Induction of acute pancreatitis in germ-free rats: Evidence of a primary role for tumor necrosis factor-alpha

Background.: Tumor necrosis factor-α (TNF-α) has been implicated as a mediator of the systemic manifestations associated with acute pancreatitis. The purpose of this study was to show that TNF-α expression in pancreatitis is a primary response and is not the result of endotoxemia. Methods.: Severe acute pancreatitis was induced in germ-free rats, which have no source of endogenous endotoxin, by ductal infusion of artificial bile. Control animals underwent sham operation and ductal infusion of saline solution. TNF-α levels were measured by the WEHI bioassay. Endotoxin was measured by the Limulus assay. Results.: TNF-α levels remained low in the sham group (mean, 24.6±8.0 pg/ml) but were significantly elevated in normal rats with pancreatitis (181±26.8 pg/ml; p<0.001 versus sham group) and in germ-free rats with pancreatitis (213±90 pg/ml; p<0.002 versus sham group). No endotoxin was detected in any of the experimental rats. Conclusions.: Our results indicate that TNF-α levels are elevated in acute pancreatitis despite the absence of endotoxin, indicating a primary role of TNF-α in this disease.