Granulocyte macrophage colony-stimulating factor improves survival in two models of gut-derived sepsis by improving gut barrier function and modulating bacterial clearance

Objective: The effect of recombinant murine granulocyte macrophage colony- stimulating factor (rmGM-CSF) on survival and host defense was studied using two clinically relevant models of infection that included transfusion- induced immunosuppression. Summary Background Data: Granulocyte macrophage colony-stimulating factor improves resistance in several models of infection, but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. Methods: Balb/c mice were treated with 100 ng of rmGM-CSF or placebo for 6 days in a model of transfusion, burn, and gavage, or cecal ligation and puncture (CLP). Translocation was studied in the first model. Results: Survival after transfusion, burn, and gavage was 90% in rmGM-CSF-treated animals versus 35% in the control group (p < 0.001). After CLP, survival was 75% in the rmGM- CSF group versus 30% in the control group (p = 0.01). Less translocation and better killing of bacteria was observed in the tissues in animals treated with rmGM-CSF. Conclusion: The ability of rmGM-CSF to improve gut barrier function and enhance killing of translocated organisms after burn injury induced gut origin sepsis was associated with improved outcome. Granulocyte macrophage colony-stimulating factor also improved survival after CLP.