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.


BACKGROUND
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.


CONCLUSIONS
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.
Gennari
R
R
Department of Surgery, University of Cincinnati, Ohio.
Alexander
J W
JW
Gianotti
L
L
Eaves-Pyles
T
T
Hartmann
S
S
D000818:Animals; D001803:Blood Transfusion; D002056:Burns / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D002465:Cell Movement / Q000187:drug effects; D015169:Colony Count, Microbial; D004926:Escherichia coli / Q000254:growth & development / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D007108:Immune Tolerance / Q000187:drug effects; D007410:Intestinal Diseases / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008954:Models, Biological; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D015996:Survival Rate
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor