Androstenediol Modulates Sepsis Induced Alterations of Survival and Immune Functions in a Murin Model of Sepsis
Background: Recently the benefit of subcutaneously applied dehydroepiandrosterone (DHEA) during sepsis
was demonstrated. It was therefore supposed that the impact of DHEA might be induced by its metabolite androstenediol
produced via conversion in subcutaneous tissue. Thus we postulate a comparable impact of intravenously applied androstenediol
like DHEA. Material and Methods: Male NMRI mice were subjected to sham-operation (laparotomy) or sepsis
(cecal ligation and puncture). Animals received saline, DHEA (20 mg/kg/day) subcutaneously, androstenediol (20
mg/kg/day) subcutaneously and androstenediol (10 mg/kg/day) intravenously. During 48h of sepsis and treatment clinical
parameters such as survival and body temperature were observed. Termination of animals was performed 48 hrs after induction
of sepsis in order to monitor splenocyte apoptosis (Annexin V binding capacity), cytokine release (IL-10 and
TNF-α, ELISA), and immunological capacity by DTH-Reaction (Delayed type of hypersensitivity). Results: Subcutaneous
and intravenous androstenediol administration improved the survival rate of septic mice 48 hrs after induction of CLP
like subcutaneous administration of DHEA. (86% vs 53%). This effect was paralleled by a restoration of splenocyte proliferation
and DTH reaction, a decreased cellular apoptosis rate of splenocytes, and an attenuation of cytokine release.
Conclusions: Administration of androstenediol induces an increased survival rate and improved cellular immune functions
in septic mice. This effect was detected independent of the way of administration and is comparable to those effects induced
by subcutaneous DHEA administration. With respect to clinical use during critical illness, intravenous administration
of androstenediol seems to be an alternative to subcutaneous DHEA administration.
Keywords: Androstenediol, mouse, sepsis, survival, way of application.
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