OBJECTIVE: To study the therapeutic effect of granulocyte colony-stimulating factor (G-CSF) on the mortality rate and host defense pattern in fulminant intra-abdominal sepsis. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Fulminant polymicrobial intra-abdominal sepsis was induced by a 4-mm cecal perforation. Survival experiments were performed with two different doses of G-CSF (20 and 100 microg/kg/24 hrs), and therapy was started 7 days or 1 day before, or 4 hrs after sepsis induction (n = 24). To examine alterations in host response pattern, G-CSF (20 microg/kg/24 hrs) was given at sepsis induction, and rats were killed 4, 8, 12 and 24 hrs later (n = 8-16 per time period). Histologic examination of lung, liver, spleen, and kidney was performed, and blood concentrations of bacteria, endotoxin, tumor necrosis factor (TNF), endothelin-1, packed cell volume, and lactate were determined. MEASUREMENTS AND MAIN RESULTS: G-CSF (20 microg/kg/24 hrs), given 4 hrs after sepsis induction, reduced the mortality rate from 96% to 42%. Increasing the dose (100 micrograms/kg/24 hrs), or giving G-CSF as prophylaxis (starting 7 days or 1 day before sepsis), gave no further protection. G-CSF attenuated the sepsis-induced enhancement of circulating bacteria, endotoxin, TNF, and endothelin-1, resulting in improved fluid balance and reduced lactate concentration. No histopathologic alterations were observed after G-CSF treatment. CONCLUSIONS: G-CSF improves host defense and survival rate in experimentally induced fulminant intra-abdominal sepsis. Clearance of bacteria and endotoxin is improved, concentrations of TNF and endothelin-1 are suppressed, and microvascular flow is improved. G-CSF does not induce neutrophil-mediated tissue damage.
OBJECTIVE: To study the therapeutic effect of granulocyte colony-stimulating factor (G-CSF) on the mortality rate and host defense pattern in fulminant intra-abdominal sepsis. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Fulminant polymicrobial intra-abdominal sepsis was induced by a 4-mm cecal perforation. Survival experiments were performed with two different doses of G-CSF (20 and 100 microg/kg/24 hrs), and therapy was started 7 days or 1 day before, or 4 hrs after sepsis induction (n = 24). To examine alterations in host response pattern, G-CSF (20 microg/kg/24 hrs) was given at sepsis induction, and rats were killed 4, 8, 12 and 24 hrs later (n = 8-16 per time period). Histologic examination of lung, liver, spleen, and kidney was performed, and blood concentrations of bacteria, endotoxin, tumor necrosis factor (TNF), endothelin-1, packed cell volume, and lactate were determined. MEASUREMENTS AND MAIN RESULTS:G-CSF (20 microg/kg/24 hrs), given 4 hrs after sepsis induction, reduced the mortality rate from 96% to 42%. Increasing the dose (100 micrograms/kg/24 hrs), or giving G-CSF as prophylaxis (starting 7 days or 1 day before sepsis), gave no further protection. G-CSF attenuated the sepsis-induced enhancement of circulating bacteria, endotoxin, TNF, and endothelin-1, resulting in improved fluid balance and reduced lactate concentration. No histopathologic alterations were observed after G-CSF treatment. CONCLUSIONS:G-CSF improves host defense and survival rate in experimentally induced fulminant intra-abdominal sepsis. Clearance of bacteria and endotoxin is improved, concentrations of TNF and endothelin-1 are suppressed, and microvascular flow is improved. G-CSF does not induce neutrophil-mediated tissue damage.
Authors: M Nadai; I Matsuda; L Wang; A Itoh; K Naruhashi; T Nabeshima; M Asai; T Hasegawa Journal: Antimicrob Agents Chemother Date: 1998-09 Impact factor: 5.191
Authors: K Reinhart; F Brunkhorst; H Bone; H Gerlach; M Gründling; G Kreymann; P Kujath; G Marggraf; K Mayer; A Meier-Hellmann; C Peckelsen; C Putensen; M Quintel; M Ragaller; R Rossaint; F Stüber; N Weiler; T Welte; K Werdan Journal: Internist (Berl) Date: 2006-04 Impact factor: 0.743
Authors: K Reinhart; F M Brunkhorst; H-G Bone; J Bardutzky; C-E Dempfle; H Forst; P Gastmeier; H Gerlach; M Gründling; S John; W Kern; G Kreymann; W Krüger; P Kujath; G Marggraf; J Martin; K Mayer; A Meier-Hellmann; M Oppert; C Putensen; M Quintel; M Ragaller; R Rossaint; H Seifert; C Spies; F Stüber; N Weiler; A Weimann; K Werdan; T Welte Journal: Ger Med Sci Date: 2010-06-28
Authors: Artur Bauhofer; Alexander Torossian; Wilfried Lorenz; Martin Middeke; Ulrike Plaul; Philipp Schütz; Benno Stinner; Markus Hattel; Ilhan Celik Journal: World J Surg Date: 2004-08-03 Impact factor: 3.352
Authors: Alieke G Vonk; Mihai G Netea; Johan H van Krieken; Paul E Verweij; Jos W M van der Meer; Bart Jan Kullberg Journal: Antimicrob Agents Chemother Date: 2003-12 Impact factor: 5.191