• Changbin Shi, Xia Zhao, Anna Lagergren, Mikael Sigvardsson, Xiangdong Wang, and Roland Andersson.
• Department of Surgery, Lund University Hospital, Lund, Sweden.
• Scand. J. Gastroenterol. 2006 Apr 1; 41 (4): 472-80.

ObjectiveAcute pancreatitis (AP) is an inflammatory disorder that develops a complex cascade of immunological events. The local and systemic immune status and inflammatory response might contribute to the understanding of underlying pathophysiological mechanisms and potential treatment.Material And MethodsSevere AP was induced by intraductal perfusion of 5% sodium taurodeoxycholate in rats. mRNA expression of cytokines and chemokines was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and NF-kappaB activation was assessed by electrophoretic mobility shift assay in fresh pancreatic acini and circulating monocytes 1, 3, 6 or 9 h after sham operation, induction of AP or N-acetylcysteine (NAC) pretreatment. Flow cytometry was performed on cells obtained from the peripheral blood.ResultsAn inverse relationship in pancreatic and circulating monocytic NF-kappaB activation was detected 6 and 9 h after induction of AP. NAC further suppressed monocytic NF-kappaB activation induced by AP as seen 9 h after induction of AP. A marked constitutive increase in the expression of IL-6, CINC and MCP-1 was seen in pancreatic acini, whereas no change in mRNA expression of inflammatory mediators was observed in circulating monocytes 6 h after induction of AP. Flow cytometry further confirmed the altered function of circulating monocytes.ConclusionsThe different immune status and inflammatory response in the pancreas and circulating monocytes improve the understanding of the mechanisms by which systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) develop in severe AP. A potential therapeutic approach could be to restore the functional capacity of the immune system in AP. The use of an NF-kappaB inhibitor, preferentially reaching the local inflammatory foci, could be a potential future way of intervention.

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