title: G-CSF enhances resolution of Staphylococcus aureus wound infection in an age-dependent manner.
abstract: This study tested the hypothesis that heightened bacterial colonization and delayed wound closure in aged mice could be attenuated by granulocyte colony-stimulating factor (G-CSF) treatment. Previously, we reported that aged mice had elevated bacterial levels, protracted wound closure, and reduced wound neutrophil accumulation after Staphylococcus aureus wound infection relative to young mice. In aseptic wound models, G-CSF treatment improved wound closure in aged mice to rates observed in young mice. Given these data, our objective was to determine if G-CSF could restore age-associated differences in wound bacterial burden and closure by increasing wound neutrophil recruitment. Young (3- to 4-month) and aged (18- to 20-month) BALB/c mice received three dorsal subcutaneous injections of G-CSF (250 ng/50 μL per injection) or saline control (50 μL per injection) 30 min after wound infection. Mice were killed at days 3 and 7 after wound infection, and bacterial colonization, wound size, wound leukocyte accumulation, and peripheral blood were evaluated. At days 3 and 7 after wound infection, bacterial colonization was significantly reduced in G-CSF-treated aged mice to levels observed in saline-treated young animals. Wound size was reduced in G-CSF-treated aged animals, with no effect on wound size in G-CSF-treated young mice. Local G-CSF treatment significantly enhanced neutrophil wound accumulation in aged mice, whereas there was no G-CSF-induced change in young mice. These data demonstrate that G-CSF enhances bacterial clearance and wound closure in an age-dependent manner. Moreover, G-CSF may be of therapeutic potential in the setting of postoperative wound infection or chronic nonhealing wounds in elderly patients.
authors.affiliation: *Burn and Shock Trauma Institute, †Cell Biology, Neurobiology and Anatomy Program, ‡Immunology and Aging Program, §Stritch School of Medicine, and ∥Departments of Surgery, and ¶Microbiology and Immunology, Loyola University Chicago-Health Sciences Division, Maywood, Illinois.
authors.forename: Aleah L
authors.initials: AL
authors.lastname: Brubaker
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
mesh_terms: D000375:Aging; D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D012867:Skin / Q000293:injuries; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects*; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor