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

Abstract

Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10 gg/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. (J. Clin. Invest. 1991. 87:704-710.) Key words: immunoglobulin * in vitro culture * in vivo treatment

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

“…Dogs depleted of G-CSF by a neutralizing antibody develop profound and selective neutropenia [20], but dogs similarly depleted of GM-CSF do not become neutropenic [21]. Furthermore, disruption of the G-CSF gene in knock-out mice results in chronic neutropenia [22], whereas GM-CSF knock-out mice do not become neutropenic [23].…”

Requirement of Endogenous Stem Cell Factor and Granulocyte-Colony-Stimulating Factor for IL-17-Mediated Granulopoiesis

“…Dale and colleagues. (20) previously reported neutropenia in dogs with the development of neutralizing anti-G-CSF Abs . Similar to their report, over the 7-day experiment, anti-G-CSF administration resulted in mild but statistically significant neutropenia in both AdCMVLuc-treated Sl/ Sld and littermate control animals (Fig.…”

Effects of recombinant granulocyte-colony stimulating factor administration duringMycobacterium aviuminfection in mice

“…Since we used a xenogeneic molecule in the previous experiment, it was possible that an immune response to the molecule might have taken place reducing the effectiveness of the therapy with rHuG-CSF and even leading to cross-reacting effects on the native G-CSF, as shown previously in dogs [27]. We therefore tested in a similar protocol the effects of rMuG-CSF.…”