PMID- 18447905 OWN - NLM STAT- MEDLINE DCOM- 20080626 LR - 20211020 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 8 DP - 2008 Apr 30 TI - Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats. PG - 55 LID - 10.1186/1471-2334-8-55 [doi] AB - 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 mug/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-alpha 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-alpha levels and a reduced expression of TNF-alpha 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. FAU - Bauhofer, Artur AU - Bauhofer A AD - Institute of Theoretical Surgery, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany. a-bauhofer@web.de FAU - Huttel, Markus AU - Huttel M FAU - Lorenz, Wilfried AU - Lorenz W FAU - Sessler, Daniel I AU - Sessler DI FAU - Torossian, Alexander AU - Torossian A LA - eng PT - Journal Article DEP - 20080430 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 11062-77-4 (Superoxides) RN - 140QMO216E (Metronidazole) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 74469-00-4 (Amoxicillin-Potassium Clavulanate Combination) RN - 75J73V1629 (Ceftriaxone) SB - IM MH - Amoxicillin-Potassium Clavulanate Combination/administration & dosage MH - Animals MH - Anti-Bacterial Agents/*administration & dosage MH - *Antibiotic Prophylaxis MH - Ceftriaxone/administration & dosage MH - Chemotaxis MH - Cytokines/analysis/metabolism MH - Drug Administration Schedule MH - Drug Evaluation, Preclinical MH - Drug Therapy, Combination MH - Feces/microbiology MH - Granulocyte Colony-Stimulating Factor/*administration & dosage MH - Granulocytes/*physiology MH - Injections, Intravenous MH - Injections, Subcutaneous MH - Interleukin-1/metabolism MH - Liver/immunology/metabolism MH - Male MH - Metronidazole/administration & dosage MH - Rats MH - Rats, Wistar MH - Recombinant Proteins MH - Sepsis/*immunology/*prevention & control MH - Superoxides/analysis/metabolism MH - Survival Rate MH - Tumor Necrosis Factor-alpha/biosynthesis/blood PMC - PMC2386131 EDAT- 2008/05/02 09:00 MHDA- 2008/06/27 09:00 PMCR- 2008/04/30 CRDT- 2008/05/02 09:00 PHST- 2007/10/08 00:00 [received] PHST- 2008/04/30 00:00 [accepted] PHST- 2008/05/02 09:00 [pubmed] PHST- 2008/06/27 09:00 [medline] PHST- 2008/05/02 09:00 [entrez] PHST- 2008/04/30 00:00 [pmc-release] AID - 1471-2334-8-55 [pii] AID - 10.1186/1471-2334-8-55 [doi] PST - epublish SO - BMC Infect Dis. 2008 Apr 30;8:55. doi: 10.1186/1471-2334-8-55.