Chronic neutropenia : a new canine model induced by human granulocyte colony-stimulating factor

• Published in: The Journal of clinical investigation 1991-02, Vol.87 (2), p.704-710
• Main Authors: HAMMOND, W. P, CSIBA, E, CANIN, A, HOCKMAN, H, SOUZA, L. M, LAYTON, J. E, DALE, D. C
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Cell Count; Blood Transfusion; Chronic Disease; Dogs; Enzyme-Linked Immunosorbent Assay; Granulocyte Colony-Stimulating Factor - immunology; Granulocyte Colony-Stimulating Factor - pharmacology; Hematologic and hematopoietic diseases; Humans; Immunoglobulin G - immunology; Medical sciences; Neutropenia - chemically induced; Radioimmunoassay; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Stem Cells
• ISSN: 0021-9738; 1558-8238
• 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.