TESTOSTERONE AND OR LOW ESTRADIOL - NORMALLY REQUIRED BUT HARMFUL IMMUNOLOGICALLY FOR MALES AFTER TRAUMA-HEMORRHAGE/

Citation
Mk. Angele et al., TESTOSTERONE AND OR LOW ESTRADIOL - NORMALLY REQUIRED BUT HARMFUL IMMUNOLOGICALLY FOR MALES AFTER TRAUMA-HEMORRHAGE/, The journal of trauma, injury, infection, and critical care, 44(1), 1998, pp. 78-84
Citations number
33
Categorie Soggetti
Emergency Medicine & Critical Care
Volume
44
Issue
1
Year of publication
1998
Pages
78 - 84
Database
ISI
SICI code
Abstract
Background: Previous studies indicate that after severe hemorrhage, im mune functions are markedly depressed in males, whereas females do not show any depression, Although androgen depletion by castration of mic e before soft-tissue trauma and hemorrhagic shock patients the depress ion of cell-mediated immunity, it remains unknown whether testosterone per se is responsible for producing immune depression, Methods: Femal e C3H/HeN mice were pretreated with 5 alpha-dihydrotestosterone (DHT) or vehicle for 20 days, The mice then underwent soft-tissue trauma (la parotomy) and hemorrhagic shock (blood pressure 35 +/- 5 mm Hg for 90 minutes) followed by adequate fluid resuscitation (shed blood and lact ated Ringer's solution) or sham operation, Two groups of nontreated ma le C3H/HeN mice were included as controls: one group was subjected to hemorrhagic shock followed by resuscitation, and the second group unde rwent only sham operation, At 24 hours after trauma-hemorrhage and res uscitation, animals were killed, macrophages harvested from the perito neum and spleen, and their ability to release interleukin (IL)-1 and I L-6 was evaluated, Plasma DHT, estradiol, and corticosterone levels we re measured by radioimmunoassay. Results: Treatment of female mice wit h DHT produces a significant increase in DHT levels that was comparabl e with those seen in nontreated male mice, Alternatively, estradiol le vels in female mice were significantly depressed by DHT treatment to l evels comparable with those observed in control males, In the vehicle- treated female mice, no depression of the macrophage function was evid ent after trauma hemorrhage, In contrast, testosterone-treated female mice that had experienced hemorrhage shelved significant depression in splenic and peritoneal macrophage IL-1 and IL-6 production, comparabl e with the values seen in macrophages from male mice that had experien ced hemorrhage, Conclusions: These findings indicate that pretreatment of Female mice with DHT depresses macrophage function after trauma-he morrhage, which mimics the changes seen in normal male mice subjected to trauma-hemorrhage. We propose, therefore, that high testosterone an d/or low estradiol levels are responsible for producing the immune dep ression in male mice after trauma-hemorrhage, Testosterone receptor bl ocking agents, e.g., flutamide, and/or estradiol administration should thus be useful adjuncts for preventing immune depression in male trau ma patients.