DHEA and sepsis

Intensive Care Med. 2007 Sep 26; [Epub ahead of print]

Dehydroepiandrosterone: a modulator of cellular immunity and heat shock
protein 70 production during polymicrobial sepsis.

Oberbeck R, Deckert H, Bangen J, Kobbe P, Schmitz D.

Department of Trauma Surgery, University Hospital of Essen,
Hufelandstrasse 55, 45147, Essen, Germany,

OBJECTIVE: DHEA is an immunomodulatory steroid hormone that improves
survival during systemic inflammation. A DHEA-induced modulation of heat
shock protein response may be an alternative mechanism contributing to the
beneficial effects of this hormone. We investigated the effect of DHEA
administration on survival, cellular immune functions, and HSP-70
production in septic mice. DESIGN AND SETTING: Randomized animal study,
level I trauma center, university research laboratory. SUBJECTS: Male NMRI
mice. INTERVENTIONS: Mice were subjected to sham operation (laparotomy,
LAP) or sepsis (cecal ligation and puncture, CLP) with or without
administration of either saline 0.9% (LAP, CLP) or 20[Symbol: see
text]mg/kg DHEA subcutaneously (LAP/DHEA, CLP/DHEA). Survival was monitored
over a 48-h period. Splenocyte apoptosis rate (AnnexinV binding),
splenocyte proliferation ([(3)H]thymidine incorporation), TNF-alpha plasma
concentration (ELISA), and HSP-70 concentration (ELISA) in tissue extracts
from liver, lung, and spleen were monitored 48[Symbol: see text]h after
onset of sepsis. RESULTS: DHEA administration improved the survival of
septic mice (78% vs. 50%). This effect was paralleled by increased
splenocyte proliferation, decreased cellular apoptosis rate of splenocytes,
and attenuation of TNF-alpha release. Furthermore, an increased HSP-70
concentration was observed in lungs and spleens of DHEA-treated septic
animals. CONCLUSIONS: DHEA-treatment decreased the mortality rate of septic
mice. This was accompanied by improved cellular immune functions and an
augmented heat shock response (HSP-70) of lungs and spleens. Further
studies are required to demonstrate a direct relationship between the
improved survival and the observed alterations in the immune system in
DHEA-treated animals.
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