Kinetics of serum granulocyte-colony stimulating factor (G-CSF) concentration and G-CSF receptor expression during G-CSF treatment of cyclophosphamide-treated mice

Goro Matsuzaki, Xiao Yan Li, Yukiko Ohyama, Kikuo Nomoto

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Abstract

We analyzed the kinetics of leukocyte number, serum granulocyte colony stimulating factor (G-CSF) concentration, and G-CSF receptor expression in mice after recombinant human (rh) G-CSF treatment. Intraperitoneal (i.p.) injection with 200 mg/kg of cyclophosphamide (CP) induced a transient decrease of leukocyte number in peripheral blood and spleen. Daily i.p. inoculation of a low dose of rhG-CSF (μg/kg/day) from day 1 of CP injection for 8 days resulted in a significant increase of spleen cell number from day 5 to day 8, while serum rhG-CSF concentration decreased to an undetectable level on day 7. Furthermore, daily i.p. inoculation of high dose rhG-CSF (100 μg/kg/day) for 5 days to CP-injected mice induced a significant increase of leukocytes from day 3 to day 6 in both peripheral blood and spleen, and the increase was higher than that observed after low dose G-CSF treatment. In the course of the high dose rhG-CSF treatment, however, serum rhG-CSF concentration decreased from day 3, which is earlier than that decrease of serum rhG-CSF seen after low dose rhG-CSF treatment. A reverse transcription-polymerase reaction analysis of mRNA expression showed that spleen cells from high dose rhG-CSF-treated mice on day 4 and day 6 expressed more than 10 times higher levels of membrane G-CSF receptors than did those obtained before rhG-CSF treatment. All these results suggest that decrease of serum G-CSF during dairy G-CSF treatment does not always indicate neutralization of G-CSF, but implies that the inoculated G-CSF is still stimulating granulocytes and their precursors by binding to membrane G-CSF receptors which are up-regulated by G-CSF treatment. This observation is important when we measure pharmacokinetics of G-CSF in patients chronically injected with G-CSF.

Original languageEnglish
Pages (from-to)363-369
Number of pages7
JournalInternational Journal of Immunopharmacology
Volume18
Issue number6-7
DOIs
Publication statusPublished - Jun 1 1996

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Granulocyte Colony-Stimulating Factor Receptors
Granulocyte Colony-Stimulating Factor
Cyclophosphamide
Serum
Spleen
Therapeutics
Leukocyte Count
Membranes
Intraperitoneal Injections
Granulocytes
Reverse Transcription
Leukocytes
Pharmacokinetics
Cell Count

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology

Cite this

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title = "Kinetics of serum granulocyte-colony stimulating factor (G-CSF) concentration and G-CSF receptor expression during G-CSF treatment of cyclophosphamide-treated mice",
abstract = "We analyzed the kinetics of leukocyte number, serum granulocyte colony stimulating factor (G-CSF) concentration, and G-CSF receptor expression in mice after recombinant human (rh) G-CSF treatment. Intraperitoneal (i.p.) injection with 200 mg/kg of cyclophosphamide (CP) induced a transient decrease of leukocyte number in peripheral blood and spleen. Daily i.p. inoculation of a low dose of rhG-CSF (μg/kg/day) from day 1 of CP injection for 8 days resulted in a significant increase of spleen cell number from day 5 to day 8, while serum rhG-CSF concentration decreased to an undetectable level on day 7. Furthermore, daily i.p. inoculation of high dose rhG-CSF (100 μg/kg/day) for 5 days to CP-injected mice induced a significant increase of leukocytes from day 3 to day 6 in both peripheral blood and spleen, and the increase was higher than that observed after low dose G-CSF treatment. In the course of the high dose rhG-CSF treatment, however, serum rhG-CSF concentration decreased from day 3, which is earlier than that decrease of serum rhG-CSF seen after low dose rhG-CSF treatment. A reverse transcription-polymerase reaction analysis of mRNA expression showed that spleen cells from high dose rhG-CSF-treated mice on day 4 and day 6 expressed more than 10 times higher levels of membrane G-CSF receptors than did those obtained before rhG-CSF treatment. All these results suggest that decrease of serum G-CSF during dairy G-CSF treatment does not always indicate neutralization of G-CSF, but implies that the inoculated G-CSF is still stimulating granulocytes and their precursors by binding to membrane G-CSF receptors which are up-regulated by G-CSF treatment. This observation is important when we measure pharmacokinetics of G-CSF in patients chronically injected with G-CSF.",
author = "Goro Matsuzaki and Li, {Xiao Yan} and Yukiko Ohyama and Kikuo Nomoto",
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T1 - Kinetics of serum granulocyte-colony stimulating factor (G-CSF) concentration and G-CSF receptor expression during G-CSF treatment of cyclophosphamide-treated mice

AU - Matsuzaki, Goro

AU - Li, Xiao Yan

AU - Ohyama, Yukiko

AU - Nomoto, Kikuo

PY - 1996/6/1

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N2 - We analyzed the kinetics of leukocyte number, serum granulocyte colony stimulating factor (G-CSF) concentration, and G-CSF receptor expression in mice after recombinant human (rh) G-CSF treatment. Intraperitoneal (i.p.) injection with 200 mg/kg of cyclophosphamide (CP) induced a transient decrease of leukocyte number in peripheral blood and spleen. Daily i.p. inoculation of a low dose of rhG-CSF (μg/kg/day) from day 1 of CP injection for 8 days resulted in a significant increase of spleen cell number from day 5 to day 8, while serum rhG-CSF concentration decreased to an undetectable level on day 7. Furthermore, daily i.p. inoculation of high dose rhG-CSF (100 μg/kg/day) for 5 days to CP-injected mice induced a significant increase of leukocytes from day 3 to day 6 in both peripheral blood and spleen, and the increase was higher than that observed after low dose G-CSF treatment. In the course of the high dose rhG-CSF treatment, however, serum rhG-CSF concentration decreased from day 3, which is earlier than that decrease of serum rhG-CSF seen after low dose rhG-CSF treatment. A reverse transcription-polymerase reaction analysis of mRNA expression showed that spleen cells from high dose rhG-CSF-treated mice on day 4 and day 6 expressed more than 10 times higher levels of membrane G-CSF receptors than did those obtained before rhG-CSF treatment. All these results suggest that decrease of serum G-CSF during dairy G-CSF treatment does not always indicate neutralization of G-CSF, but implies that the inoculated G-CSF is still stimulating granulocytes and their precursors by binding to membrane G-CSF receptors which are up-regulated by G-CSF treatment. This observation is important when we measure pharmacokinetics of G-CSF in patients chronically injected with G-CSF.

AB - We analyzed the kinetics of leukocyte number, serum granulocyte colony stimulating factor (G-CSF) concentration, and G-CSF receptor expression in mice after recombinant human (rh) G-CSF treatment. Intraperitoneal (i.p.) injection with 200 mg/kg of cyclophosphamide (CP) induced a transient decrease of leukocyte number in peripheral blood and spleen. Daily i.p. inoculation of a low dose of rhG-CSF (μg/kg/day) from day 1 of CP injection for 8 days resulted in a significant increase of spleen cell number from day 5 to day 8, while serum rhG-CSF concentration decreased to an undetectable level on day 7. Furthermore, daily i.p. inoculation of high dose rhG-CSF (100 μg/kg/day) for 5 days to CP-injected mice induced a significant increase of leukocytes from day 3 to day 6 in both peripheral blood and spleen, and the increase was higher than that observed after low dose G-CSF treatment. In the course of the high dose rhG-CSF treatment, however, serum rhG-CSF concentration decreased from day 3, which is earlier than that decrease of serum rhG-CSF seen after low dose rhG-CSF treatment. A reverse transcription-polymerase reaction analysis of mRNA expression showed that spleen cells from high dose rhG-CSF-treated mice on day 4 and day 6 expressed more than 10 times higher levels of membrane G-CSF receptors than did those obtained before rhG-CSF treatment. All these results suggest that decrease of serum G-CSF during dairy G-CSF treatment does not always indicate neutralization of G-CSF, but implies that the inoculated G-CSF is still stimulating granulocytes and their precursors by binding to membrane G-CSF receptors which are up-regulated by G-CSF treatment. This observation is important when we measure pharmacokinetics of G-CSF in patients chronically injected with G-CSF.

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