Changes in dehydroepiandrosterone (DHEA) and DHEA-sulfate plasma levels during experimental endotoxinemia in healthy volunteers

Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) have immunomodulato ry effects in vitro and in vivo. Additionally, their plasma levels are alte red during chronic infection and inflammation. However, it remains unknown whether these steroids are involved in early host responses to infection in humans. We examined DHEA and DHEA-S levels during experimental endotoxinem ia, a well established pathophysiological model of bacterial infections in humans. Purified Salmonella abortus equi endotoxin (0.2, 0.4, or 0.8 ng/kg body weight) was injected in a single-blind, placebo-controlled experiment to 17 healthy male volunteers. During the following 12 h, rectal temperatur e and the plasma levels of ACTH, cortisol, DHEA, DHEA-S, interleukin 6, and tumor necrosis factor alpha were determined. Confirming earlier studies, t emperature and cytokine levels showed monophasic, dose-dependent increases in response to endotoxin. In contrast, endocrinological effects of endotoxi n showed a complex, biphasic pattern: cortisol levels were not affected by 0.2 ng/kg but significantly increased during the first 6 h following 0.4 an d 0.8 ng/kg endotoxin, whereas ACTH and DHEA levels were significantly enha nced during the first 6 h following 0.8 ng/kg only. ACTH, DHEA, and cortiso l secretion was blunted 6-12 h following 0.8 ng/kg. DHEA-S levels were unaf fected during the first 6 h following all dosages, but between 6-12 h after injection they were significantly increased following 0.2 ng/kg, unaffecte d by 0.4 ng/kg, and significantly decreased following 0.8 ng/kg endotoxin. The present results suggest that similarly to glucocorticoids, the adrenal androgens DHEA and DHEA-S play an important role during early host response s to bacterial infections in humans.