Dehydroepiandrosterone, an endogenous immune modulator, after traumatic shock

Michael J. Schurr, Timothy C. Fabian, Martin A. Croce, Lisa E. Varnavas, Kenneth G. Proctor

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Dehydroepiandrosterone (DHEA), an endogenous immune modulator, reduces mortality after endotoxin (lipopolysaccharide (LPS)) administration in rodents. However, there have been no studies in clinically relevant large-animal models. A unique experimental model is used to study the effects of DHEA in resuscitated trauma and to evaluate the protective effect of DHEA on the systemic inflammatory response induced by a delayed LPS challenge. Anesthetized, ventilated pigs were instrumented and then subjected to local hind-limb trauma and 35% hemorrhage. After 1 h, animals were resuscitated with shed blood, supplemental Ringers solution, and in a randomized, blinded fashion, 4 mg/kg of DHEA or vehicle. Two additional groups received 10 mg/kg or 20 mg/kg of DHEA. Animals were dosed again at 24, 48, and 72 h. After 75 h, Escherichia coli LPS was administered. LPS caused a fall in DHEA levels (0.23 ±.05 ng/mL (60 min post-LPS) versus .94 ± 35 ng/mL (72 h), p = .01). DHEA levels 60 min post-LPS were significantly higher in treated animals (p < .002). After LPS, all groups manifested progressive septic symptoms with a hyperdynamic state and pulmonary failure. These symptoms were not blunted by the administration of DHEA. DHEA levels are suppressed by LPS in this two-stage model of trauma and delayed sepsis; however, exogenous DHEA administration fails to blunt the associated systemic inflammatory response and pulmonary failure.

Original languageEnglish (US)
Pages (from-to)55-59
Number of pages5
JournalShock
Volume7
Issue number1
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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