Physiological levels of 5 alpha-dihydrotestosterone depress wound immune function and impair wound healing following trauma-hemorrhage.
OBJECTIVE
Studies indicate that a depressed wound immune function contributes to an increased rate of wound complications and impaired wound healing following trauma-hemorrhage (T-H). Androgen, ie, 5 alpha-dihydrotestosterone, is responsible for producing the depressed systemic cell-mediated immune responses following T-H in males. The aim of the present study was to determine whether depletion of 5 alpha-dihydrotestosterone in males before T-H has any salutary effects on wound immune cell function and wound healing in male mice following T-H.


METHODS
Mice were castrated or sham castrated 14 days before midline laparotomy (ie, tissue trauma) and subcutaneous polyvinyl sponge implantation, followed by hemorrhage (mean +/- SEM blood pressure, 35 +/- 5 mm Hg for 90 minutes and resuscitation) or sham operation. At 24 hours thereafter, wound immune cells from the sponges were harvested and cultured with lipopolysaccharide A. Release of interleukin 1 beta (IL-1 beta) and IL-6 (in picograms per milliliter) was determined in the supernatants by enzyme-linked immunosorbent assay. In addition, IL-6 was assessed at the wound site by immunohistochemistry. Ten days after T-H, wound-breaking strength was measured.


RESULTS
Precastration prevented the significantly suppressed capacity of wound immune cells to release IL-1 beta and IL-6. In addition, precastration normalized the elevated IL-6 expression at the wound site in the T-H mice. Moreover, wound-breaking strength was improved in castrated mice 10 days after T-H.


CONCLUSIONS
Male sex steroids appear to be responsible for wound immune cell dysfunction following trauma and severe blood loss. Because decreasing androgen levels resulted in improved wound healing, our results suggest that the use of androgen receptor-blocking agents, eg, flutamide, following T-H might represent a novel adjunct for decreasing the rate of wound complications under those conditions.
Nitsch
Stefan M
SM
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Wittmann
Florian
F
Angele
Peter
P
Wichmann
Matthias W
MW
Hatz
Rudolf
R
Hernandez-Richter
Thomas
T
Chaudry
Irshad H
IH
Jauch
Karl W
KW
Angele
Martin K
MK
D000704:Analysis of Variance; D000818:Animals; D002369:Castration; D016207:Cytokines / Q000032:analysis*; D013196:Dihydrotestosterone / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D007111:Immunity, Cellular / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000276:immunology* / Q000628:therapy; D014945:Wound Healing / Q000276:immunology* / Q000502:physiology; D014947:Wounds and Injuries / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D016207:Cytokines; D013196:Dihydrotestosterone