Compartmentalization of the protease-antiprotease balance in early severe acute pancreatitis.

Objective: To assess the balance between trypsin and protease inhibitors simultaneously in the systemic circulation and in the thoracic lymph and peritoneal exudate. Methods: Twenty patients with early severe acute pancreatitis were studied. Enzymatically active and immunoreactive trypsin in conjunction with its major inhibitors were measured in the 3 compartments at the onset of end-organ failure(s). The molecular forms of trypsin were determined in the lymph and ascites by gel filtration chromatography to separate trypsinogen and free- and inhibitor-bound trypsin. Results: Both enzymatically active trypsin and immunoreactive trypsin levels were highest in ascites and lymph compared with the systemic circulation. Intracompartmental alpha(1)-protease inhibitor gradient moved in the opposite direction, whereas alpha(2) macroglobulin concentration was highest in ascites and lowest in the lymph. Although most of the enzymatically and immunoreactive material in ascites and lymph consisted of trypsin complexed with alpha(2) macroglobulin and trypsinogen, respectively, free active trypsin was detected in more than 80% of the samples. Conclusions: In patients with early severe acute pancreatitis, there is a significant trypsinogen activation resulting in protease-antiprotease imbalance and thereby free enzymatically active trypsin in the 2 body fluid compartments in close vicinity to the inflammatory process. This may be involved in the pathophysiology of local and distant tissue damage.