• Leigh Willoughby, Paul Dark, and Geoffrey Warhurst.
• Infection, Injury and Inflammation Research Group, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre and School of Translational Medicine, University of Manchester, Manchester, United Kingdom.
• Shock. 2011 Aug 1;36(2):121-7.

AbstractEvidence from animal models of trauma and hemorrhage has suggested that the gut plays an active role in the pathogenesis of systemic inflammatory responses and multiple organ dysfunction syndrome. The aim of the present study was to seek evidence for gut-derived signals in man in a group of eight patients undergoing elective abdominal aortic reconstruction, a procedure that is associated with sterile tissue injury, controlled colonic ischemia as a consequence of aortic cross-clamping, and a significant risk of developing systemic inflammation and multiple organ dysfunction syndrome. Despite the presence of a marked systemic inflammatory response (IL-6, IL-18, monocyte chemoattractant protein 1, and IL-8) and a gut-derived inflammatory signal (IL-6), we could find no evidence that gut-derived pathogen DNA was present in the central or mesenteric circulation, and we could find no evidence that either central or mesenteric plasma samples could induce apoptotic or necrotic cell death in human umbilical vein endothelial cells in vitro. Similarly, we could find no evidence of adhesion molecule upregulation in the endothelial monolayers exposed to central or mesenteric plasma sampled at any time point during surgery. There was, however, evidence of an increase in the expression of RAGE (receptor for advanced glycation end products) by endothelial cells following exposure to mesenteric venous, but not central, plasma sampled during maximum ischemia. In conclusion, during sterile tissue injury and controlled colonic ischemia-reperfusion in man, there is a marked systemic proinflammatory response, which is in part gut derived, in the absence of evidence for the presence of toxic endothelial factors or gut-derived microorganisms in the central or mesenteric circulations.

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