Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.
ARTICLES|
January 15, 1996
Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8
L Laterveer,
L Laterveer
Department of Hematology, University Hospital Leiden, The Netherlands.
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IJ Lindley,
IJ Lindley
Department of Hematology, University Hospital Leiden, The Netherlands.
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DP Heemskerk,
DP Heemskerk
Department of Hematology, University Hospital Leiden, The Netherlands.
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JA Camps,
JA Camps
Department of Hematology, University Hospital Leiden, The Netherlands.
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EK Pauwels,
EK Pauwels
Department of Hematology, University Hospital Leiden, The Netherlands.
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R Willemze,
R Willemze
Department of Hematology, University Hospital Leiden, The Netherlands.
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WE Fibbe
WE Fibbe
Department of Hematology, University Hospital Leiden, The Netherlands.
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Blood (1996) 87 (2): 781–788.
Citation
L Laterveer, IJ Lindley, DP Heemskerk, JA Camps, EK Pauwels, R Willemze, WE Fibbe; Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8. Blood 1996; 87 (2): 781–788. doi: https://doi.org/10.1182/blood.V87.2.781.bloodjournal872781
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