Portal de Periódicos da CAPES

Human beta‐defensin‐3 promotes wound healing in infected diabetic wounds

2008; Wiley; Volume: 11; Issue: 3 Linguagem: Inglês

10.1002/jgm.1287

1521-2254

Tobias Hirsch, Malte Spielmann, Baraa Zuhaili, Magdalena Fossum, Marie Oliver Metzig, Till Koehler, Hans‐Ulrich Steinau, Feng Yao, Andrew B. Onderdonk, Lars Steinstraesser, Elof Eriksson,

Immune Response and Inflammation

Abstract Background Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta‐defensin (hBD)‐3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD‐3 expression in a model of infected diabetic wounds. Methods Excisional wounds were created on the backs of Yorkshire pigs and Ad5‐CMV‐hBD‐3 vectors were microseeded. Wounds were inoculated with S. aureus , covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re‐epithelialization, wound contraction, wound fluid production and blood vessel formation. Results hBD‐3‐treated wounds showed a total bacterial load of 2.1 × 10 8 colony‐forming units (CFU)/g tissue, versus 1.3 × 10 9 CFU/g tissue for controls ( p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re‐epithelialization showed 75 ± 15% wound closure for hBD‐3 expressing wounds and 50 ± 16% for controls ( p < 0.01). hBD‐3 expression was in the range 15–20 ng/ml of wound fluid during day 1–4. The lower dose of 2 × 10 9 Ad5‐CMV‐hBD‐3 showed no effect, suggesting a dose dependency for hBD‐3. Conclusions In the present study, we show that hBD‐3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large‐animal model. Furthermore, a ten‐fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta‐defensin‐3 may play a major role in diabetic wound healing and wound infections. Copyright © 2008 John Wiley & Sons, Ltd.