%0 Journal Article
%T Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats
%A Artur Bauhofer
%A Markus Huttel
%A Wilfried Lorenz
%A Daniel I Sessler
%A Alexander Torossian
%J BMC Infectious Diseases
%D 2008
%I BioMed Central
%R 10.1186/1471-2334-8-55
%X 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 ¦Ìg/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-¦Á and liver cytokine mRNA expression levels were determined.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-¦Á levels and a reduced expression of TNF-¦Á and IL-1 in the liver.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.Source control and antibiotic treatment are the mainstays in the treatment of infectious disease. Interestingly, antibiotics not only directly reduce bacterial growth; they also modulate cellular host defence, especially the antimicrobial functions of monocytes and granulocytes [1]. Some antibiotics enhance cellular host defence mechanisms, but others have adverse effects. How these alterations occur remains poorly understood, but cytokines and chemokines are throught to be important regulators of antimicrobial functions [2].Granulocyte colony-stimulating factor (G-CSF) is a glycopeptide which stimulates the granulocyte lineage and stem cells. G-CSF also suppresses release of pro-inflammatory cytokines such as TNF-¦Á by macro
%U http://www.biomedcentral.com/1471-2334/8/55