title: Additive effects of exogenous IL-12 supplementation and antibiotic treatment in infection prophylaxis.
abstract: The increasing clinical incidence and host risk of open fracture-associated infections, as well as the reduced effectiveness of conventional antibiotics to treat such infections, have driven the development of new therapies for the prophylaxis of open fracture-associated infections. We investigated percutaneous supplementation of a natural cytokine (i.e., interleukin 12p70 or IL-12) at an open fracture site to reduce open fracture-associated infections. We also determined the efficacy of the combination therapy of IL-12 and conventional antibiotic therapy in the prophylaxis of open fracture-associated infections. An open femur fracture infection model was produced by direct inoculation of a clinical isolate of Staphylococcus aureus after creating a femur fracture using rats. The animals were assigned to one of four groups: no drug administration, percutaneous supplementation of IL-12, intraperitoneal administration of the antibiotic ampicillin, or percutaneous IL-12 in combination with intraperitoneal ampicillin. Animals were euthanized at postoperative days 6, 10, 14, and 21. Percutaneous IL-12 led to a reduction in infection at postoperative days 6 and 10. For the first time, exogenous IL-12 was found to have additive effects in the prevention of infection when combined with conventional treatment (i.e., antibiotic therapy). Combination therapy of ampicillin and IL-12 substantially reduced the infection rate at postoperative day 6 and also decreased the time needed for complete inhibition of infection. Therefore, exogenous IL-12, providing a mechanism of protection independent of antibiotic resistance, complements the routine use of antibiotics.
authors.affiliation: Biomaterials, Bioengineering & Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, West Virginia 26506, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Boyce
authors.forename: Brock A
authors.initials: BA
authors.lastname: Lindsey
authors.forename: Nina B
authors.initials: NB
authors.lastname: Clovis
authors.forename: E Suzanne
authors.initials: ES
authors.lastname: Smith
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Hobbs
authors.forename: David F
authors.initials: DF
authors.lastname: Hubbard
authors.forename: Sanford E
authors.initials: SE
authors.lastname: Emery
authors.forename: John B
authors.initials: JB
authors.lastname: Barnett
authors.forename: Bingyun
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D019072:Antibiotic Prophylaxis; D001424:Bacterial Infections / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005597:Fractures, Open / Q000150:complications*; D018664:Interleukin-12 / Q000008:administration & dosage*; D008262:Macrophage Activation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss
chemical_list: D018664:Interleukin-12