Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage.
Studies indicate that macrophage immune responses in males are depressed after trauma-hemorrhage, whereas they are enhanced in females under such conditions. Nonetheless, the involvement of male and female sex steroids in this gender-dependent dimorphic immune response after trauma-hemorrhage remains unclear. To study this, male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or a combination of both steroid hormones for 14 days before soft tissue trauma (i.e., laparotomy) and hemorrhagic shock (35 +/- 5 mmHg for 90 min followed by adequate fluid resuscitation) or a sham operation. Twenty-four hours later the animals were killed, plasma was obtained, and Kupffer cell and splenic and peritoneal macrophage cultures were established. For DHT-treated mice, we observed significantly decreased releases of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-6 by splenic macrophage (-50 and -57%, respectively) and peritoneal macrophage (-51 and -52%, respectively) cultures after trauma-hemorrhage compared with releases by cultures of cells from mice subjected to a sham operation; in contrast, responses of splenic and peritoneal macrophage cultures from other groups subjected to trauma-hemorrhage did not change significantly. In addition, only DHT-treated animals exhibited increased Kupffer cell IL-6 release (+634%). The release of IL-10 in DHT-treated hemorrhaged animals was increased compared with that in sham-operated animals but was decreased in estrogen-treated mice under such conditions. These results suggest that male and female sex steroids exhibit divergent immunomodulatory properties with respect to cell-mediated immune responses after trauma-hemorrhage.
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903, USA.
M K
MK
Angele
M W
MW
Knöferl
M G
MG
Schwacha
A
A
Ayala
W G
WG
Cioffi
K I
KI
Bland
I H
IH
Chaudry
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology; D004338:Drug Combinations; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006470:Hemorrhage / Q000097:blood / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D014947:Wounds and Injuries / Q000097:blood / Q000378:metabolism*
D016207:Cytokines; D004338:Drug Combinations; D012739:Gonadal Steroid Hormones; D018836:Inflammation Mediators; D013196:Dihydrotestosterone; D004958:Estradiol