Therapeutic Role of Recombinant Human Granulocyte Colony-Stimulating Factor in Treating E. Coli Peritonitis in Rats

Minoru Kuroiwa

First Department of Surgery, Gunma University School of Medicine (Director: Prof. Yukio Nagamachi)

To investigate the therapeutic efficacy of G-CSF in treating peritonitis, we examined its effect on the mortality and function of polymorphonuclear leukocytes (PMN) in a rat peritonitis model. E. coli was administered intraperitoneally. G-CSF and/or an antibiotic (LMOX) were given to rats after the onset of peritonitis. The mortality rate was decreased by simultaneous administration of G-CSF. Moreover, the administration of G-CSF in combination with LMOX induced a marked increase in the survival rate (100%), and resutlted in improvement of the peripheral leukocyte count. The ability of PMN to generate O₂^- in the LMOX + G-CSF treated group was significantly enhanced as compared with that of the other treated groups. The plasma endothelin-1 (ET-1) level was shown to be the lowest in the group treated with LMOX + G-CSF and to correlate with a decrease in the rat mortality in contrast with the endotoxin level. The combined use of G-CSF in treatment did not induce the findings of acute lung injury. These results suggest that G-CSF may have a protective effect on survival and also provide excellent support to antibiotics in the treatment of severe peritonitis. In addition, in this series of experiments,the plasma ET-1 level, regardless of endotoxin, was a useful indicator of the severity of peritonitis.

Key words
granulocyte colony-stimulating factor (G-CSF), peritonitis, leukopenia, superoxide anion (O₂^-)

Reprint requests
Minoru Kuroiwa First Department of Surgery, Gunma University School of Medicine
3-39-15 Showamachi, Maebashi, 371 JAPAN

Accepted
November 9, 1994

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