Testosterone receptor blockade restores cellular immunity in male mice after burn injury

Abstract

Males are known to have increased risk for septic complications after traumatic injury, which appears to be mediated by the inhibitory effects of testosterone on immune function. The role of testosterone in immunity after burn injury, however, remains unclear. Herein, we examined the effects of a testosterone receptor antagonist, flutamide, on delayed type hypersensitivity response (DTH), splenocyte proliferation, interleukin (IL)-2 secretion, and IL-2 receptor (IL-2R) expression in male BALB/c mice subjected to a 15% total body surface area burn or sham injury. Burn-or sham-injured mice were given flutamide s.c. at 30 min and 24 h after injury. At 48 h, burn injury caused a 48% (P<0·001) decrease in DTH response; however, mice that received flutamide treatment did not demonstrate significant suppression of DTH. Likewise, splenocyte proliferation and IL-2 production were depressed in burned animals in comparison with sham-injured controls, and flutamide treatment resulted in a partial restoration of these responses. In vitro studies indicated that splenocytes from sham-and burninjured mice were equally sensitive to the suppressive effects of 5 -dihydrotestosterone in regard to proliferation and IL-2 production. Further evaluation revealed a decrease in IL-2R expression on splenocytes from burned mice and a partial restoration of this expression with flutamide treatment. Thus blocking testosterone receptor activation improves the cellular immunity in thermally injured mice, possibly through restoration of IL-2 production and IL-2R expression. It remains to be determined whether the effects of testosterone in this injury model are direct or indirect.

Augmentation of T Cell Levels and Responses Induced by Androgen Deprivation

“…It has long been appreciated that gonadal sex steroids might modulate systemic host immunity (1,9,10,12,24). For instance, autoimmunity has been shown to be more prevalent in women than in men (2-4).…”

“…Splenocytes derived from Cx compared with Sx mice have also been shown to produce higher levels of IL-2 and IFN-␥ in response to Con A, and increased autoreactive Ab in response to mitogen (12). Additionally, studies have shown that AD may reduce host immunosuppression induced by hemorrhage (1) or burn injury (24). Thus, prompted by these observations, we set out to investigate the impact of AD on Ag/tissue-specific T cell responses in postpubertal Cx compared with Sx mice.…”

Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency

“…Monocyte-derived macrophages also express androgen receptors (McCrohon et al 2000) and these cells may metabolize testosterone to 5 -dihydrotestosterone (Araneo et al 1991). In this regard, treatment of mice with flutamide, an androgen-receptor blocker, restores previously depressed cellular immunity after brain injury (Messingham et al 2001). However, to the best of our knowledge no study has been reported so far in which the expression of androgen receptors is analyzed in DCs.…”

Facial masculinity is related to perceived age but not perceived health

“…Folstad & Karter's (1992) Immunocompetence Hypothesis proposes that secondary sexual features (those resulting from sex hormones) are honest signals of genetic quality because sex hormones, specifically testosterone, are deleterious to the immune system (Angele & Faist, 2000;Messingham, Shirazi, Duffner, Emanuele & Kovacs, 2001). Only high quality, healthy males may be able to tolerate the immunosuppressive effects of testosterone and develop exaggerated secondary sexual traits.…”