The role of tumor necrosis factor-alpha in the aggravation of cerulein-induced pancreatitis in rats

Abstract

Severe acute pancreatitis is often complicated by intraperitoneal infection, resulting in multiple organ failure (MOF). It is known to elevate serum tumor necrosis factor (TNF-alpha) in patients with sepsis and/or MOF. In order to study the role of TNF-alpha in the aggravation of acute pancreatitis, we investigated TNF-alpha production by peritoneal macrophages in acute pancreatitis rat using the cerulein-induced pancreatitis model. TNF-alpha production by isolated peritoneal macrophages following lipopolysaccharide (LPS) stimulation was significantly increased in pancreatitis rats as compared with nonpancreatitis control rats (p < 0.001). Serum TNF-alpha activity was elevated following intraperitoneal administration of LPS as the septic challenge both in pancreatitis rats and in control rats, being significantly higher in the former (p < 0.05). Histological findings and liver function tests revealed that LPS induced more severe liver damage in pancreatitis rats than in control rats within 24 h after LPS administration. These results indicate that increased TNF-alpha production by peritoneal macrophages in acute pancreatitis augmented LPS-induced liver injury and suggest the possibility that TNF-alpha may play a role in the development of MOF during acute pancreatitis complicated by intraabdominal sepsis.