Immunomodulation with granulocyte–macrophage colony-stimulating factor and interleukin 2 in an experimental model of sepsis

Abstract

Abstract Background Previous studies have demonstrated that immunomodulation with granulocyte–macrophage colony-stimulating factor (GM-CSF) reduces the mortality rate in an experimental model of sepsis, decreases levels of tumour necrosis factor in the serum and in the liver, and enhances neutrophil activity. It was also demonstrated recently that immunoprophylaxis with interleukin (IL) 2 can reduce the mortality rate in rats that have undergone caecal ligature and puncture (CLP). In fact, IL-2 is the major activator of the specific immune response (B and T lymphocytes). The aim of this study was to investigate whether IL-2 and GM-CSF together might further decrease the mortality rate in an experimental model of peritonitis in rats, which resembles the clinical situation of bowel perforation and mixed bacterial peritonitis. Methods Peritonitis was induced by CLP in four groups of Sprague–Dawley male rats (250 g). Each group included 30 rats. Group 1 underwent CLP and postoperative antibiotic therapy with tobramycin and clindamycin (12·5 μg g−1 day−1 and 4 mg g−1 day−1 respectively for 72 h after operation). Group 2 underwent preoperative intraperitoneal IL-2 injection (1.000.000 units), then CLP and postoperative antibiotic therapy with the same regimen. Group 3 underwent CLP and intraperitoneal GM-CSF injection (l ng g−1 day−1 for 48 h after operation). Group 4 received IL-2, CLP and GM-CSF with the same regimen and antibiotic therapy. Deaths were recorded within 72 h after CLP. Results After CLP group 1 (antibiotics) had a mortality rate of 70 per cent; group 4 (IL-2, GM-CSF, antibiotics) had a mortality rate of only 3 per cent which was significantly lower than in that in group 2 (IL-2 and antibiotics) and group 3 (GM-CSF and antibiotics), 33 and 25 per cent respectively (P < 0·0001). Conclusion Only one of 30 rats that had CLP and were treated with IL-2, GM-CSF and antibiotics died. Immunomodulation offers a new option in the treatment of sepsis related to peritonitis; in this experimental model treatment with IL-2 and GM-CSF enhanced host resistance to sepsis and decreased the mortality rate.