摘要：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 ofIL-5-responsiveprogenitors 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.Graphical abstractDisplay OmittedHighlights•Anti-IL-5 (mepolizumab) treatment leads to inhibition of reactive eosinophilia•Reactive blood eosinophils have a high retention time in the absence of IL-5•Eosinophils are long lived in the sputum of eosinophil asthmatics•Anti-IL-5 reduces proliferating progenitors rather than inhibiting differentiationHealth sciences; Immunology; Respiratory medicine; Clinical medicine; Drugs
