Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor

J Clin Invest. 1991 Feb;87(2):704-10. doi: 10.1172/JCI115049.


Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10 micrograms/kg/day for 30 d, which caused an initial neutrophilia, followed by a prolonged period of chronic neutropenia. A control dog treated with recombinant canine G-CSF (rcG-CSF) showed persistent neutrophilia over 3 mo. Serum from dogs during neutropenia contained an antibody to rhG-CSF, which neutralized the stimulatory effects of both rhG-CSF and rcG-CSF on dog marrow neutrophilic progenitor cell growth and on NFS-60 cell proliferation. 4 mo after discontinuation of rhG-CSF, the dogs' neutrophil counts returned to the normal range. Rechallenge with the rhG-CSF re-induced severe neutropenia in 1 wk. Neutropenia was transferred by plasma infusion from a neutropenic dog to a previously normal dog. These data suggest that human rhG-CSF immunizes normal dogs and thereby induces neutralization of endogenous canine G-CSF and neutropenia. This model system should allow more precise definition of the in vivo role of G-CSF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Cell Count
  • Blood Transfusion
  • Chronic Disease
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Granulocyte Colony-Stimulating Factor / immunology
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Humans
  • Immunoglobulin G / immunology
  • Neutropenia / chemically induced*
  • Radioimmunoassay
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Stem Cells


  • Immunoglobulin G
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor