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
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.