Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma
Summary: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221008816 |
| _version_ | 1831770010989625344 |
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| author | Marwan Hassani Tamar Tak Corneli van Aalst Saar van Nederveen Kiki Tesselaar Nienke Vrisekoop Leo Koenderman |
| author_facet | Marwan Hassani Tamar Tak Corneli van Aalst Saar van Nederveen Kiki Tesselaar Nienke Vrisekoop Leo Koenderman |
| author_sort | Marwan Hassani |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-22T07:32:30Z |
| format | Article |
| id | doaj.art-7dfa904d5d90400fa313594d0d4b5ef0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-22T07:32:30Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-7dfa904d5d90400fa313594d0d4b5ef02022-12-21T18:33:59ZengElsevieriScience2589-00422021-08-01248102913Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthmaMarwan Hassani0Tamar Tak1Corneli van Aalst2Saar van Nederveen3Kiki Tesselaar4Nienke Vrisekoop5Leo Koenderman6Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands; Department of Respiratory Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands; Department of Respiratory Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands; Department of Respiratory Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The NetherlandsDepartment of Respiratory Medicine, HAGA Hospital, 2545AA The Hague, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands; Department of Respiratory Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands; Department of Respiratory Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221008816Health sciencesImmunologyRespiratory medicineClinical medicineDrugs |
| spellingShingle | Marwan Hassani Tamar Tak Corneli van Aalst Saar van Nederveen Kiki Tesselaar Nienke Vrisekoop Leo Koenderman Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma iScience Health sciences Immunology Respiratory medicine Clinical medicine Drugs |
| title | Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma |
| title_full | Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma |
| title_fullStr | Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma |
| title_full_unstemmed | Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma |
| title_short | Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma |
| title_sort | differential effects of short and long term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma |
| topic | Health sciences Immunology Respiratory medicine Clinical medicine Drugs |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221008816 |
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