SAT-006 Dihydrotestosterone (DHT) Enhances Major Burn Injury Wound Healing by Regulating the Inflammatory Response in Mice

Abstract

Androgen analogy (Oxandrolone) have been reported to better maintain lean body mass, with improved hypermetabolic responses and shortened healing time for major burn injured patients. This is contradictory to that androgens inhibit local wound repair in men and male mice. The aim of this study therefore is to identify the role of pure androgen dihydrotesterone (DHT) in complex major burn injury, in particularly whether androgen targets local healing process or systemic burn induced hypermetabolism. A DHT silastic tube was subcutaneously implanted to male Balb/c mice prior to surgery as the treatment group. A 2 X 2 cm2 full thickness contact burn wound was created on the dorsal skin of wild type littermates (control) or DHT treated mice. Wound healing rate and body weight changes were measured and compared between treatment and non-treatment group. The serum level of inflammatory cytokine/chemokine was measured using a Multiplex Immunoassay System. Spleen immune cells enumeration was analysis by flow cytometry. Inflammation, re-epithelialization, cell proliferation and collagen deposition was analysed using histology, immunohistochemistry and RT-PCR. In the present study, we found DHT treatment better maintained the body weight in mice and significantly promoted wound healing over 14 days, whereas DHT treatment had no effect on burn-induced hypermetabolism. In control group, major burn injury triggered an acute systematic inflammation response, resulting in significant increased weight of spleen, excess infiltration of nucleated erythroid cells in red pulps of spleen and a significant increase in number of splenic monocytes over 21 days. DHT treatment shortened the systemic inflammation response, evidenced via reduced splenic weight and the number of monocytes in spleen and circulation at day 14 and 21. This finding is further confirmed by less infiltration of macrophages in wound area at day 14 and 21 compared to control group. Taken together, our results suggesting the DHT treatment significantly improve wound healing by accelerated turnover of inflammation response but not through the metabolism. Further studies are necessary to define the exact mechanisms and DHT treatment could be a new therapeutic approach to improve the survivability of major burn injured patient.