Immunoprotection in proestrus females following trauma-hemorrhage: the pivotal role of estrogen receptors.
Immune responses in proestrus females are not altered after trauma-hemorrhage, whereas they are markedly depressed in males. Elevated levels of female sex steroids appear to be responsible for maintaining immune responses but it remains unknown, whether estrogen per se is responsible. To study this, proestrus female C3H/HeN mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35+/-5 mmHg for 90 min, then resuscitated) or sham operation and received the estrogen receptor antagonist EM-800 or vehicle during resuscitation. Two hours following trauma-hemorrhage, splenocyte proliferation, IL-2, IL-3, IFN-gamma release, and splenic macrophage IL-6 release was maintained in vehicle-treated females. In EM-800-treated females, however, these immune parameters were significantly depressed. Following trauma-hemorrhage, Kupffer cell TNF-alpha release and circulating TNF-alpha were increased only in EM-800-treated females. These findings indicate that the ability of proestrus females to maintain immune function following trauma-hemorrhage is estrogen-dependent and mediated via estrogen receptors.
Knöferl
Markus W
MW
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, Volker Hall, G094 1670 University Blvd., Birmingham, AL 35294-0019, USA.
Angele
Martin K
MK
Schwacha
Martin G
MG
Anantha Samy
T S
TS
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D005260:Female; D006470:Hemorrhage / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000097:blood; D007728:Kupffer Cells / Q000502:physiology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D011359:Proestrus / Q000276:immunology*; D011422:Propionates / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000276:immunology*
D001578:Benzopyrans; D007376:Interleukin-2; D015850:Interleukin-6; D011422:Propionates; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; C106945:EM 800