IFN-GAMMA DECREASES TRANSLOCATION AND IMPROVES SURVIVAL FOLLOWING TRANSFUSION AND THERMAL-INJURY

The effects of recombinant murine interferon-gamma (rmIFN-gamma) on survival and host defense were studied during gut-derived sepsis that included transfusion-induced immunosuppression. Balb/c mice (n = 153) were transfused with allogeneic blood and then treated with different doses of rmIFN-gamma: 10, 100, 1000, 10,000 U, or sterile saline as control once daily for 3 days. Five days after transfusion they were gavaged with 10(10) Escherichia coli and given a 20% TBSA burn injury. Survival was significantly higher in groups receiving 10 U compared to control and the group receiving 10,000 U (P < 0.0001 and P = 0.02, respectively). Groups receiving 100 or 1000 U also showed an improvement of survival compared to nontreated control animals (P = 0.02). The effect of rmIFN-gamma on the degree of translocation and the host's ability to kill translocated organisms was also investigated. Mice were treated as described above, except they were gavaged with In-111 oxine-labeled E. coli and then subjected to a 20% TBSA burn. Mesenteric lymph nodes (MLN), liver, and spleen were harvested aseptically. Less translocation to the liver was observed compared to the nontreated group (P = 0.002) to the MLNs and spleen of the group treated with 100 U rmIFN-gamma compared to controls and the group treated with 10 U (P < 0.005). Animals receiving 1000 U showed fewer bacteria in the liver and spleen compared to the control group (P < 0.005). Moreover, the ability to kill translocated organisms was significantly enhanced in the liver of the animals receiving 10 or 100 U rmIFN-gamma compared to all other groups (P < 0.0001). In conclusion, the study suggests that treatment with 10 and 100 U of rmIFN-gamma positively affects the outcome in gut-derived sepsis, mainly by enhancing killing of translocated bacteria. The beneficial effect in animals receiving 100 or 1000 U was related to an improved gut barrier function. (C) 1994 Academic Press, Inc.