Gender-related therapy: early IL-10 administration after hemorrhage restores immune function in males but not in females.

Abstract

Recent experimental studies have found gender differences in the immune response after hemorrhagic shock with an enhanced immune function and lower mortality after subsequent sepsis in females than in males. Interleukin-10 (IL-10) has been shown to play a potential role in the treatment of early proinflammatory state after hemorrhagic shock. Although studies showed beneficial effects of the treatment with IL-10, it remains unclear whether the effects are gender related. To study this, male and female CBA/J mice were subjected to hemorrhage (35+/-5 mmHg for 90 min and fluid resuscitation) or sham operation. At resuscitation, each received either recombinant murine IL-10 (rmIL-10) or placebo i.p. At 48 h after resuscitation, peritoneal macrophages (pMphi) and splenocytes were harvested. IL-1beta and IL-12 release by pMphi and splenocyte proliferation and splenocyte IL-2 and interferon (IFN)-gamma release capacity were assessed. Interleukin-10 plasma levels were not increased after rmIL-10 treatment. The results indicate that rmIL-10 treatment restores depressed immune response (splenocyte proliferation, IFN-gamma, IL-1beta in males after hemorrhagic shock. In contrast, the immune responses after shock in females were not influenced by rmIL-10, with the exception of depressed splenocyte proliferation. In addition, sham-operated male mice treated with rmIL-10 showed immune depression compared with the placebo group. Thus, administration of rmIL-10 during resuscitation after hemorrhage produces salutary effects on the depressed immune responses in males but did not further enhance the immune functions in females under those conditions.