Androstenediol modulates sepsis induced alterations of survival and immune functions in a murine model of sepsis.

Abstract

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 48 h 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.

• Authors: Daniel Schmitz, Sven Lendemans, Reiner Oberbeck
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 10 Issue 2 Pg. 137-43 (Mar 2014) ISSN: 1875-6638 [Electronic] Netherlands
• PMID: 23432316 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Dehydroepiandrosterone
• Androstenediol

Topics

• Administration, Intravenous
• Androstenediol (administration & dosage, pharmacology)
• Animals
• Apoptosis (drug effects)
• Body Temperature
• Cytokines (biosynthesis, metabolism)
• Dehydroepiandrosterone (administration & dosage, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Injections, Subcutaneous
• Male
• Mice
• Mice, Inbred Strains
• Molecular Conformation
• Sepsis (drug therapy, immunology, metabolism)
• Spleen (cytology, drug effects, immunology)
• Survival Rate