The effect of dehydroepiandrosterone on hemorrhage-induced suppression of cellular immune function

Intensive Care Med. 2002 Jul;28(7):963-8. doi: 10.1007/s00134-002-1292-8. Epub 2002 Apr 30.

Abstract

Objective: To determine whether the steroid hormone dehydroepiandrosterone (DHEA) improves cellular immune functions after hemorrhagic shock.

Design and setting: Prospective controlled study in a research laboratory at an university medical center.

Subjects: Male NMRI mice.

Interventions: Animals received 0.9% saline or DHEA (20 mg/kg subcutaneously) before induction of a volume-controlled hemorrhagic shock (55% of estimated circulating blood volume) by retro-orbital puncture. One hour after hemorrhage mice underwent fluid resuscitation by intravenous infusion of lactated Ringer's solution (300% of the shed blood). Separate groups of mice were killed to obtain whole blood and spleen 1 h after hemorrhage, 1 h after fluid resuscitation, and 24 h after hemorrhage to determine lymphocyte distribution (CD4(+), CD8(+), NK1.1-AG(+)), splenocyte apoptosis, and plasma concentrations of tumor necrosis factor-alpha and interleukin-10.

Measurements and results: Hemorrhage in control mice was associated with a rapid increase in circulating NK cell numbers. Elevated splenocyte apoptosis, an increased CD4/CD8 ratio, and decreased number of circulating CD8(+) T-cells was observed 24 h after hemorrhagic shock. DHEA administration was accompanied by a normalization of splenocyte apoptosis and lymphocyte migration. Induction of hemorrhagic shock did not affect TNF-alpha or IL-10 plasma concentrations in either treatment group.

Conclusions: DHEA administration improves cellular immune function after hemorrhage and may therefore be beneficial in patients with hemorrhagic shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CD4-CD8 Ratio
  • Dehydroepiandrosterone / pharmacology*
  • Dehydroepiandrosterone / therapeutic use
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunity, Cellular / drug effects*
  • Interleukin-10 / blood
  • Killer Cells, Natural / immunology
  • Male
  • Mice
  • Prospective Studies
  • Shock, Hemorrhagic / blood
  • Shock, Hemorrhagic / drug therapy*
  • Spleen / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Dehydroepiandrosterone