Pegylated feline granulocyte colony-stimulating factor increases neutrophil levels in cats

Vet J. 2014 Apr;200(1):44-50. doi: 10.1016/j.tvjl.2014.01.019. Epub 2014 Feb 5.


Neutropenia can often be corrected by treatment with granulocyte-colony stimulating factor (G-CSF) and off-label use of commercial human G-CSF (HuG-CSF) is a commonly used treatment for neutropenic animals. However, long-term HuG-CSF treatment can be associated with adverse effects, including neutropenia. Here, feline (Fe) G-CSF was produced in Pichia pastoris, pegylated (Peg) FeG-CSF and tested in cats. A randomized controlled clinical trial was conducted to evaluate the efficacy of PegFeG-CSF compared to FeG-CSF or HuG-CSF in FIV-infected (n=14), FIV-uninfected healthy cats (n=19), and in HuG-CSF-induced neutropenic cats (n=4). Daily FeG-CSF doses induced higher neutrophil production than HuG-CSF after the second week of treatment (P ⩽ 0.002). Weekly doses of PegFeG-CSF induced higher neutrophil counts and showed greater sustained activity than weekly doses of FeG-CSF. PegFeG-CSF provided the most therapeutic and sustainable neutrophil production (P<0.001) in both FIV-uninfected and FIV-infected cats, without the development of neutralizing antibodies. Conversely, all HuG-CSF-treated cats developed neutralizing antibodies, suggesting cross-reactive antibodies to endogenous G-CSF in a majority of the cases with severe neutropenia. Strikingly, when PegFeG-CSF was used to rescue cats with HuG-CSF-induced neutropenia, clinically normal neutrophil numbers returned. Thus, PegFeG-CSF appears to be a superior treatment for neutropenia in feline patients.

Keywords: Feline neutrophil; G-CSF; Neutralizing antibodies; Neutropenia; Pegylation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Cats
  • Female
  • Granulocyte Colony-Stimulating Factor / immunology*
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Immunodeficiency Virus, Feline / drug effects
  • Immunodeficiency Virus, Feline / immunology*
  • Lentivirus Infections / drug therapy*
  • Lentivirus Infections / immunology
  • Male
  • Neutropenia / chemically induced
  • Neutropenia / metabolism
  • Neutrophils / virology
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Specific Pathogen-Free Organisms


  • Antibodies, Neutralizing
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Polyethylene Glycols
  • pegylated granulocyte colony-stimulating factor