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

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-α 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-α 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.