Differential preservation of lipopolysaccharide-induced chemokine/cytokine expression during experimental pancreatitis-associated organ failure in rats shows a regulatory expressed phenotype.

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 microg/kg Escherichia coli 0111:B4 LPS was administered intra-arterially, 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 multiplex ELISA.
RESULTS: Four patterns were observed: (1) TNF-alpha, IL-1alpha, IL-1beta, IL-6, IFN-gamma, MCP-1, MIP-2alpha, MIP-3alpha, 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-2alpha and GRO/KC showed little or no difference between AP and controls, and (4) IL-10 concentrations after 0 and 6 microg/kg, but not 30 microg/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 2008 S. Karger AG, Basel.