Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma

Marwan Hassani,Tamar Tak,Corneli Van Aalst,Saar Van Nederveen,Kiki Tesselaar,Nienke Vrisekoop,Leo Koenderman

doi:10.1016/j.isci.2021.102913

Marwan Hassani, Tamar Tak + Show 5 more

Open Access

https://doi.org/10.1016/j.isci.2021.102913

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Journal: iScience	Publication Date: Jul 28, 2021
Citations: 12	License type: cc-by

Affiliation: University Medical Center Utrecht, Haga Hospital

Abstract

SummaryMepolizumab (anti-IL-5) is a successful biological for treatment of T2/eosinophilic asthma by blocking the IL-5-eosinophil axis. The kinetics of human eosinophils in blood and sputum was determined to better understand the underlying mechanism(s). Pulse-chase labeling was performed with 6,6-2H2-glucose in patients with asthma after short term (4 days) and long term (84 days) treatment with mepolizumab (n = 10) or placebo (n = 10). The retention time of eosinophils in sputum was longer than in blood. Treatment with mepolizumab induced a fast and long-lasting eosinopenia with no reduction of eosinophil progenitors. The retention time of eosinophils in blood was delayed only after short-term treatment. This leads to the hypothesis that IL-5 increases the number of IL-5-responsive progenitors and potentiates homing to the tissues, leading to reactive eosinophilia. Long-term treatment is associated with low numbers of IL-5-independent eosinophils in blood and tissues. Therefore, long-term treatment with mepolizumab restores the kinetics of eosinophils as normally found in homeostasis.

Highlights

Asthma is a chronic respiratory disease characterized by bronchial inflammation leading to reversible airways obstruction and airway hyperresponsiveness
This is true for Eosinophilic asthma (EA), as IL-5-targeted therapy proved to be only efficacious in asthma characterized by eosinophilic inflammation (Haldar et al, 2009)
Basophil numbers in the circulation did not show a significant difference in numbers between the mepolizumab and placebo groups (Figure 2B) despite the fact these cells express functional IL-5 receptors (Hassani and Koenderman, 2018)

Summary

Introduction

Asthma is a chronic respiratory disease characterized by bronchial inflammation leading to reversible airways obstruction and airway hyperresponsiveness. The disease is characterized by episodes of progressive shortness of breath, cough, wheezing, and chest tightness (Bousquet et al, 2010) It is a very common disorder affecting around 300 million individuals of all ages worldwide (To et al, 2012). Asthma is no longer considered as a single entity but rather as a disease with multiple endotypes (Haldar et al, 2008) It can, for example, be classified as atopic or nonatopic, based on the presence or absence of specific IgE to inhaled allergens, respectively (Vijverberg et al, 2013).

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