Induction of acute pancreatitis in germ-free rats: evidence of a primary role for tumor necrosis factor-alpha.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha) has been implicated as a mediator of the systemic manifestations associated with acute pancreatitis. The purpose of this study was to show that TNF-alpha 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-alpha levels were measured by the WEHI bioassay. Endotoxin was measured by the Limulus assay.


RESULTS
TNF-alpha 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-alpha levels are elevated in acute pancreatitis despite the absence of endotoxin, indicating a primary role of TNF-alpha in this disease.
Hughes
C B
CB
Department of Surgery, University of Tennessee, Memphis 38163.
Gaber
L W
LW
Kotb
M
M
Mohey el-Din
A B
AB
Pabst
M
M
Gaber
A O
AO
D000208:Acute Disease; D000818:Animals; D001646:Bile; D004731:Endotoxins / Q000032:analysis; D005856:Germ-Free Life; D008033:Limulus Test; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid; D014357:Trypsin; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D013656:Taurocholic Acid; D014357:Trypsin