highlights
Asthma is a chronic and heterogeneous airway disorder, characterized by recurrent respiratory symptoms including wheezing, cough, and chest tightness, which are caused by usually reversible airflow limitation due to bronchial inflammation and remodeling (Holgate et al, 2015; Pelaia et al, 2015)
Many patients with severe asthma express a type 2 (T2)-high phenotype featured by eosinophilic inflammation (Bousquet et al, 1990; Schleich et al, 2014)
T2-high asthma is characterized by accumulation of eosinophils within the airways, where these cells produce and release cytokines, chemokines, growth factors, cytotoxic proteins, and lipid mediators, which together play a relevant role in the pathobiology of bronchial inflammation and remodeling (Bochner and Gleich, 2010)
Summary
Asthma is a chronic and heterogeneous airway disorder, characterized by recurrent respiratory symptoms including wheezing, cough, and chest tightness, which are caused by usually reversible airflow limitation due to bronchial inflammation and remodeling (Holgate et al, 2015; Pelaia et al, 2015). The efficacy of mepolizumab was demonstrated by Nair et al and Haldar et al in a few patients with severe eosinophilic asthma experiencing frequent disease exacerbations (Haldar et al, 2009; Nair et al, 2009), These two seminal studies were the first ones to show that mepolizumab was able to significantly decrease asthma exacerbations, and this effect was concomitant with a sharp reduction of both sputum and blood eosinophils (Haldar et al, 2009; Nair et al, 2009) In addition to such results, using chest CT (computed tomography) scan, Haldar et al documented that mepolizumab decreased both thickness and total area of bronchial walls (Haldar et al, 2009). Preliminary data suggest that in a real-world setting mepolizumab can result in being even more effective than in RCT, and such findings might
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