Background: Altered lipopolysaccharide (LPS)-responsiveness is a key feature of acute pancreatitis (AP)-associated multiple organ failure (AP-MOF) in rats and humans. Aim: To determine the differential expression of 16 cytokines and chemokines in response to delayed LPS administration in established experimental AP-MOF in rats. Methods: In a cubic factorial group design ( 12 groups, n = 6 rats/group), 0, 6 and 30 mu g/kg Escherichia coli 0111:B4 LPS was administered intraarterially, 18 h into experimental AP-MOF or sham laparotomy. AP was induced by intraductal glycodeoxycholic acid and intravenous caerulein. Central venous serum concentrations of 16 cytokines and chemokines were measured by Searchlight (TM) multiplex ELISA. Results: Four patterns were observed: (1) TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, IFN-gamma, MCP-1, MIP-2 alpha, MIP-3 alpha, fractalkine and RANTES showed a diminished LPS response in AP versus sham (p < 0.001, ANOVA); (2) IL-2, IL-4 and GM-CSF levels were undetectable; (3) CINC-2 alpha and GRO/KC showed little or no difference between AP and controls, and (4) IL-10 concentrations after 0 and 6 mu g/kg, but not 30 mu g/kg LPS injection were significantly higher in AP than controls (p < 0.001, ANOVA). Conclusion: Experimental AP-MOF in rats results in differential preservation of the cytokine and chemokine response to LPS challenge, with a predominantly regulatory expressed phenotype. Copyright (C) 2008 S. Karger AG, Basel and IAP.