Research article

Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats

Artur Bauhofer^1,4 , Markus Huttel¹ , Wilfried Lorenz¹ , Daniel I Sessler² and Alexander Torossian³

¹Institute of Theoretical Surgery, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany

²Department of Outcomes Research, The Cleveland Clinic, Cleveland, OH 44195, USA

³Clinic of Anesthesiology and Critical Care, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany

⁴MEDA Pharma GmbH & Co KG, Benzstrasse 1, 61352 Bad Homburg, Germany

author email corresponding author email

BMC Infectious Diseases 2008, 8:55doi:10.1186/1471-2334-8-55

Published:	30 April 2008

Abstract

Background

In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF.

Methods

In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 μg/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-α and liver cytokine mRNA expression levels were determined.

Results

Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-α levels and a reduced expression of TNF-α and IL-1 in the liver.

Conclusion

There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response.