Remote Pancreatic Response to Severe Polytrauma Correlates With Clinical Outcome.

BACKGROUND: Acute pancreatic injury can result from blunt or sharp force trauma, often leading to serious complications. While direct pancreatic trauma is associated with high rates of infection, organ failure, and mortality, little is known about the pancreas as a potential secondary target and remote trauma organ and thereby as a booster of systemic injury. METHODS: We employed a murine model of multiple trauma and hemorrhagic shock in which the pancreas was deliberately spared from the direct trauma impact. Four hours post-trauma, we determined systemic and local inflammatory responses, pancreatic tissue damage, pancreatic lipase (Pnlip in mice), and protease activity, and conducted proteomic profiling of the pancreas. For clinical translation, we performed a post hoc analysis of severely injured polytrauma patients, focusing on acute pancreatic involvement and its association with clinical parameters. RESULTS: Severe trauma in mice induced rapid systemic inflammation and significantly elevated plasma levels of Pnlip. Notably, pancreatic edema formation was observed in a subset of polytraumatized mice, accompanied by increased activity of matrix metalloproteinases Mmp2 and Mmp9. Proteomic analysis revealed an enrichment of inflammatory and cellular stress pathways in pancreatic tissue. Similarly, in polytraumatized patients, plasma pancreatic lipase (PNLIP in humans) and trypsin concentrations were elevated during the early posttraumatic period and correlated with injury patterns, systemic inflammation, coagulopathy, endotheliopathy, organ failure, and time in hospitals and intensive care units. CONCLUSION: Our findings highlight the pancreas as a novel remote responder to severe tissue trauma, even in the absence of direct injury. This widely overlooked dimension of trauma pathophysiology has potential clinical implications. However, further research is essential (i) to unravel the mechanisms driving remote pancreatic enzyme release and (ii) to prove the causality between the pancreatic response and observed clinical parameters.