Use of in vivo caspase inhibitor in rat burn and infection injury prevents gut bacterial translocation and modulates CD4+ T cell effector immune response. (P3272)

Abstract

Abstract Our previous studies have focused on gut-associated lymphoid tissues, failure of intestinal gut barrier, bacterial translocation, and sepsis exploring the roles of antigen-presenting cells, DCs, CD4+ T cell and regulatory T cells in immunosuppression following acute burn and/or burn-plus-infection injury. In an established rodent model of burn plus infection we tested in vivo use of caspase inhibitor and studied T cell effector immune response and gut barrier function. Z-VAD-FMK, a highly specific, cell-permeable, and irreversible inhibitor of caspases was given to rats and were then assessed for mortality, bacterial translocation, T cell receptor expression and apoptosis. The results suggested an increase in CD4+CD25+ T cell phenotype in splenocytes of burn as compared to sham rats, however such an elevation in CD4+CD25+ expression was reduced in CLP and CLP+Burn+Caspase-Inhibitor groups. The results also showed that there was an increase in adhesion receptors (LFA) and decrease in CD62L in burn, whereas no difference in these adhesion receptor expressions was ascertained in Burn+CLP and Burn+CLP+Caspase-Inhibitor treated rats. A decrease in homing receptor (CD49d) was also noticed in Burn+CLP and Burn+CLP+Caspase-Inhibitor-treated animals. The Colony Forming Unit (CFU) results showed absence of bacterial translocation in rats that were subjected to burn+CLP+Caspase-Inhibitor, however there was significant bacterial translocation in rats from the group of CLP and burn only.