Granulocyte colony-stimulating factor prophylaxis before operation protects against lethal consequences of postoperative peritonitis.
BACKGROUND
Postoperative peritonitis has a high mortality in human beings. It is accepted that cytokines are important mediators in pathophysiology of sepsis. The recent failure of clinical trials increased the necessity to proof new drugs in more clinically relevant animal models. The aim of this study was to examine the effect of granulocyte colony-stimulating factor (G-CSF) in addition to an antibiotic in postoperative peritonitis.


METHODS
Dose-response curves and experimental conditions were developed in a total of 295 rats. The main experiment included three groups: control animals receiving a fecal inoculum, a group treated with antibiotic, and a third group receiving G-CSF in addition to the antibiotic. The main outcome was death, but in addition, serum tumor necrosis factor (TNF) level was determined.


RESULTS
The mortality rate of 60% in antibiotic treated animals was considerably reduced by G-CSF to 20%. All animals of the control group died during the observation period of 120 hours. A correlation between TNF levels and mortality rate was observed. In G-CSF treated animals total suppression of TNF serum levels was accessible in contrast to the others.


CONCLUSIONS
In a clinically relevant animal model G-CSF was effective as an additional concept of prophylaxis. These data are promising toward clinical trials.
Lorenz
W
W
Department of General Surgery, University of Marburg, Germany.
Reimund
K P
KP
Weitzel
F
F
Celik
I
I
Kurnatowski
M
M
Schneider
C
C
Mannheim
W
W
Heiske
A
A
Neumann
K
K
Sitter
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D005243:Feces / Q000382:microbiology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D010538:Peritonitis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D011183:Postoperative Complications / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D011292:Premedication; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor