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.


OBJECTIVE
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).


CONCLUSIONS
Experimental AP-MOF in rats results in differential preservation of the cytokine and chemokine response to LPS challenge, with a predominantly regulatory expressed phenotype.
Mole
Damian J
DJ
Clinical and Surgical Sciences (Surgery), University of Edinburgh, Edinburgh, UK. damian.mole@ed.ac.uk
McFerran
Neil V
NV
Diamond
Thomas
T