Abstract
Androgens have been known to inhibit cutaneous wound healing in men and male mice. However, in children with major burn injuries, a synthetic androgen was reported clinically to improve wound healing. The aim of this study is to investigate the role of dihydrotestosterone (DHT) as a new therapeutic approach in treating major burn injury. In the present study, mice received systemic androgen treatment post major burn injury. Wound healing rate and body weight were monitored over 21 days. The serum level of inflammatory cytokines/chemokines were measured using multiplex immunoassays. In addition, splenocyte enumeration was performed by flow cytometry. Healing phases of inflammation, re-epithelialization, cell proliferation and collagen deposition were also examined. In results, DHT treated mice lost less weight and displayed accelerated wound healing but has no impact on hypermetabolism. Mice, after burn injury, displayed acute systemic inflammatory responses over 21 days. DHT treatment shortened the systemic inflammatory response with reduced splenic weight and monocyte numbers on day 14 and 21. DHT treatment also reduced wound infiltrating macrophage numbers. In conclusion, DHT treatment facilitates local wound healing by accelerating the resolution of inflammation, but not through alterations of post-burn hypermetabolic response.
Highlights
Both cutaneous and burn injuries immediately trigger the local wound healing process
The systemic hypermetabolic response refers to a significant increase in the resting energy expenditure, which is largely driven by elevated levels of circulating catecholamines, glucocorticoids and pro-inflammatory cytokines following burn injury [4]
We investigated the effects of DHT on a major burn injury throughout the wound healing process
Summary
Both cutaneous (non-burn) and burn injuries immediately trigger the local wound healing process. Castration of male mice to reduce circulating androgens, accelerates cutaneous wound healing through the attenuation of the local inflammatory response and increased extracellular matrix (ECM) deposition [9,10,11]. Delayed wound healing was reported after chemical blockade of testosterone conversion to DHT or in genetic androgen receptor (AR) knockout mice [9,11,12,13] In these studies, androgens play an inhibitory role in cutaneous wound healing through the increased production of IL-6 and TNF and reduced wound re-epithelialization and collagen deposition [9,11,12,13]. In contrast to the known inhibitory effects of androgens by prolonging inflammation in cutaneous wound healing, clinical studies have reported that testosterone and the synthetic androgen, oxandrolone can enhance recovery from a burn injury. This study aims to investigate DHT treatment as a new therapeutic approach in treating major burn injury
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