title: Pegylated feline granulocyte colony-stimulating factor increases neutrophil levels in cats.
abstract: 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.
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Coleman
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakagawa
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Offner
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Noon-Song
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Coisman
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Roff
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA. Electronic address: yamamoto@ufl.edu.
authors.forename: J K
authors.initials: JK
authors.lastname: Yamamoto
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 11088, Gainesville, FL 32611-0880, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Abbott
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002415:Cats; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects / Q000276:immunology*; D016180:Lentivirus Infections / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced / Q000378:metabolism; D009504:Neutrophils / Q000821:virology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms
chemical_list: D057134:Antibodies, Neutralizing; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; C423652:pegylated granulocyte colony-stimulating factor
keywords: Feline neutrophil; G-CSF; Neutralizing antibodies; Neutropenia; Pegylation