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.