Rapid Mobilization of Hematopoietic Progenitor Cells in Rhesus Monkeys by a Single Intravenous Injection of Interleukin-8

• Published in: Blood Vol. 87; no. 2; pp. 781 - 788
• Main Authors: Laterveer, L., Lindley, I.J.D., Heemskerk, D.P.M., Camps, J.A.J., Pauwels, E.K.J., Willemze, R., Fibbe, W.E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.01.1996
• Subjects: Animals; Blood Cell Count - drug effects; Bone Marrow - drug effects; Bone Marrow Cells; Colony-Forming Units Assay; Female; Half-Life; Hematopoietic Stem Cells - drug effects; Humans; Injections, Intravenous; Interleukin-8 - administration & dosage; Interleukin-8 - pharmacokinetics; Interleukin-8 - pharmacology; Macaca mulatta; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - pharmacology; Reproducibility of Results; Time Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.2.781.bloodjournal872781

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 fig/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 μg IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 μg/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 μg 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.