Effect of gender and sex hormones on immune responses following shock.
Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of sex hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.
Angele
M K
MK
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
Schwacha
M G
MG
Ayala
A
A
Chaudry
I H
IH
D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D059002:Androgen Receptor Antagonists; D000818:Animals; D020296:Animals, Congenic; D000917:Antibody Formation / Q000187:drug effects / Q000502:physiology; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000627:therapeutic use; D004198:Disease Susceptibility; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009919:Orchiectomy; D011388:Prolactin / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D012727:Sex Characteristics; D012769:Shock / Q000188:drug therapy / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology; D014947:Wounds and Injuries / Q000276:immunology
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D016207:Cytokines; D018492:Dopamine Antagonists; D012739:Gonadal Steroid Hormones; D011453:Prostaglandins; D009569:Nitric Oxide; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D011388:Prolactin; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008787:Metoclopramide