Introduction Dehydroepiandrosterone (DHEA) improves survival after trauma and sepsis, while mechanisms of action are not yet fully understood. Therefore, we investigated the influence of DHEA on local cytokine expression in a two-hit model. Methods Male NMRI mice were subjected to femur fracture/hemorrhagic shock and subsequent sepsis. Sham-operated animals were used as controls. DHEA (25 mg/kg) or vehicle was administered daily. Mortality rate, activity and body temperature were determined daily after sepsis induction. TNF-alpha, IL-1 beta and IL-10 mRNA expression pattern were investigated in lung and liver tissue after 48 and 96 hours. Results DHEA treatment resulted in a significantly reduced mortality rate and improvements in the clinical status. On cytokine level, only TNF-alpha was significantly reduced in the cecal ligation and puncture (CLP)-vehicle group in both tissues after 48 hours. This suppression could be restored by DHEA administration. In contrast, after 96 hours, TNF-alpha was up-regulated in the CLP-vehicle group while remaining moderate by DHEA treatment in liver tissue. Conclusions The improved outcome after DHEA treatment and trauma is coherent with restoration of TNF-alpha in liver and lung after 48 hours and a counter-regulatory attenuation of TNF-alpha in liver after 96 hours. Thus, DHEA seems to act, time and organ dependent, as a potent modulator of TNF-alpha expression.
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