Anti-TNFalpha therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat.
BACKGROUND
Elevated levels of tumor necrosis factor-alpha (TNFalpha) have been measured in a lethal model acute pancreatitis (AP) and may contribute to the pathophysiologic sequelae of the disease.


METHODS
To determine the significance of anti-TNFalpha therapy on survival and disease manifestations in a clinically relevant model of AP, a rat model was developed using a retrograde pancreatic ductal infusion of bile. Animals were randomized to no treatment (n = 30) or treatment with anti-TNFalpha antibody 15 minutes prior to induction of AP (n = 30). Five treated and 5 untreated rats were killed at various time periods up to 72 hours to provide temporal characterization of TNFalpha activity in AP.


RESULTS
A burst Of TNFalpha activity in the serum of untreated pancreatitis animals between 1 and 3 hours after induction of the disease is prevented by pretreatment with anti-TNFalpha antibody.


CONCLUSIONS
These findings provide a plausible mechanism for the improvement in biochemical and histologic parameters as well as in overall survival in an experimental model of acute pancreatitis in the rat.
Hughes
C B
CB
Department of Surgery, University of Tennessee, College of Medicine, Memphis, USA.
Grewal
H P
HP
Gaber
L W
LW
Kotb
M
M
El-din
A B
AB
Mann
L
L
Gaber
A O
AO
D000208:Acute Disease; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D014409:Tumor Necrosis Factor-alpha