Abstract
Severe acute pancreatitis (SAP) starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT) during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly) gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS) can lead to multiple organ dysfunction syndrome (MODS) during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs) are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.
Highlights
Acute pancreatitis (AP) is a relatively common disease, its severe form is potentially fatal, and Severe acute pancreatitis (SAP) is associated with high mortality, ranging from 15 to 40% [1,2,3,4,5,6,7,8]
AP starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction including acute lung injury [8,9,10], general endothelial barrier dysfunction, liver injury, and gut barrier dysfunction [2, 6, 8]; systemic inflammation is thought to be the key link to multiple organ dysfunction (MOD) in SAP [11, 12] and gut bacterial translocation (BT) plays a critical role in triggering/inducing systemic inflammation [13, 14]; the underlying mechanism of BT in SAP is still poorly understood
The inflammatory cytokines play a crucial role in the pathogenesis of SAP [6, 7, 15, 16] and the late proinflammatory cytokine HMGB1 is important in SAP [17, 18], because the circulating HMGB1 levels can reflect the disease severity and are potent in augmenting systemic inflammation [17, 18], and emerging evidence shows that HMGB1 is an important factor that mediates 85% of the gut BT in acetaminophen hepatotoxicity [19]; it is possible that HMGB1 mediates BT in SAP
Summary
Acute pancreatitis (AP) is a relatively common disease, its severe form is potentially fatal, and SAP is associated with high mortality, ranging from 15 to 40% [1,2,3,4,5,6,7,8]. Except HMGB1, new investigations show that extracellular histones and DNAs might significantly contribute to multiple organ injury during SAP [20,21,22,23].
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