Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage?
OBJECTIVE
Administration of female sex steroids in males after trauma-hemorrhage has salutary effects on the depressed immune responses.


METHODS
Randomized laboratory experiment.


METHODS
Male C3H/HeN mice were subjected to midline laparotomy and hemorrhagic shock (35+/-5 mm Hg for 90 minutes, then resuscitation) or sham operation and received subcutaneous 17beta-estradiol (40 microg/kg body weight) or corn oil vehicle at the beginning of resuscitation.


METHODS
At 24 hours after hemorrhage, the animals were killed and plasma 17beta-estradiol and IL-6, splenocyte interleukin (IL) 2, IL-3, and IL-10 production as well as splenic and peritoneal macrophage IL-1beta, IL-10, and IL-6 release were measured.


RESULTS
Splenocyte IL-2 and IL-3 release were significantly depressed after hemorrhage in vehicle-treated mice (P<.05, analysis of variance). Treatment with 17beta-estradiol after hemorrhage led to the restoration of splenocyte IL-2 and IL-3 release. The depressed proinflammatory cytokine (IL-1 and IL-6) release seen in splenic and peritoneal macrophages was restored in the 17beta-estradiol-treated hemorrhage group. In contrast, the sustained release of the anti-inflammatory cytokine IL-10 by splenocytes and splenic and peritoneal macrophages in vehicle-treated mice after hemorrhage was decreased in 17beta-estradiol-treated mice. The increase in circulating IL-6 levels after hemorrhage was significantly attenuated in 17beta-estradiol-treated mice. Although administration of 17beta-estradiol increased plasma 17beta-estradiol levels by approximately 100% in sham as well as hemorrhage groups, improved immune responses were seen only in posthemorrhage 17beta-estradiol-treated mice. There was no adverse effect of 17beta-estradiol treatment in the sham or posthemorrhage groups.


CONCLUSIONS
Since administration of a single dose of 17beta-estradiol in males after trauma-hemorrhage restores the immune functions and decreases circulating levels of IL-6, hormones with estrogenic properties should be considered as safe and novel therapeutic agents for restoring the immune responsiveness in male trauma victims.
Knöferl
M W
MW
Center for Surgical Research and the Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, USA.
Diodato
M D
MD
Angele
M K
MK
Ayala
A
A
Cioffi
W G
WG
Bland
K I
KI
Chaudry
I H
IH
D000276:Adjuvants, Immunologic; D000818:Animals; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D007111:Immunity, Cellular; D007378:Interleukins / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011897:Random Allocation; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D007378:Interleukins; D004958:Estradiol