THE ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA IN THE AGGRAVATION OF CERULEIN-INDUCED PANCREATITIS IN RATS

Severe acute pancreatitis is often complicated by intraperitoneal infe ction, resulting in multiple organ failure (MOF). It is known to eleva te 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 peritonea l macrophages in acute pancreatitis rat using the cerulein-induced pan creatitis model. TNF-alpha production by isolated peritoneal macrophag es following lipopolysaccharide (LPS) stimulation was significantly in creased in pancreatitis rats as compared with nonpancreatitis control rats (p < 0.001). Serum TNF-alpha activity was elevated following intr aperitoneal administration of LPS as the septic challenge both in panc reatitis rats and in control rats, being significantly higher in the f ormer (p < 0.05). Histological findings and liver function tests revea led that LPS induced more severe liver damage in pancreatitis rats tha n 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 M OF during acute pancreatitis complicated by intraabdominal sepsis.