O27 – Wound Infection after Attenuating a Key Inflammatory Signaling Pathway
Author(s):
Background: Several investigators have proposed attenuating the innate immune response to injury to reduce the risk of subsequent systemic inflammatory response syndrome and organ failure. However, interfering with the innate immune response may increase the risk of subsequent infectious complication, such as wound infections. We have previously demonstrated that topical burn-wound inhibition of a key inflammatory signaling pathway, p38 MAPK, improved end-organ function and mortality in a rodent thermal injury model.
Hypothesis: We hypothesized that while p38 MAPK inhibition significantly attenuates wound innate immune response, it does not increase the risk of subsequent wound infections.
Methods: We used the female red Duroc pig wound model, which has been validated by us and others as a good model of human wound healing with a similar scarring phenotype. We performed three separate experiments with total of 12 pigs. Six pigs received dermatome wound injuries, and 6 received scald burn injuries. Each pig in the dermatome group received ten 4x5cm deep dermal wounds in the dorsal paraspinal region. The pigs with burn injuries received deep partial thickness thermal injury in the paraspinal region using a hot water bottle technique. Out of the total of 12 pigs, 5 were treated with a topical p38 MAPK inhibitor and 7 were in the control group (5 with topical vehicle and 2 with no wound treatment). All the wounds were created after clipping the hair and scrubbing with Chlorhexidine. The pigs did not receive any antibiotics or dressing. The experiments lasted up to 20 weeks after injury.
Results: The topical p38 MAPK inhibition significantly attenuated wound innate immune response with improved healing. All pigs survived until the conclusion of the experiments with normal weight gain. The only wound infection was at a routine biopsy site in a pig that received the vehicle and was successfully treated with one dose of IM antibiotic. One pig had mild eye infection after corneal abrasion during general anesthesia, which was treated with eye drops. There were no other infectious complications.
Conclusions: Topical p38 MAPK inhibition significantly attenuated wound innate immune response; however, none of the wounds treated with the inhibitor developed an infection. Using a porcine model, which closely resembles human wound healing, we demonstrated no infectious complication associated with inhibition of a key inflammatory signaling pathway.