CC-chemokine activation in acute pancreatitis:: enhanced release of monocyte chemoattractant protein-1 in patients with local and systemic complications

Objective: Systemic leukocyte activation is claimed to trigger inflammatory response and remote organ dysfunction in acute pancreatitis. Chemokines are inflammatory mediators with potent leukocyte-activating properties and have been shown to be involved in the pathophysiological process of experimental acute pancreatitis. However, as little is known about their role in human disease we investigated local and systemic concentrations of different CC-chemokine members in patients with acute pancreatitis. Patients and methods: We included 68 patients with acute pancreatitis in the present study. Local complications in terms of necrosis were present in 37 (54%) patients of whom 21 (57%) developed pancreatic infections.. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta) concentrations were measured daily over 2 weeks after study inclusion by ELISA in sera and lesser sac aspirates. Results: MCP-1 serum concentrations showed a dramatic increase in patients who developed local complications and/or remote organ failure. Herein, a close correlation was found between the severity of remote organ failure and the degree of MCP-1 elevation. Multiple regression analysis identified pancreatic infections as well as renal and cardiocirculatory failure as independent variables associated with enhanced systemic MCP-1 release. MIP-1alpha levels remained unaffected by local complications and showed a significant increase only; if multiple organ dysfunction syndrome (MODS) developed or patients subsequently died. In contrast, MIP-1beta concentrations correlated with neither the presence nor the severity of any complication. Compared with systemic concentrations, local lesser sac aspirates revealed significantly higher levels of MCP-1, whereas MIP-1alpha and MIP-1beta were not different. Conclusions: Complicated acute pancreatitis is associated with significantly elevated local and systemic concentrations of the CC-chemokine MCP-1. Our results suggest that, among the CC-chemokine members investigated, MCP-1 might play a pivotal role in the pathological mechanism of complicated acute pancreatitis.