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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 6,6-2H2-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.

Original languageEnglish
Article number102913
Number of pages19
JournaliScience
Volume24
Issue number8
DOIs
Publication statusPublished - 20 Aug 2021

Keywords

  • Clinical medicine
  • Drugs
  • Health sciences
  • Immunology
  • Respiratory medicine

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