The Role of Androgens in Burn Wound Healing

Abstract

Background/Objective: Androgens are not currently part of the therapeutic guidelines in burns management. However, oxandrolone, an androgen analogue, has been reported to have significant benefits in burn wound recovery, but there are still concerns regarding its side effect profile. Preliminary studies have identified that the inactivation of androgen receptors (AR) slows wound healing post-burn injury. This finding is opposite to that of experimental evidence for androgens in cutaneous (non-burn) wound healing, on which they exert an inhibitory effect. Therefore, this study aimed to identify the role of androgen signalling in severe, hypermetabolic burn injury both at the local wound and systemic levels. Design: Experimental study. Setting: Research laboratory. Subjects: Male Balb/c mice; wild type (WT) and androgen receptor knockout (ARKO) using Cre/LoxP system. Interventions: 4 cm2 contact burn injury (representing 10% Total Body Surface Area (TBSA)). Main Results: ARKO mice demonstrated slower wound healing and poorer body weight maintenance and recovery. This was associated with preferential activation of white adipose tissue over brown adipose tissue, larger splenic size and smaller hepatic size. There was no difference in local wound inflammatory cytokine mRNA expression between WT and ARKO mice. Conclusions: Androgens play a positive modifying role in wound healing in the context of burn injury, a finding opposite to its reported inhibitory actions in cutaneous wound healing. This is likely resultant from an attenuation of the systemic hypermetabolic response. This contradictory, contextdependent action urges further research into the beneficiary effects of androgens in burns management, particularly its modulation of systemic inflammation and the host immune response.