Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage

Joe H. Patton, Sean P. Lyden, D. Nicholas Ragsdale, Martin A. Croce, Timothy C. Fabian, Kenneth G Proctor

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, GCSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve longterm outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Methods: Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 μg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observ- ers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro(lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Results: Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Conclusions: Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

Original languageEnglish
Pages (from-to)750-759
Number of pages10
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume44
Issue number5
DOIs
StatePublished - May 1 1998
Externally publishedYes

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Granulocyte Colony-Stimulating Factor
Shock
Sepsis
Neutrophils
Bronchoalveolar Lavage
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Placebos
Reperfusion Injury
Resuscitation
Peroxidase
Wounds and Injuries
Cell Count
Lung
Respiratory Burst
Blood Cell Count
Lung Injury
Therapeutic Uses
Tetradecanoylphorbol Acetate
Infection

ASJC Scopus subject areas

  • Surgery

Cite this

Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage. / Patton, Joe H.; Lyden, Sean P.; Ragsdale, D. Nicholas; Croce, Martin A.; Fabian, Timothy C.; Proctor, Kenneth G.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 44, No. 5, 01.05.1998, p. 750-759.

Research output: Contribution to journalArticle

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title = "Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage",
abstract = "Background: Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, GCSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve longterm outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Methods: Anesthetized swine were subjected to cecal ligation and incision, 35{\%} hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 μg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observ- ers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro(lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Results: Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50{\%}, lipopolysaccharide-tumor necrosis factor decreased by 50{\%}, and improved survival versus placebo (100{\%} vs. 70{\%}). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Conclusions: Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.",
author = "Patton, {Joe H.} and Lyden, {Sean P.} and Ragsdale, {D. Nicholas} and Croce, {Martin A.} and Fabian, {Timothy C.} and Proctor, {Kenneth G}",
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T1 - Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage

AU - Patton, Joe H.

AU - Lyden, Sean P.

AU - Ragsdale, D. Nicholas

AU - Croce, Martin A.

AU - Fabian, Timothy C.

AU - Proctor, Kenneth G

PY - 1998/5/1

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N2 - Background: Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, GCSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve longterm outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Methods: Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 μg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observ- ers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro(lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Results: Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Conclusions: Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

AB - Background: Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, GCSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve longterm outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Methods: Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 μg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observ- ers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro(lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Results: Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Conclusions: Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

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