Enhancement of peritoneal leukocyte function by granulocyte colony-stimulating factor in rats with abdominal sepsis

Crit Care Med. 1998 Feb;26(2):315-21. doi: 10.1097/00003246-199802000-00035.


Objective: To investigate the therapeutic effects of granulocyte colony-stimulating factor (G-CSF) on the functional activities of circulating and peritoneal neutrophils during intra-abdominal sepsis.

Design: Placebo, controlled study, using a rat model of intra-abdominal sepsis.

Setting: Animal research facility.

Subjects: Male specific pathogen-free Sprague-Dawley rats.

Interventions: Abdominal sepsis was produced in rats by cecal ligation and puncture. The control animals received a sham operation. G-CSF (subcutaneous injection at 50 microg/kg) or vehicle (100 microL of 5% dextrose) treatment was initiated at 1 hr after cecal ligation and puncture or sham operation and repeated at 12-hr intervals thereafter.

Measurements and main results: Six hours after cecal ligation and puncture, CD11b/c and CD18 expression on circulating neutrophils was significantly up-regulated when compared with those in the sham operated control animals. Peritoneal neutrophils exhibited a further up-regulation of these adhesion molecules than did the circulating neutrophils. A sustained up-regulation of CD11b/c and CD18 was found in peritoneal neutrophils even at 24 hrs after cecal ligation and puncture. G-CSF treatment increased CD11b/c expression on circulating neutrophils in 6-hr sham-operated rats, but did not further up-regulate CD11b/c or CD18 expression on circulating or peritoneal neutrophils in cecal ligation and puncture rats. Phagocytic activities of circulating neutrophils assessed by uptake of fluorescent latex microspheres were lower in 24-hr cecal ligation and puncture rats when compared with the sham-operated controls. G-CSF treatment prevented this inhibition. Furthermore, G-CSF enhanced the phagocytic activities of peritoneal neutrophils in both 6- and 24-hr cecal ligation and puncture rats when compared with those of the vehicle-treated animals. Spontaneous hydrogen peroxide generation by circulating neutrophils was increased in 6-hr cecal ligation and puncture rats, but not in 24-hr cecal ligation and puncture rats. Peritoneal neutrophils exhibited an inhibition of phorbol myristate acetate-stimulated hydrogen peroxide generation. G-CSF treatment did not up-regulate neutrophil hydrogen peroxide generation.

Conclusions: Circulating and peritoneal neutrophils exhibit marked polymorphism in their functional activities during the host response to abdominal sepsis. G-CSF treatment significantly enhanced the phagocytic function of both circulating and peritoneal neutrophils which may be one mechanism underlying its protective effect in abdominal sepsis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abdomen
  • Animals
  • CD18 Antigens / analysis
  • CD18 Antigens / drug effects
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Integrin alphaXbeta2 / analysis
  • Integrin alphaXbeta2 / drug effects
  • Macrophage-1 Antigen / analysis
  • Macrophage-1 Antigen / drug effects
  • Male
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Peritoneal Cavity / cytology*
  • Phagocytosis / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Sepsis / immunology
  • Sepsis / therapy*
  • Specific Pathogen-Free Organisms
  • Time Factors


  • CD18 Antigens
  • Integrin alphaXbeta2
  • Macrophage-1 Antigen
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor