Background: Infection is a major clinical complication of orthopaedic implants and prosthetic devices, and patients with traumatic open fractures have a high risk of infection that may exceed 30%. Surgical trauma, burns, and major injuries such as traumatic open fractures induce immunosuppression, decrease resistance to infection, and decrease production of T helper type 1 (Th1) cytokines.
Questions/hypotheses: Exogenous interleukin-12 p70 (IL-12p70 or IL-12), a natural cytokine that plays a central role in Th1 response and bridges innate and adaptive immunities, will reduce open fracture-associated infection.
Method of study: We propose using exogenous IL-12 nanocoating to restore or enhance the body's natural defense system to combat pathogens. Rats will have a femur fractured, inoculated with Staphylococcus aureus or injected with phosphate buffered saline, left open for 1 hour, and then fixed with an intramedullary Kirschner wire with or without IL-12 nanocoating. Animals will be euthanized at postoperative Day 21; samples of blood, soft tissue, bone, and draining lymph nodes will be collected. Infection, bone healing, and local and systemic responses will be determined.
Significance: IL-12 nanocoating is a promising prophylactic means to modulate the host immune response to help prevent open fracture-associated infections and to avoid the problem of antibiotic resistance.