Gender-Specific Immune Response Following Shock: Clinical and Experimental Data

Abstract

Several clinical and experimental studies demonstrate an increased susceptibility to and morbidity from shock, trauma, and sepsis in males compared to females. Moreover, cell-mediated immune responses have been found to be unchanged or enhanced in females whereas they are depressed in males following trauma hemorrhage. Sex hormones mediate this gender dimorphism of the immune response following shock. In this respect, male sex hormones have been shown to exhibit immunosuppressive properties following trauma-hemorrhage. In contrast, female sex steroids appear to be immunoprotective under those conditions. The precise underlying mechanisms for these immunomodulatory properties of sex steroids following shock, however, remain unknown. Both direct and indirect effects might act synergistically in mediating the immunomodulatory effects of sex hormones. Depletion of androgens prevented the depression of cardiovascular responses following trauma-hemorrhage which might contribute to maintained immune responses in testosterone-depleted animals. Furthermore, sex hormone receptors have been identified on various immune cells suggesting direct effects. In experimental animal models, administration of the testosterone receptor blocker flutamide or treatment with female sex steroids has been demonstrated to prevent immunodepression following trauma-hemorrhage and to decrease the mortality from subsequent sepsis. Thus, the immunomodulatory properties of sex hormones following trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.