GRANULOCYTE-COLONY-STIMULATING FACTOR PROPHYLAXIS BEFORE OPERATION PROTECTS AGAINST LETHAL CONSEQUENCES OF POSTOPERATIVE PERITONITIS

Background. Postoperative peritonitis has a high mortality in human be ings. It is accepted that cytokines are important mediators in pathoph ysiology of sepsis. The recent failure of clinical trials increased th e necessity to proof new drugs in more clinically relevant animal mode ls. The aim of this study was to examine the effect of granulocyte col ony-stimulating factor (G-CSF) in addition to an antibiotic in postope rative peritonitis. Methods. Dose-response curves and experimental con ditions were developed in a total of 295 rats. The main experiment inc luded three groups: control animals receiving a fecal inoculum, a grou p treated with antibiotic, and a third group receiving G-CSF in additi on to the antibiotic. The main outcome was death, but in addition, ser um tumor necrosis factor (TNF) level was determined. Results. The mort ality rate of 60% in antibiotic treated animals was consider-ably redu ced 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 suppressio n of TNF serum levels was accessible in contrast to the others. Conclu sions. In a clinically relevant animal model G-CSF was effective as an , additional concept of prophylaxis. These data are promising toward c linical trials.