Granulocyte colony-stimulating factor and antibiotics in the prophylaxis of a murine model of polymicrobial peritonitis and sepsis.
Infections that occur after intraabdominal surgery still cause considerable morbidity and mortality despite the administration of prophylactic antibiotics. Increasing the number of neutrophils may also be a prophylactic approach, and granulocyte colony-stimulating factor (G-CSF) has been found to be beneficial in different animal models of peritonitis and sepsis. It is the combination of G-CSF and antibiotics, however, that is clinically relevant. Treatment of mice with G-CSF that was started before cecal ligation and puncture and continued afterward with antibiotics improved survival, decreased splenic bacterial colony-forming units and serum tumor necrosis factor, and increased serum interleukin-10, compared with treatment with antibiotics alone or with saline. Compared with saline, antibiotics alone increased tumor necrosis factor and did not affect interleukin-10. Thus, G-CSF confers onto antibiotics beneficial antiinfectious and antiinflammatory properties. A prophylactic regimen combining G-CSF and antibiotics may help prevent severe infectious complications following intraabdominal surgery.
Villa
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P
Mario Negri Institute for Pharmacological Research and CNR Cellular and Molecular Pharmacology Center, Milan, Italy.
Shaklee
C L
CL
Meazza
C
C
Agnello
D
D
Ghezzi
P
P
Senaldi
G
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D002432:Cecum; D002981:Clindamycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005839:Gentamicins / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D051379:Mice; D009504:Neutrophils / Q000166:cytology; D010538:Peritonitis / Q000517:prevention & control*; D018805:Sepsis / Q000517:prevention & control*; D017741:Survivors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D002981:Clindamycin; C007084:clindamycin phosphate