Inhibition of TNF alpha improves survival in an experimental model of acute pancreatitis.
The development of systemic complications in acute pancreatitis is largely responsible for the mortality associated with this disease. The systemic sequelae encountered in acute pancreatitis are similar to those occurring in patients with septic shock, a syndrome of multiple organ failure thought to be related to overproduction of inflammatory cytokines. As with sepsis, data is mounting that cytokines, particularly TNF alpha, may play a central role in acute pancreatitis and mediate the systemic sequelae of the disease. We have previously shown elevated levels of TNF alpha in the serum of animals with experimental acute pancreatitis. In this study, we use a bile-infusion model of pancreatitis in the rat to show amelioration of disease severity as well as a distinct survival advantage by TNF alpha blockade using anti-TNF alpha polyclonal antibody. These data provide strong evidence that TNF alpha is a major contributor to the morbidity and mortality from acute pancreatitis.
Hughes
C B
CB
Department of Surgery, University of Tennessee, College of Medicine, Memphis 38163, USA.
Gaber
L W
LW
Mohey el-Din
A B
AB
Grewal
H P
HP
Kotb
M
M
Mann
L
L
Gaber
A O
AO
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001201:Ascites / Q000473:pathology; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D006400:Hematocrit; D006470:Hemorrhage / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D010195:Pancreatitis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha