PGE(2) suppresses intestinal T cell function in thermal injury: A cause ofenhanced bacterial translocation

Increased gut bacterial translocation in burn and trauma patients has been demonstrated in a number of previous studies, however, the mechanism for su ch an increased gut bacterial translocation in injured patients remains poo rly understood. Utilizing a rat model of burn injury, in the present study we examined the role of intestinal immune defense by analyzing the T cell f unctions. We investigated if intestinal T cells dysfunction contributes to bacterial translocation after burn injury. Also our study determined if bur n-mediated alterations in intestinal T cell functions are related to enhanc ed release of PGE(2). Finally, we examined whether or not burn-related alte rations in intestinal T cell function are due to inappropriate activation o f signaling molecule P59(fyn), which is required for T cell activation and proliferation. The results presented here showed an increase in gut bacteri al accumulation in mesenteric lymph nodes after thermal injury. This was ac companied by a decrease in the intestinal T cell proliferative responses. F urthermore, the treatments of burn-injured animals with PGE(2) synthesis bl ocker (indomethacin or NS398) prevented both the decrease in intestinal T c ell proliferation and enhanced bacterial translocation. Finally, our data s uggested that the inhibition of intestinal T cell proliferation could resul t via PGE(2)-mediated down-regulation of the T cell activation-signaling mo lecule P59(fyn). These findings support a role of T cell-mediated immune de fense against bacterial translocation in burn injury.