Novel protective effects of stem cell factor in a murine model of acute septic peritonitis - Dependence on MCP-1

Mast cells participate in the host response during sepsis and have been sho wn to have a protective effect in a murine model of acute septic peritoniti s and multi-organ failure initiated by cecal ligation and puncture (CLP). S tem cell factor (SCF) is a hematopoietic cytokine important in mast cell pr oliferation and activation. In the present study, we examined the protectiv e effects of a single Intraperitoneal injection of SCF given 2 hours before CLP surgery in mice. Four days after the CLP surgery, SCF pretreatment sig nificantly improved mouse survival from 29 to 56% and mast cells were absol utely required for this effect. Immunoneutralization studies revealed that the SCF-stimulated release of monocyte chemoattractant protein-1 (MCP-1) in to the septic peritoneal cavity contributed to the protective effect of SCF in this model One potential cellular source of MCP-1 was the SCF-activated mast cell. In addition, SCF pretreatment significantly augmented circulati ng levels of SCF and the immunomodulatory cytokine interleukin-10 in septic mice, in part because the SCF pretreatment seemed to promote the release o f both mediators from the Liver. Additional hepatic effects of SCF treatmen t included an accelerated expression of hepatic levels of signal transducer and activator of transcription-3 (STAT-S) in CLP mice pretreated with SCF, Taken together, the findings from the present study demonstrate that the i ntraperitoneal delivery of SCF has a major protective effect in a murine mo del of CLP.