Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice

• Published in: International journal of molecular sciences Vol. 21; no. 17; p. 6231
• Main Authors: Shi, Huaikai, Lo, Tsun-Ho, Ma, Duncan, Condor, Brenton, Lesmana, Brian, Parungao, Roxanne J, Tsai, Kevin H-Y, Kim, Sarah, Chen, Hsiao-Ting, Silveira, Pablo A, Li, Zhe, Cooper, Mark S, Simanainen, Ulla, Handelsman, David J, Maitz, Peter K, Wang, Yiwei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-08-2020; MDPI
• Subjects: Androgens; Androgens - administration & dosage; Androgens - pharmacology; Animals; Body composition; Body weight; Body Weight - drug effects; Burns; Burns - blood; Burns - drug therapy; Burns - immunology; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Chemokines; Collagen; Collagen - metabolism; Cytokines; Cytokines - blood; Dihydrotestosterone; Dihydrotestosterone - administration & dosage; Dihydrotestosterone - pharmacology; Disease Models, Animal; Energy; Enumeration; Flow cytometry; Growth factors; Hormones; Inflammation; Inflammatory response; Macrophages; major burn injury; Male; Mice; Monocytes; mouse model; Rodents; Spleen; Spleen - drug effects; Spleen - immunology; Testosterone; Weight reduction; Wound healing; Wound Healing - drug effects; wound healing; androgens; mouse model; inflammation; dihydrotestosterone; major burn injury
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21176231

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.