title: Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors.
abstract: OBJECTIVE
  Peripheral blood mononuclear cell (PBMC) dysfunction occurs following major abdominal surgery and correlates with an increased rate of septic complications. Studies have shown that dehydroepiandrosterone (DHEA) restores cell-mediated immune responses after trauma-hemorrhage in mice. Nonetheless, it remains unknown whether DHEA has any salutary effects on depressed PBMC function in surgical patients.
  
  
  METHODS
  Laboratory experiment.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Fifteen patients undergoing major abdominal surgery.
  
  
  METHODS
  Blood samples were obtained preoperatively and 2 hrs postoperatively.
  
  
  RESULTS
  PBMCs were cultured with 33% plasma in the presence or absence of DHEA (10(-10) M, 10(-8) M physiologic concentration, 10(-6) M, 10(-5) M). In an additional set of samples, the estrogen receptor antagonist tamoxifen (10(-6) M) was added. The release of proinflammatory cytokines (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) was measured in the supernatants by enzyme-linked immunosorbent assay. Abdominal surgery resulted in depressed interleukin-1beta and tumor necrosis factor-alpha release by PBMC. Addition of DHEA to the culture medium, however, significantly improved the release of interleukin-1beta and tumor necrosis factor-alpha and stimulated the interleukin-6 release capacity of PBMC. This effect was most pronounced for a concentration of 10(-5)M DHEA. The immunomodulatory effect of DHEA on PBMC cytokine release was completely blocked by tamoxifen. In contrast, the modulatory effect of DHEA was enhanced by the addition of postoperative plasma.
  
  
  CONCLUSIONS
  DHEA stimulates proinflammatory cytokine release capacities of human PBMCs following major abdominal surgery. The estrogen receptor appears to be involved in mediating the immunomodulatory effect of DHEA. Thus, DHEA might be a useful adjunct for preventing immunosuppression in surgical patients.
authors.affiliation: Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Markus C
authors.initials: MC
authors.lastname: Frantz
authors.forename: Niclas J
authors.initials: NJ
authors.lastname: Prix
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Wichmann
authors.forename: Natasja K
authors.initials: NK
authors.lastname: van den Engel
authors.forename: Thomas
authors.initials: T
authors.lastname: Hernandez-Richter
authors.forename: Eugen
authors.initials: E
authors.lastname: Faist
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.forename: Martin K
authors.initials: MK
authors.lastname: Angele
mesh_terms: D000005:Abdomen / Q000601:surgery; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; D003687:Dehydroepiandrosterone