Granulocyte colony-stimulating factor prophylaxis improves survival and inflammation in a two-hit model of hemorrhage and sepsis
OBJECTIVE: We evaluated the effects of a granulocyte-colony stimulating factor (G-CSF) prophylaxis in two clinically relevant situations, hemorrhage on the day before infection (e.g., trauma) and acute hemorrhage followed subsequently by infection (e.g., operative complication). A two-hit model of hemorrhage and polymicrobial peritoneal contamination and infection (PCI) was used to assess the influence of G-CSF on the outcome, bacterial clearance, and cytokine pattern.
DESIGN: Clinic modeling randomized laboratory trial.
SETTING: University laboratory.
SUBJECTS: One hundred thirty-two male rats.
INTERVENTIONS: In trial 1 we compared a) preoperative PCI only; b) preoperative hemorrhage plus PCI; and c) hemorrhage plus PCI plus G-CSF prophylaxis (n=18 rats/group). In trial 2, intraoperative hemorrhage was assessed with the same trial design. Primary end point was survival at 120 hrs. In trial 2 additionally, six rats per group and six naive control rats were used for secondary end point analysis.
MEASUREMENTS AND MAIN RESULTS: Primary end point was mortality at 120 hrs. Secondary end points were granulocyte counts, bacterial clearance, and local cytokine levels. In trial 1 survival rate was 56% after PCI only, 17% after hemorrhage plus PCI, and 61% after hemorrhage plus PCI plus G-CSF (p<.01). In trial 2 survival rate was 33% after PCI only, 17% after hemorrhage plus PCI, and 50% after hemorrhage plus PCI plus G-CSF (p<.05). In trial 2, neutrophil counts were doubled to 66% 1 hr after hemorrhage (p<.05), colony-forming units of microbes in the lung and liver were halved to 166+/-56 and 134+/-28 colony-forming units (p<.05 for liver), and the macrophage inflammatory protein-2 expression in the lung was halved to 0.88+/-0.06 pg of complementary DNA (p<.05) by G-CSF prophylaxis compared with hemorrhage and PCI.
CONCLUSIONS: Hemorrhage (first hit) sensitized the host for a second hit of polymicrobial PCI independent of the timing. G-CSF prophylaxis improved survival and clearance of microbes and reduced the proinflammatory chemokine macrophage inflammatory protein-2 in the lung.
| Errataetall: |
CommentIn: Crit Care Med. 2006 Mar;34(3):921-3. - PMID 16505687 |
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| Medienart: |
Artikel |
| Erscheinungsjahr: |
2006 |
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| Erschienen: |
2006 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Critical care medicine - 34(2006), 3 vom: 04. März, Seite 778-84 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bauhofer, Artur [VerfasserIn] |
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| Themen: |
143011-72-7 |
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| Anmerkungen: |
Date Completed 10.04.2006 Date Revised 30.03.2022 published: Print CommentIn: Crit Care Med. 2006 Mar;34(3):921-3. - PMID 16505687 Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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NLM161123643 |
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| 245 | 1 | 0 | |a Granulocyte colony-stimulating factor prophylaxis improves survival and inflammation in a two-hit model of hemorrhage and sepsis |
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| 500 | |a CommentIn: Crit Care Med. 2006 Mar;34(3):921-3. - PMID 16505687 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: We evaluated the effects of a granulocyte-colony stimulating factor (G-CSF) prophylaxis in two clinically relevant situations, hemorrhage on the day before infection (e.g., trauma) and acute hemorrhage followed subsequently by infection (e.g., operative complication). A two-hit model of hemorrhage and polymicrobial peritoneal contamination and infection (PCI) was used to assess the influence of G-CSF on the outcome, bacterial clearance, and cytokine pattern | ||
| 520 | |a DESIGN: Clinic modeling randomized laboratory trial | ||
| 520 | |a SETTING: University laboratory | ||
| 520 | |a SUBJECTS: One hundred thirty-two male rats | ||
| 520 | |a INTERVENTIONS: In trial 1 we compared a) preoperative PCI only; b) preoperative hemorrhage plus PCI; and c) hemorrhage plus PCI plus G-CSF prophylaxis (n=18 rats/group). In trial 2, intraoperative hemorrhage was assessed with the same trial design. Primary end point was survival at 120 hrs. In trial 2 additionally, six rats per group and six naive control rats were used for secondary end point analysis | ||
| 520 | |a MEASUREMENTS AND MAIN RESULTS: Primary end point was mortality at 120 hrs. Secondary end points were granulocyte counts, bacterial clearance, and local cytokine levels. In trial 1 survival rate was 56% after PCI only, 17% after hemorrhage plus PCI, and 61% after hemorrhage plus PCI plus G-CSF (p<.01). In trial 2 survival rate was 33% after PCI only, 17% after hemorrhage plus PCI, and 50% after hemorrhage plus PCI plus G-CSF (p<.05). In trial 2, neutrophil counts were doubled to 66% 1 hr after hemorrhage (p<.05), colony-forming units of microbes in the lung and liver were halved to 166+/-56 and 134+/-28 colony-forming units (p<.05 for liver), and the macrophage inflammatory protein-2 expression in the lung was halved to 0.88+/-0.06 pg of complementary DNA (p<.05) by G-CSF prophylaxis compared with hemorrhage and PCI | ||
| 520 | |a CONCLUSIONS: Hemorrhage (first hit) sensitized the host for a second hit of polymicrobial PCI independent of the timing. G-CSF prophylaxis improved survival and clearance of microbes and reduced the proinflammatory chemokine macrophage inflammatory protein-2 in the lung | ||
| 650 | 4 | |a Evaluation Study | |
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| 700 | 1 | |a Kohlert, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a Torossian, Alexander |e verfasserin |4 aut | |
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