Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications

Abstract

Background-The time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown. Patients and methods-In a prospective clinical study, we measured the proinflammatory cytokines interleukin (IL)-1 , IL-6 and IL-8, the anti-inflammatory cytokine IL-10, interleukin 1 receptor antagonist (IL-1RA), and the soluble IL-2 receptor (sIL-2R), and correlated our findings with organ and systemic complications in acute pancreatitis. In 51 patients with acute pancreatitis admitted within 72 hours after the onset of symptoms, these parameters were measured daily for seven days. In addition, 33 aspirates from ascites and the lesser sac were measured. Results-Sixteen patients had mild acute pancreatitis (AP) and 35 severe AP (Atlanta classification); 18 patients developed systemic complications requiring treatment. All mediators were increased in AP. sIL-2R, IL-10, and IL-6 were significantly elevated in patients with distant organ failure. An imbalance in IL-1 / IL-1RA was found in severe AP and pulmonary failure. Peak serum sIL-2R predicted lethal outcome and IL-1RA was an early marker of severity. IL-6 was the best prognostic parameter for pulmonary failure. Conclusion-Our results suggest that local mediator release, with a probable IL-1 -IL-1RA imbalance in severe cases, is followed by the systemic appearance of pro-and anti-inflammatory mediators. The pattern of local and systemic mediators in complicated AP suggests a role for systemic lymphocyte activation (triggered by local release of mediators) in distant organ complications in severe AP. (Gut 2000;47:546-552)

Admission Hematocrit and Rise in Blood Urea Nitrogen at 24 h Outperform other Laboratory Markers in Predicting Persistent Organ Failure and Pancreatic Necrosis in Acute Pancreatitis: A Post Hoc Analysis of Three Large Prospective Databases

“…However, CRP levels are infl uenced by liver disease ( 11 ), which may be present in many patients with AP who are obese and/or alcoholics. Furthermore, CRP levels peak at 72-96 h aft er symptom onset, which can limit its prognostic accuracy as patients typically present at variable times aft er symptom onset ( 12,13 ). Finally, CRP is a laboratory marker that is not routinely measured in AP patients throughout the world.…”

Differential Effects of Caspase-1/Interleukin-1β–Converting Enzyme on Acinar Cell Necrosis and Apoptosis in Severe Acute Experimental Pancreatitis

“…Whereas the initiating events leading to the development of necrosis are still poorly understood, the subsequent infiltration of different leukocyte subsets into the damaged gland are claimed to be the major source for the release of various toxic mediators, such as proteolytic enzymes (Rinderknecht, 1994), oxygen free radicals (Poch et al, 1999;Rinderknecht, 1994), and cytokines (Fink and Norman, 1996). In this setting, potent proinflammatory cytokines, such as tumor necrosis factor-␣ (TNF-␣) and interleukin-1␤ (IL-1␤), have been shown to mediate enhanced local tissue destruction (Denham et al, 1997) and distant organ complications (Mayer et al, 2000;Norman et al, 1997a;Norman, 1998;Ogawa, 1998).…”

History and Evolution of the Management of Acute Pancreatitis

“…Cathepsin-B, a lysosomal cystein protease in the acinar cells, has been studied, and it has been shown to stimulate the conversion of trypsinogen to trypsin directly. Moreover, its complete inhibition blocks 90% of the conversion of trypsinogen to trypsin (1,2,30,31). Cathepsin-B also strongly activates mesotrypsinogen, one of the pancreatic isoforms of trypsinogen.…”

“…As reviewed previously, the pathophysiologic events in acute pancreatitis are initiated and perpetuated by failure of the control of the state of activation of the pancreatic enzymes in the acinar cell and ductal lumen. Some studies have demonstrated that gastric or duodenal feeding increases the production of enzymes by the pancreas, which may further stimulate or aggravate the disease process and cause more complications (1,2,30,31,74).…”