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


METHODS
Randomized animal study, level I trauma center, university research laboratory.


METHODS
Male NMRI mice.


METHODS
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 mg/kg DHEA subcutaneously (LAP/DHEA, CLP/DHEA). Survival was monitored over a 48-h period. Splenocyte apoptosis rate (AnnexinV binding), splenocyte proliferation ([3H]thymidine incorporation), TNF-alpha plasma concentration (ELISA), and HSP-70 concentration (ELISA) in tissue extracts from liver, lung, and spleen were monitored 48 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.
Oberbeck
Reiner
R
Department of Trauma Surgery, University Hospital of Essen, Hufelandstrasse 55, 45147 Essen, Germany. reineroberbeck@hotmail.com
Deckert
Hanno
H
Bangen
Jörg
J
Kobbe
Phillip
P
Schmitz
Daniel
D
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011897:Random Allocation; D018805:Sepsis / Q000378:metabolism* / Q000382:microbiology; D016019:Survival Analysis
D000276:Adjuvants, Immunologic; D018840:HSP70 Heat-Shock Proteins; D003687:Dehydroepiandrosterone