Plasma dehydroepiandrosterone levels during experimental endotoxemia and anti-inflammatory therapy in humans

Objective: To measure the effect of experimental endotoxemia and anti-inflammatory therapy on plasma dehydroepiandrosterone (DHEA) levels in humans. Design:Controlled, randomized, single-blind, prospective clinical study. Setting: Monitored unit in research hospital. Subjects: Twelve healthy volunteers served as their own controls and were randomized to receive intravenous endotoxin (Escherichia coli) or saline separated by 1 wk. Six were randomized to receive ibuprofen, a cyclooxygenase inhibitor, and six were given placebo. Interventions: Measurement of vital signs and hormones during a 24-hr period, Measurements and Main Results:AII subjects given endotoxin had a significant increase in plasma DHEA, cortisol, and adrenocorticotropic hormone (ACTH) levels (all p = .02). DHEA levels were maximum at 2 hrs and returned to baseline Values by 6 hrs. Ibuprofen administration significantly blunted the endotoxin-induced increase in DHEA secretion (p = .001), whereas the increase in cortisol and ACTH was not affected. Conclusions: Acute endotoxemia leads to a rise in plasma DHEA levels in humans. Maximum levels of DHEA but not cortisol or ACTH were blunted by ibuprofen, suggesting a different regulation of these synthetic pathways in the adrenal cortex inner zone during acute inflammation.