title: DHEA-dependent and organ-specific regulation of TNF-alpha mRNA expression in a murine polymicrobial sepsis and trauma model.
abstract: BACKGROUND
  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-1beta 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.
authors: Department of Trauma Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. barkhausen.tanja@mh-hannover.de
authors: Tanja
authors: T
authors: Barkhausen
authors: Frank
authors: F
authors: Hildebrand
authors: Christian
authors: C
authors: Krettek
authors: Martijn
authors: M
authors: van Griensven
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000235:genetics* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D018805:Sepsis / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000235:genetics* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003687:Dehydroepiandrosterone