Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors.
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.
Frantz
Markus C
MC
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Prix
Niclas J
NJ
Wichmann
Matthias W
MW
van den Engel
Natasja K
NK
Hernandez-Richter
Thomas
T
Faist
Eugen
E
Chaudry
Irshad H
IH
Jauch
Karl-Walter
KW
Angele
Martin K
MK
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
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; D003687:Dehydroepiandrosterone