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

被引:40
作者
Knöferl, MW
Angele, MK
Catania, RA
Diodato, MD
Bland, KI
Chaudry, IH
机构
[1] Univ Alabama, Dept Surg, Sch Med, Birmingham, AL 35294 USA
[2] Univ Alabama, Sch Med, Surg Res Ctr, Birmingham, AL 35294 USA
关键词
inflammation; cytokines; gender;
D O I
10.1152/japplphysiol.01201.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 mug/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-gamma, IL-10 release, and splenic Mphi IL-1beta, 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-gamma, release, and splenic Mphi IL-1beta, 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 Mphi 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.
引用
收藏
页码:529 / 535
页数:7
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