Granulocyte colony-stimulating factor and neutrophil-related changes in local host defense during recovery from shock and intra-abdominal sepsis

Kimberly A. Davis, Timothy C. Fabian, D. Nicholas Ragsdale, Lisa L. Trenthem, Martin A. Croce, Kenneth G Proctor

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum. Methods. Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35% hemorrhage (trauma). After 1 hour they were resuscitated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solution vehicle (n = 9). The animals were observed for 72 hours. Results. After trauma, saline solution treatment increased PMN infiltration into the peritoneum within 2 hours (P = .035), increased peritoneal PMN elastase production (ie, cytotoxicity) by 24 hours (P = .004), and decreased adherence of peritoneal PMNs to an artificial substrate from 4 to 72 hrs (P = .043). The mean autopsy score was 7.0 ± 0.5. With G-CSF treatment peritoneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytotoxicity was augmented and delayed (maximum 48 hours, P = .004). Despite these changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMN-mediated damage in the lung as judged by bronchoalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myeloperoxidase, or histologic changes. The mean autopsy score was improved to 4.1 ± 0.3 (P < .001). Conclusions. G-CSF in resuscitation fluids improved localization of an intra-abdominal septic focus by increased production of circulating PMNs, increased PMN extravasation into the peritoneal cavity, and increased PMN cytotoxicity at the abdominal septic focus, without exaggerating PMN-dependent reperfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in the multiply injured trauma patient.

Original languageEnglish
Pages (from-to)305-313
Number of pages9
JournalSurgery
Volume126
Issue number2
DOIs
StatePublished - Aug 23 1999
Externally publishedYes

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Granulocyte Colony-Stimulating Factor
Shock
Sepsis
Neutrophils
Peritoneum
Wounds and Injuries
Bronchoalveolar Lavage
Reperfusion Injury
Sodium Chloride
Resuscitation
Lung
Autopsy
Leukocyte Elastase
Peritoneal Cavity
Abscess
Peroxidase
Ligation
Swine
Therapeutics
Hemorrhage

ASJC Scopus subject areas

  • Surgery

Cite this

Granulocyte colony-stimulating factor and neutrophil-related changes in local host defense during recovery from shock and intra-abdominal sepsis. / Davis, Kimberly A.; Fabian, Timothy C.; Ragsdale, D. Nicholas; Trenthem, Lisa L.; Croce, Martin A.; Proctor, Kenneth G.

In: Surgery, Vol. 126, No. 2, 23.08.1999, p. 305-313.

Research output: Contribution to journalArticle

Davis, Kimberly A. ; Fabian, Timothy C. ; Ragsdale, D. Nicholas ; Trenthem, Lisa L. ; Croce, Martin A. ; Proctor, Kenneth G. / Granulocyte colony-stimulating factor and neutrophil-related changes in local host defense during recovery from shock and intra-abdominal sepsis. In: Surgery. 1999 ; Vol. 126, No. 2. pp. 305-313.
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abstract = "Background. We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum. Methods. Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35{\%} hemorrhage (trauma). After 1 hour they were resuscitated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solution vehicle (n = 9). The animals were observed for 72 hours. Results. After trauma, saline solution treatment increased PMN infiltration into the peritoneum within 2 hours (P = .035), increased peritoneal PMN elastase production (ie, cytotoxicity) by 24 hours (P = .004), and decreased adherence of peritoneal PMNs to an artificial substrate from 4 to 72 hrs (P = .043). The mean autopsy score was 7.0 ± 0.5. With G-CSF treatment peritoneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytotoxicity was augmented and delayed (maximum 48 hours, P = .004). Despite these changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMN-mediated damage in the lung as judged by bronchoalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myeloperoxidase, or histologic changes. The mean autopsy score was improved to 4.1 ± 0.3 (P < .001). Conclusions. G-CSF in resuscitation fluids improved localization of an intra-abdominal septic focus by increased production of circulating PMNs, increased PMN extravasation into the peritoneal cavity, and increased PMN cytotoxicity at the abdominal septic focus, without exaggerating PMN-dependent reperfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in the multiply injured trauma patient.",
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AU - Davis, Kimberly A.

AU - Fabian, Timothy C.

AU - Ragsdale, D. Nicholas

AU - Trenthem, Lisa L.

AU - Croce, Martin A.

AU - Proctor, Kenneth G

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N2 - Background. We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum. Methods. Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35% hemorrhage (trauma). After 1 hour they were resuscitated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solution vehicle (n = 9). The animals were observed for 72 hours. Results. After trauma, saline solution treatment increased PMN infiltration into the peritoneum within 2 hours (P = .035), increased peritoneal PMN elastase production (ie, cytotoxicity) by 24 hours (P = .004), and decreased adherence of peritoneal PMNs to an artificial substrate from 4 to 72 hrs (P = .043). The mean autopsy score was 7.0 ± 0.5. With G-CSF treatment peritoneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytotoxicity was augmented and delayed (maximum 48 hours, P = .004). Despite these changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMN-mediated damage in the lung as judged by bronchoalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myeloperoxidase, or histologic changes. The mean autopsy score was improved to 4.1 ± 0.3 (P < .001). Conclusions. G-CSF in resuscitation fluids improved localization of an intra-abdominal septic focus by increased production of circulating PMNs, increased PMN extravasation into the peritoneal cavity, and increased PMN cytotoxicity at the abdominal septic focus, without exaggerating PMN-dependent reperfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in the multiply injured trauma patient.

AB - Background. We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum. Methods. Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35% hemorrhage (trauma). After 1 hour they were resuscitated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solution vehicle (n = 9). The animals were observed for 72 hours. Results. After trauma, saline solution treatment increased PMN infiltration into the peritoneum within 2 hours (P = .035), increased peritoneal PMN elastase production (ie, cytotoxicity) by 24 hours (P = .004), and decreased adherence of peritoneal PMNs to an artificial substrate from 4 to 72 hrs (P = .043). The mean autopsy score was 7.0 ± 0.5. With G-CSF treatment peritoneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytotoxicity was augmented and delayed (maximum 48 hours, P = .004). Despite these changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMN-mediated damage in the lung as judged by bronchoalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myeloperoxidase, or histologic changes. The mean autopsy score was improved to 4.1 ± 0.3 (P < .001). Conclusions. G-CSF in resuscitation fluids improved localization of an intra-abdominal septic focus by increased production of circulating PMNs, increased PMN extravasation into the peritoneal cavity, and increased PMN cytotoxicity at the abdominal septic focus, without exaggerating PMN-dependent reperfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in the multiply injured trauma patient.

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