Dexamethasone promotes granulocyte mobilization by prolonging the half‐life of granulocyte–colony‐stimulating factor in healthy donors for granulocyte transfusions

Hiemstra, Ida H.; Hamme, John L. van; Janssen, M.H.M.; Berg, Timo K. van den; Kuijpers, Taco W.

doi:10.1111/trf.13941

Cited by 9 publications

(7 citation statements)

References 47 publications

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“…Mobilizing a sufficient number of neutrophils is considered crucial for the therapeutic efficacy of GTX. We show that G-CSF was more efficient at mobilizing neutrophils into circulation in all donors than prednisone corroborating a similar observation by Hiemstra et al ( 28 ). Worel et al ( 29 ) also reported that a lower proportion of prednisolone GCs (56%) contained the minimal ANC per GC unit for transfusion ( 29 ).…”

Section: Discussionsupporting

confidence: 93%

Comparison of Neutrophil Function in Granulocyte Concentrates From Prednisone- and G-CSF-Treated Donors: Effect of Stimulant, Leukapheresis and Storage

et al. 2022

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Transfusion of granulocyte concentrates (GC) is an alternative therapy for neutropenic patients with life-threatening infections. While neutrophils are the main source of antimicrobial activity, only neutrophil numbers are used to certify GCs. The objective of this study was thus to functionally characterize neutrophils in GCs prepared by leukapheresis from G-CSF-stimulated donors and compare to the less characterized prednisone GCs. GCs prepared from healthy donors stimulated with prednisone and then G-CSF after a 6-month washout period were analyzed prior to and after leukapheresis, and after storage. Leukocyte composition, neutrophil viability, calcium mobilization, chemotaxis, phagocytosis, reactive oxygen species, cytokine production and metabolites were determined. G-CSF GCs contained significantly more neutrophils than prednisone GCs of which 40% were immature. In comparison to non-stimulated healthy donor neutrophils, prednisone GC neutrophils exhibited enhanced phagocytosis and G-CSF GC neutrophils showed decreased chemotaxis but increased IL-8 production. Leukapheresis altered prednisone GC neutrophil responses. Storage had a significant, negative impact on G-CSF GC neutrophils compared to prednisone GC neutrophils. G-CSF and prednisone GC neutrophils thus differ in maturity and function, and G-CSF GC neutrophils are more sensitive to storage. Functional testing of GC neutrophils and better storage conditions would improve the quality of this blood product.

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Section: Discussionsupporting

confidence: 93%

Comparison of Neutrophil Function in Granulocyte Concentrates From Prednisone- and G-CSF-Treated Donors: Effect of Stimulant, Leukapheresis and Storage

et al. 2022

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“…Rather, the inhibition of the pathogenic effects of such cells may have a beneficial effect on MIRS. For instance, glucocorticoids have been shown to inhibit NET formation [73] and ROS production [74], while enhancing neutrophil mobilization [75], which renders them as good candidates for the reduction of neutrophil-derived damage (Figure 3).…”

Section: Immunoregulation As a Modern Alternative To Immunosuppressionmentioning

confidence: 99%

Ischemia/Reperfusion Injury: Pathophysiology, Current Clinical Management, and Potential Preventive Approaches

Sánchez-Hernández

Torres-Alarcón

González-Cortés

et al. 2020

Mediators of Inflammation

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Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. In such a setting, the establishment of an effective therapy to treat this condition has been elusive, perhaps because the experimental treatments have been conceived to block just one of the many pathogenic pathways of the disease, or because they thwart the tissue-repairing phase of the syndrome. Either way, we think that a discussion about the pathophysiology of the disease and the mechanisms of action of some drugs may shed some clarity on the topic.

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“…Zur Mobilisierung der Granulozyten in den Blutstrom der Spender wird die Gabe von 300-480 µg Granulocyte Colony stimulating Factor (G-CSF) subkutan zusammen mit 8 mg oralem Dexamethason ungefähr 12 h vor Beginn der Apherese empfohlen [15]. Dexamethason verlängert hierbei die Halbwertszeit von G-CSF [20] und führt demnach zu einer höheren Granulozytenausbeute [20,21]. Die Gabe von Medikamenten mit potenziellen Nebenwirkungen an Personen ohne gesundheitliche Indikation ist natürlich nicht ganz unkritisch zu betrachten.…”

Section: Neuere Informationen Zur Spenderstimulationunclassified

Granulozytentransfusion: Update 2020

Doblinger

Gruber

Ahrens

2020

Transfusionsmedizin - Immunhämatologie · Hämotherapie · Transpl

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ZusammenfassungDie therapeutische Anwendung von Granulozytenkonzentraten erfolgt im klinischen Alltag im Gegensatz zu der anderer Blutprodukte nur selten und unregelmäßig. Der zurückhaltende Einsatz beruht unter anderem auf dem Fehlen einer breiten Evidenz, logistischen und wirtschaftlichen Problemen und dem Vorhandensein anderer potenter Therapieoptionen neutropener Infektionen. Dennoch gab es in den letzten Jahren neue wissenschaftliche Erkenntnisse nicht nur zu Physiologie und Pathophysiologie der Granulozyten, wie neu charakterisierten zellulären Verteidigungsstrategien oder deren Mitwirkung bei thrombotischen oder malignen Ereignissen, sondern auch zu deren therapeutischem Effekt. Dieser wird von einer Vielzahl an Parametern, wie der Art der Infektion, dem Transfusionszeitpunkt und der Dosis, beeinflusst. Das macht die Indikationsstellung zu einer komplexen Einzelfallentscheidung und es gilt, die heterogene Datenlage systematisch zusammenzufassen. Außerdem wurden die etablierten Indikationen neutropener bzw. neutropathischer Infektionen um experimentelle, mögliche neue Anwendungsgebiete wie die Mukositis oder Leukämiebehandlung erweitert. Die erfolgreiche Anwendung setzt eine geeignete, moderne Herstellungsweise voraus. Neben der Apherese, bei der eine relativ hohe Spenderbelastung unter anderem durch Nebenwirkungen von Mobilisationsregime und Sedimentationsbeschleunigern berücksichtigt werden muss, existieren weitere Verfahren wie die Gewinnung von Granulozyten aus Buffy Coats von Vollblutspenden. Diese versprechen eine Reduktion logistischer Probleme und unerwünschter Wirkungen auf den Spender. Unerwünschte Wirkungen bei Empfängern von Granulozytentransfusionen sollten nach wie vor berücksichtigt und gegen einen erhofften therapeutischen Effekt abgewogen werden.

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Dexamethasone promotes granulocyte mobilization by prolonging the half‐life of granulocyte–colony‐stimulating factor in healthy donors for granulocyte transfusions

Abstract: Dexamethasone increases granulocyte yield upon coadministration with G-CSF by extending G-CSF half-life. This observation might also be exploited in the coadministration of dexamethasone with other recombinant proteins to modulate their half-life.

Cited by 9 publications

References 47 publications

Comparison of Neutrophil Function in Granulocyte Concentrates From Prednisone- and G-CSF-Treated Donors: Effect of Stimulant, Leukapheresis and Storage

Comparison of Neutrophil Function in Granulocyte Concentrates From Prednisone- and G-CSF-Treated Donors: Effect of Stimulant, Leukapheresis and Storage

Ischemia/Reperfusion Injury: Pathophysiology, Current Clinical Management, and Potential Preventive Approaches

Granulozytentransfusion: Update 2020

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