Granulocyte colony-simulating 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 colo ny-stimulating factor (G- CSF) improves abscess localization and reduces mo rtality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to deter mine actions of G-CSF on PMN function in the peritoneum. Methods. Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation We have reported that treatment with exogenou s and incision and 35 % hemorrhage (trauma). After 1 hour thy were resuscit ated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solu tion 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 el astase 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 peri toneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytot oxicity was augmented and delayed (maximum 48 hours, P = .004). Despite the se changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMV-mediated damage in the lung as judged by bron choalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myelop eroxidase, 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 intr a-abdominal septic focus by increased production of circulating PMNs, incre ased PMN extravasation into the peritoneal cavity, and increased PMN cytoto xicity at the abdominal septic focus, without exaggerating PMN-dependent re perfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in th e multiply injured trauma patient.