Immunomodulatory effects of dehydroepiandrosterone in proestrus female mice after trauma-hemorrhage

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294 Submitted 30 December 2002 ; accepted in final form 7 April 2003 Studies indicate that administration of the adrenal steroid dehydroepiandrosterone (DHEA) after trauma-hemorrhage in male mice improved cellular immune functions and reduced mortality rates from subsequent sepsis. There is evidence, however, that DHEA is converted to estrogens in males and that estrogens are immunoprotective after trauma-hemorrhage (TH). In contrast, DHEA in females can be converted to testosterone that has deleterious effects on immune functions. The aim of our study, therefore, was to determine whether administration of DHEA in proestrus females after TH would deteriorate immune responses. Proestrus female C3H/HeN mice (age 7–8 wk) were subjected to laparotomy (i.e., soft tissue trauma induced) and hemorrhagic shock (35 ± 5 mmHg for 90 min) or sham operation. The mice then received DHEA (100 µ/25 g body wt) or vehicle subcutaneously followed by fluid resuscitation (4 x the shed blood volume). Plasma IL-6, splenocyte proliferation, splenocyte IL-2, IL-3, IFN- , IL-10 release, and splenic M IL-1 , IL-6, IL-10, and IL-12 release were determined 24 h after TH. Plasma IL-6 levels were significantly increased in vehicle-treated females, and DHEA administration markedly attenuated this response. In vehicle-treated females, splenocyte proliferation, IL-2, IL-3, and IFN- release, and splenic M IL-1 , IL-6, and IL-12 release were maintained or slightly enhanced after TH. In DHEA-treated females, however, these immune functional parameters were either unaltered compared with vehicle-treated animals or even further enhanced, but surprisingly were not depressed. Moreover, DHEA reduced splenocyte and splenic M anti-inflammatory cytokine (i.e., IL-10) production after TH compared with vehicle-treated females. Because DHEA further enhances the immune responsiveness in proestrus females after TH, this hormone might be a useful adjunct even in females for further enhancing immune responses and decreasing the mortality rate after trauma and severe blood loss. inflammation; cytokines; gender Address for reprint requests and other correspondence: I. H. Chaudry, Dept. of Surgery, Univ. of Alabama at Birmingham, Volker Hall, G094 1670 Univ. Blvd., Birmingham, AL 35294-0019 (E-mail: Irshad.Chaudry{at}ccc.uab.edu ).