Additive effects of exogenous IL-12 supplementation and antibiotic treatment in infection prophylaxis

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. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:196–202, 2012