Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage

Abstract

. Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage. J Appl Physiol 101: 448 -453, 2006. First published April 13, 2006; doi:10.1152 doi:10. /japplphysiol.00166.2006eral studies indicate that cell-mediated immune responses, i.e., macrophage (M⌽) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after traumahemorrhage in male mice. Testosterone has been shown to be responsible for the depression of M⌽ cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 Ϯ 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic M⌽ was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic M⌽ after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in M⌽ from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic M⌽ after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss. antigen presentation; immunosuppression

Suppression of Activation and Costimulatory Signaling in Splenic CD4+ T Cells after Trauma-Hemorrhage Reduces T-Cell Function

“…This matches the clinical experience in that patients are at high risk of immune suppression and subsequent infection even though their major injury has been successfully treated. 57 In addition to the well known fact that posttraumatic suppression of adaptive immunity is due to reduced major histocompatability complex II expression and impaired antigen presentation, 8,58,59 our current study indicated that dysregulation of T-cell costimulatory signaling may also play a crucial role in the induction of T-cell anergy after trauma-hemorrhage.…”

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

“…Similarly, a significant decrease in the release of the proinflammatory cytokines IL-1β and IL-6 by splenic macrophages and peritoneal macrophages was observed in DHT-treated castrated male mice following trauma-hemorrhage (91). MHC class II expression was also shown to be decreased in peritoneal and splenic macrophages after trauma-hemorrhage (92). Estrogens have been shown to increase the resistance of host animals to infections and also stimulate macrophage functions, suggesting that female sex steroids should improve macrophage function in contrast to the immunodepressive effects of male sex steroids (93)(94)(95).…”

Effect of Sex Steroids on Babesia microti Infection in Mice

“…41 Mayr and others reported that major histocompatibility class II expression by macrophages in male mice was suppressed after traumainduced hemorrhage, and that this suppression was prevented by castration. 42 In male mice, these alterations in immune function, which may be caused by the lack of testosterone after orchidectomy, might control parasitemia increases and aggravation of anemia in infected orchidectomized mice.…”