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For more than a century autodigestion has been regarded as the principal mechanism underlying pancreatitis.1 The modern version of this concept implies that a premature and intrapancreatic activation of pancreatic proteases occurs very early in the disease, and then overwhelms a multitude of protective mechanisms that physiologically prevent or inhibit digestive enzymes activity outside the small intestine.2 Novel treatments that target protease activity have, unfortunately, not been shown to be consistently beneficial in clinical pancreatitis. This is probably because they either target the wrong proteases or because they are administered too late in the disease process.3
Another line of experimental evidence suggests that, while initial protease activation may be a triggering event, the ultimate disease severity depends on the balance between pro- and anti-inflammatory responses of the affected patient and cellular and humoral factors have been shown to be involved in the process.4 While activities of pancreatic enzymes in the blood, ie, parameters of local damage such as amylase and lipase, can be used to determine the presence or absence of pancreatitis, they do not reflect disease severity in humans and the extent of their elevation is of no prognostic value. Parameters reflecting the inflammatory response, such as C-reactive protein, procalcitonin or polymorphonuclear (PMN)-elastase, on the other hand, have been found to correlate rather well with disease severity and are commonly used to triage patients to intensive care surveillance and treatment.5 6 Based on this “inflammation concept” of pancreatitis a number of experimental studies have been conducted in order to modulate the inflammatory response and to attain a beneficial therapeutic effect. Inhibiting pro-inflammatory mediators (eg, platelet activating factor (PAF), interleukin 6 (IL6), intracellular adhesion molecule (ICAM), S100A9, toll-like receptor 4 (TLR4)) or enhancing anti-inflammatory mechanisms (eg, IL10) or modulating cellular immune responses, have all been …
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