Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis.
OBJECTIVE
Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection.


METHODS
An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-alpha were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied.


RESULTS
In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-alpha level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate.


CONCLUSIONS
The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy.
Matheus
Andre S
AS
Gastroenterology Department, University of Sao Paulo, Sao Paolo, Brazil. asmatheus@hotmail.com
Coelho
Ana Maria M
AM
Sampietre
Sandra
S
Patzina
Rosely
R
Jukemura
Jose
J
Cunha
Jose Eduardo M
JE
Machado
Marcel C C
MC