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: Brandon M Boyce, Brock A Lindsey, Nina B Clovis, E Suzanne Smith, Gerald R Hobbs, David F Hubbard, Sanford E Emery, John B Barnett, Bingyun Li
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 30 Issue 2 Pg. 196-202 (Feb 2012) ISSN: 1554-527X [Electronic] United States
• PMID: 21815205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Orthopaedic Research Society.

Chemical References

• Interleukin-12

Topics

• Animals
• Antibiotic Prophylaxis
• Bacterial Infections (prevention & control)
• Drug Therapy, Combination
• Fractures, Open (complications)
• Interleukin-12 (administration & dosage)
• Macrophage Activation
• Rats
• Rats, Sprague-Dawley
• Weight Loss