Differential Effects of Short- and Long-term Treatment with Mepolizumab on Eosinophil Kinetics in Blood and Sputum in Eosinophilic Asthma

Overview

Journal iScience

Publisher Cell Press

Date 2021 Aug 19

PMID 34409272

Citations 8

Authors

Marwan Hassani

Tamar Tak

Corneli van Aalst

Saar van Nederveen

Kiki Tesselaar

Nienke Vrisekoop

Leo Koenderman

Affiliations

Soon will be listed here.

Abstract

Mepolizumab (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-H-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 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.

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