We tested the hypothesis that testosterone depletion or blockade in male rats protects against trauma
-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph
Male, castrated male, or flutamide-treated rats (25 mg/kg subcutaneously after resuscitation) were subjected to a laparotomy (trauma
), mesenteric lymph
duct cannulation, and 90 minutes of shock
(35 mm Hg) or trauma
. Mesenteric lymph
was collected preshock, during shock
, and postshock. Gut injury was determined at 6 hours postshock using ex vivo ileal permeability with fluorescein dextran. Postshock mesenteric lymph
was assayed for biological activity in vivo by injection into mice and measuring lung permeability, neutrophil activation, and red blood cell deformability. In vitro neutrophil priming capacity of the lymph was also tested.
Castrated and flutamide-treated male rats were significantly protected against trauma
(T/HS)-induced gut injury when compared with hormonally intact males. Postshock mesenteric lymph
from male rats had a higher capacity to induce lung injury, Neutrophil (PMN) activation, and loss of red blood cell deformability when injected into naïve mice when compared with castrated and flutamide-treated males. The increase in gut injury after T/HS in males directly correlated with the in vitro biological activity of mesenteric lymph
to prime neutrophils for an increased respiratory burst.
After T/HS, gut protective effects can be observed in males after testosterone blockade or depletion. This reduced gut injury contributes to decreased biological activity of mesenteric lymph
leading to attenuated systemic inflammation and distant organ injury.