Reversal of sexual dimorphism in splenic T lymphocyte responses after trauma-hemorrhage with aging

Previous studies have demonstrated that hemorrhagic shock produces immunode pression in young male mice, whereas the immunoresponsivness in young proes trus female mice is enhanced under such conditions. This sexually dimorphic immune response to hemorrhage appears to he related to high estrogen and t estosterone levels in females and males, respectively. Nonetheless, it is u nknown what impact the age-related decline in the sex steroid levels has on the immune response after hemorrhage. To study this, young (2-3 mo) and ag ed (18-19 mo) male and female CBA/J NIA mice were subjected to laparotomy ( i.e., soft tissue trauma) and hemorrhage (35 +/- 5 mmHg for 90 min and flui d resuscitation) or sham operation. Twenty-four hours later, splenocyte res ponses were assessed in vitro. Splenic T lymphocyte responses [i.e., prolif eration, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) release] wer e depressed in young males and enhanced in young females after trauma-hemor rhage. In contrast, in the aged male and female groups these parameters of splenocyte function were reversed after trauma-hemorrhage (i.e., increased proliferation and IL-2 release in aged males compared with suppressed proli feration and IFN-gamma release in aged females). Furthermore, the release o f the immunosuppressive cytokine IL-10 inversely correlated with the age- a nd gender-related changes in splenocyte responses after trauma-hemorrhage. Thus the sexually dimorphic immune response in young males and females to t rauma-hemorrhage appears to reverse as sex hormone levels decline with age.