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 beta, IL-6 and IL-8, the anti-inflammatory cytokine IL-10, interleukin 1 beta 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 beta/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 beta-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.

Figure 1

Time course of the proinflammatory mediators (interleukins (IL)-1β, IL-6, and IL-8, and soluble interleukin 2 receptor (sIL-2R)) in serum in human acute pancreatitis. Values are median (interquartile range). SAP, severe acute pancreatitis; MAP, mild acute pancreatitis.

Figure 2

Time course of the anti-inflammatory mediators (interleukin 10 (IL-10) and interleukin 1β receptor antagonist (IL-1RA)) in serum in human acute pancreatitis. Values are median (interquartile range). SAP, severe acute pancreatitis; MAP, mild acute pancreatitis.