TY - JOUR
T1 - Anti-TNFα therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat
AU - Hughes, Christopher B.
AU - Grewal, Hani P.
AU - Gaber, Lillian W.
AU - Kotb, Malak
AU - El-Din, Abou Bakr Mohey
AU - Mann, Linda
AU - Gaber, A. Osama
PY - 1996/2
Y1 - 1996/2
N2 - BACKGROUND: Elevated levels of tumor necrosis factor-alpha (TNFα) have been measured in a lethal model of acute pancreatitis (AP) and may contribute to the pathophysiologic sequelae of the disease. METHODS: To determine the significance of anti-TNFα 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-TNFα 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 TNFα activity in AP. RESULTS: A burst of TNFα activity in the serum of untreated pancreatitis animals between 1 and 3 hours after induction of the disease is prevented by pretreatment with anti-TNFα 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.
AB - BACKGROUND: Elevated levels of tumor necrosis factor-alpha (TNFα) have been measured in a lethal model of acute pancreatitis (AP) and may contribute to the pathophysiologic sequelae of the disease. METHODS: To determine the significance of anti-TNFα 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-TNFα 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 TNFα activity in AP. RESULTS: A burst of TNFα activity in the serum of untreated pancreatitis animals between 1 and 3 hours after induction of the disease is prevented by pretreatment with anti-TNFα 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.
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U2 - 10.1016/S0002-9610(97)89568-2
DO - 10.1016/S0002-9610(97)89568-2
M3 - Article
C2 - 8619467
AN - SCOPUS:0029664603
SN - 0002-9610
VL - 171
SP - 274
EP - 280
JO - American Journal of Surgery
JF - American Journal of Surgery
IS - 2
ER -