Showing papers by "Eugen Faist published in 2005"

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. Design Laboratory experiment. Setting University laboratory. Patients Fifteen patients undergoing major abdominal surgery. Interventions Blood samples were obtained preoperatively and 2 hrs postoperatively. Measurements and main 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.

Einfluss von chirurgischem Trauma auf die Expression von Steroidhormonrezeptoren in PBMCs bei Patienten

Abstract: Background: Animal experiments demonstrate a gender-specific immune response following trauma and hemorrhagic shock. In this respect, male (immunosuppressive) and female (immunoprotective) sex hormones have been found to be responsible for this gender dimorphism. An increased expression of androgen and a decreased expression of estrogen receptors in male animals seem to potentiate the immunomodulatory effect of sex hormones. The effect of surgical trauma on the expression of steroid hormone receptors in PBMCs (peripher blood mononuclear cells) in patients, however, remains unknown. Objective: To investigate whether surgical trauma affects the expression of sex hormones in patients. Methods: Blood samples were obtained from 14 patients (7 males, 7 females) undergoing major abdominal surgery preoperatively and 2 hours postoperatively. Plasma was collected and PBMCs were isolated by Ficoll separation. The expression of the androgen receptor as well as the estrogen α- and β- receptors were determined by rt-PCR. β-Actin was used as house keeping gene. Results: The results indicate that surgical trauma has no influence on the expression of the androgen receptor and the estrogen receptors α and β in male patients. Similarly, in females the expression of sex hormone receptors in PBMCs was unaltered following abdominal surgical interventions. Discussion: The data demonstrate that in contrast to mice no alterations in the expression of androgen and estrogen hormone receptors in immune cells were evident following surgery in patients. This difference might be responsible for the observation that male and female sex hormones did not show immunomodulatory effects on PBMCs of surgical patients. Those findings suggest that immunomodulatory approaches using sex hormones or their receptor antagonists following surgery and blood loss in mice cannnot directly be transferred to the clinic arena.

Einfluss von chirurgischem Trauma auf die Expression von Steroidhormonrezeptoren in PBMCs bei Patienten Influence of surgical trauma on the expression of steroid hormone receptors in PBMCs of patients

Abstract: Background: Animal experiments demonstrate a gender-specific immune response following trauma and hemorrhagic shock. In this respect, male (immunosuppressive) and female (immunoprotective) sex hormones have been found to be responsible for this gender dimorphism. An increased expression of androgen and a decreased expression of estrogen receptors in male animals seem to potentiate the immunomodulatory effect of sex hormones. The effect of surgical trauma on the expression of steroid hormone receptors in PBMCs (peripher blood mononuclear cells) in patients, however, remains unknown. Objective: To investigate whether surgical trauma affects the expression of sex hormones in patients. Methods: Blood samples were obtained from 14 patients (7 males, 7 females) undergoing major abdominal surgery preoperatively and 2 hours postoperatively. Plasma was collected and PBMCs were isolated by Ficoll separation. The expression of the androgen receptor as well as the estrogen α- and β- receptors were determined by rt-PCR. β-Actin was used as house keeping gene. Results: The results indicate that surgical trauma has no influence on the expression of the androgen receptor and the estrogen receptors α and β in male patients. Similarly, in females the expression of sex hormone receptors in PBMCs was unaltered following abdominal surgical interventions. Discussion: The data demonstrate that in contrast to mice no alterations in the expression of androgen and estrogen hormone receptors in immune cells were evident following surgery in patients. This difference might be responsible for the observation that male and female sex hormones did not show immunomodulatory effects on PBMCs of surgical patients. Those findings suggest that immunomodulatory approaches using sex hormones or their receptor antagonists following surgery and blood loss in mice cannnot directly be transferred to the clinic arena. Einleitung