Abstract
IntroductionDehydroepiandrosterone (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.MethodsMale 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-α, IL-1β and IL-10 mRNA expression pattern were investigated in lung and liver tissue after 48 and 96 hours.ResultsDHEA treatment resulted in a significantly reduced mortality rate and improvements in the clinical status. On cytokine level, only TNF-α 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-α was up-regulated in the CLP-vehicle group while remaining moderate by DHEA treatment in liver tissue.ConclusionsThe improved outcome after DHEA treatment and trauma is coherent with restoration of TNF-α in liver and lung after 48 hours and a counter-regulatory attenuation of TNF-α in liver after 96 hours. Thus, DHEA seems to act, time and organ dependent, as a potent modulator of TNF-α expression.
Highlights
Dehydroepiandrosterone (DHEA) improves survival after trauma and sepsis, while mechanisms of action are not yet fully understood
After 96 hours, TNF-α was upregulated in the cecal ligation and puncture (CLP)-vehicle group while remaining moderate by DHEA treatment in liver tissue
The improved outcome after DHEA treatment and trauma is coherent with restoration of TNF-α in liver and lung after 48 hours and a counter-regulatory attenuation of TNF-α in liver after 96 hours
Summary
Dehydroepiandrosterone (DHEA) improves survival after trauma and sepsis, while mechanisms of action are not yet fully understood. Sepsis and associated diseases such as systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome are common posttraumatic complications in intensive care units. These patients are at high risk of developing multiple organ dysfunction syndrome with subsequent multiple organ failure. TNF-α plasma levels correlate with the severity of sepsis and with patients' outcome [3]. It induces the expression of secondary cytokines, such as IL-6 and IL-10. Previous studies of our group showed that induction of sepsis by cecal ligation and puncture (CLP) leads to a significant increase in the plasma levels of TNF-α, IL-6, and IL-10 [4]
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