Severe acute pancreatitis between systematic inflammatory response syndrome and sepsis: insights from a mathematical model of endotoxin tolerance

In order to evaluate the degree of endotoxin tolerance, expressed by the reduced cytokine/releasing capacity of the whole blood, data from a group of patients with trauma, severe acute pancreatitis (SAP), and diffuse peritonitis were analyzed. In SAP endotoxin levels and the tumor necrosing factor (TNF-α)–releasing capacity of the whole blood under lipopolysaccharide (LPS) stimulation were of an intermediate degree between systemic inflammatory response syndrome and severe sepsis. A mathematical model of ordinary differential equations of LPS signaling based on endotoxin kinetics and endotoxin tolerance was constructed. The mathematical model was used to reproduce the TNF-α production in trauma, SAP and peritonitis patients. The results of these numerical simulations are very similar to the determinations in real patients and argue that endotoxin tolerance may be a component of the immune dysregulation that complicates the clinical evolution of the patient with SAP.