title: Porcine granulocyte-colony stimulating factor (G-CSF) delivered via replication-defective adenovirus induces a sustained increase in circulating peripheral blood neutrophils.
abstract: The use of immunomodulators is a promising area for biotherapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease. Cytokines, including granulocyte-colony stimulating factor (G-CSF), have been investigated for potential value as biotherapeutic proteins. G-CSF enhances the production and release of neutrophils from bone marrow and is already licensed for use in humans. A limitation of cytokines as immunomodulators is their short half-life which may limit their usefulness as a one-time injectable in production-animal medicine. Here we report that administration of recombinant G-CSF induced a transient neutrophilia in pigs; however, delivery of porcine G-CSF encoded in a replication-defective adenovirus (Ad5) vector significantly increased the neutrophilia pharmacodynamics effect. Pigs given one injection of the Ad5-G-CSF had a neutrophilia that peaked between days 3-11 post-treatment and neutrophil counts remained elevated for more than 2 weeks. Neutrophils from Ad5-G-CSF treated pigs were fully functional based on their ability to release neutrophil extracellular traps and oxidative metabolism after in vitro stimulation. Since acceptable alternatives to the use of antibiotics in food-animal production need to be explored, we provide evidence for G-CSF as a possible candidate for agents in which neutrophils can provide protection.
authors.affiliation: Virus and Prion Diseases Unit, National Animal Disease Center, Agricultural Research Service, USDA, PO Box 70, Ames, IA 50010, USA. Electronic address: crystal.loving@ars.usda.gov.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Loving
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kehrli
authors.forename: Susan L
authors.initials: SL
authors.lastname: Brockmeier
authors.forename: Darrell O
authors.initials: DO
authors.lastname: Bayles
authors.forename: David D
authors.initials: DD
authors.lastname: Michael
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Schlink
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Lager
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003673:Defective Viruses / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013997:Time Factors; D014779:Virus Replication
chemical_list: D050505:Mutant Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor
keywords: Adenovirus gene delivery; Alternatives to antibiotics; G-CSF; Neutrophilia; Neutrophils; Porcine