Granulocyte colony-stimulating factor and neutrophil-related changes in local host defense during recovery from shock and intra-abdominal sepsis.
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 (i.e., 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.
Davis
K A
KA
Department of Surgery, University of Tennessee, Memphis, USA.
Fabian
T C
TC
Ragsdale
D N
DN
Trenthem
L L
LL
Croce
M A
MA
Proctor
K G
KG
D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006439:Hemodynamics; D009104:Multiple Trauma / Q000276:immunology / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D015427:Reperfusion Injury / Q000209:etiology; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000628:therapy*; D013552:Swine
D016179:Granulocyte Colony-Stimulating Factor