The magnitude of increase reflected the severity of inflammation and has been associated with adverse outcomes such as disseminated intravascular coagulation, multiple organ failure and infant death. Thus, the marked up-regulation of IL-6 and other pro-inflammatory mediators could provide an explanation for the substantially higher mortality in NEC compared with SIP infants. It has also been suggested that the imbalance of proinflammatory to anti-inflammatory cytokines such as a persistently high IL6/IL-10 ratio could predict increased mortality of critically ill adult and neonatal patients. We analyzed this ratio in both NEC and SIP infants and demonstrated that a nonsignificant trend existed between those who survived and died. It is envisaged that a larger sample size with longitudinal monitoring would be required to fully address the prognostic value of IL-6/IL-10 ratio in surgical infants. IL-6 has been reported to regulate the severity of LPSdriven pro-inflammatory responses via STAT3 and cross-talk between JAK/STAT and toll-like GSK212 MEK inhibitor receptor pathways. PAF induced expression of IL-6 was also observed in different cellular systems including adult leukocytes, endothelial cells and gut mucosa in a rat model of intestinal damage. Upregulation of IL-6 mRNA was detected in resected tissues from NEC patients, but not in FHs-74 Int enterocytes upon in vitro stimulation by LPS and PAF. This observation suggests possible presence of multiple cellular sources of IL-6 production such as endothelial cells and infiltrated leukocytes in inflammed bowel tissues. Ang-2, an endothelium-specific growth factor, is known to be upregulated in sepsis and inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis in adults. Ang-2 is involved in angiogenesis and plays a key role in the pathogenesis of IBD. It is positively associated with pro-inflammatory mediators IL-6, IL-8 and TNF-a in septic patients. Ang-2 disrupts vascular quiescence by antagonizing the protective Tie-2 signaling, resulting in vascular leakage. Ang-2 also activates neutrophils and enhances PAF synthesis in human endothelial cells. We speculate that Ang-2 may further aggravate the inflammatory cascade and contribute to the pathophysiology of NEC by destabilizing vascular endothelium and increasing vascular leakage. ErbB3 is expressed in epithelial cells throughout the gastrointestinal tract and sErbB3 is the secreted form of ErbB3 receptor. ErbB3 binds to the ligand, heregulin and blocks it from binding to the cell surface receptor for induction of cell proliferation and differentiation. To date, most studies have associated ErbB3 and sErbB3 with breast and prostate cancers and there has been no report coupling these mediators with systemic inflammatory or gastrointestinal diseases in human. In SIP infants, sErbB3 might inhibit ErbB3 receptor activation on intestinal epithelial cells, thereby limiting cell proliferation and differentiation. This could potentially increase the risk of intestinal perforation. sIL-1RII is an IL-1b scavenger which negatively regulates the pro-inflammatory signals of IL-1. sIL-1RII is known to be elevated in plasma of septic patients, especially the critically-ill. LPS, TNF-a and other chemoattractants could mediate the release of sIL-1RII. It has been suggested that local shedding of sIL-1RII may decrease colonic inflammation in Crohn’s disease.