title: FIV-infected cats respond to short-term rHuG-CSF treatment which results in anti-G-CSF neutralizing antibody production that inactivates drug activity.
abstract: The hematological and virological effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over study were injected subcutaneously with 5 microg/kg of rHuG-CSF daily for 3 weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated cats had significant increases in neutrophil counts that peaked on days 11-21 of treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid ratios of the bone marrow cells without significant changes in lymphocyte, CD4 counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in peripheral blood, and without clinical and hematological toxicities. Five of six rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14-21 days of treatment, which correlated with decreasing neutrophil counts and increasing neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly developed neutralizing antibodies to rHuG-CSF, while one cat also developed neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF treatment increased neutrophil counts in FIV-infected cats without affecting the infection status of cats. However, long-term use of rHuG-CSF is not recommended in cats because of the neutralizing antibody production to rHuG-CSF that affects the drug activity. In addition, a preliminary finding suggests that repeated treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which may potentially affect the homeostasis of endogenous FeG-CSF.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
authors.forename: K
authors.initials: K
authors.lastname: Phillips
authors.forename: M
authors.initials: M
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: R
authors.initials: R
authors.lastname: Raskin
authors.forename: M
authors.initials: M
authors.lastname: Volz
authors.forename: E W
authors.initials: EW
authors.lastname: Uhl
authors.forename: J K
authors.initials: JK
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001853:Bone Marrow / Q000821:virology; D002415:Cats; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects / Q000276:immunology*; D016180:Lentivirus Infections / Q000188:drug therapy* / Q000276:immunology; D009504:Neutrophils / Q000821:virology; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor