Mechanisms in Systemic Inflammation

Acute pancreatitis is the consequence of proteolytically induced cell death of acinar cells. The resulting damage triggers an immune response, which ultimately spreads and induces a systemic inflammatory response syndrome. The severity of the pancreatic damage is driven by necrotic cell death in the pancreas, but the systemic immune response determines morbidity and mortality. Acute pancreatitis is a primarily a sterile inflammatory response, where immune cells are activated via the release of cytokines as well as DAMPs (damage-associated molecular patterns) and start to amplify the inflammation. Since DAMPs are primarily released by necrotic cell death, there is a direct link between the local damage and the systemic immune response. Life-threatening complications such as multiple organ failure or infected pancreatic necrosis are associated with an increase in morbidity and in mortality of up to 30%. These complications are caused by an excessive immune response, which decouples the severity of pancreatitis from the local processes taking place in the pancreas. The disengaged immune response is one reason why there is no causal treatment strategy for severe acute pancreatitis, but all efforts rely on symptomatic therapies and preservation of organ function.