Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor.
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.
Hammond
W P
WP
Department of Medicine, University of Washington School of Medicine, Seattle 98195.
Csiba
E
E
Canin
A
A
Hockman
H
H
Souza
L M
LM
Layton
J E
JE
Dale
D C
DC
D000818:Animals; D001772:Blood Cell Count; D001803:Blood Transfusion; D002908:Chronic Disease; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009503:Neutropenia / Q000139:chemically induced*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D013234:Stem Cells
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor