The Role Of Macrophage Migration Inhibitory Factor In Rats' Acute Pancreatitis And Effects Of Treatment With Sandostatin

OBJECTIVE: This study investigated the role of MIF in the pathogenesis of acute pancreatits(AP) and the relationship with inflammatory cytokines (Tumor necrosis factor-α, TNF-α) and anti-inflammatory cytokines (Interleukin 10, IL-10). The curative effect of somatostatin analogues (Sandostatin) was observed in experimental acute pancreatitis.METHODS:Seventy Sprague-Dawley male rats were randomly divided into three groups. They included control group (n=10), acute necrotizing pancreatitis group (ANP group, n=30) and treatment group (n=30). The ANP group received two intraperitoneal injections of 10% L-arginine (2.0mg/g) at intervals. The treatment group was treated with sandostatin(10μg/kg, hypodermic injection) at the 0nd, 12th, 24th, and 36th hour after the last injection of L-arginine. The control group received intraperitoneal injection of normal sodium alone. Blood samples were collected from the abdominal aorta at the 0th, 6th, 12th, 24th and 48th hour after the last L-arginine injection. The serum MIF, TNF-αand IL-10 levels were determined by enzyme linked immunosorbent assay (ELISA). Serum amylase levels in blood samples were measured and histopathological score were recorded in three groups.RESULTS: (1) Serum amylase levels and pancreatic histopathological scores were higher in ANP rats than control rats significantly (p<0.05). (2)Compared with those of the control group, serum MIF and TNF-αlevels in ANP rats increased (p<0.05). Levels of IL-10 didn't increase obviously in the beginning, but worked up after 24th and the highest at 48th. (3)Serum MIF levels in the ANP group showed the direct relationship with TNF-α(r=0.95,p=0.01), but no the correlation with IL-10(r=0.77,p=0.13). (4)Serum amylase levels, MIF, TNF-α, IL-10 and pancreatic histopathological scores were lower in treatment group than the ANP group significantly (p<0.05).CONCLUSION: (1) MIF expression increased significantly in acute pancreatitis. This suggest that MIF may be the pathogenesis of acute pancreatitis. (2)MIF may be an early cytokine of the inflammatory cascade in the pathogenesis of acute pancreatitis, and the biological effect is correlated with the expression of TNF-α. But MIF has no indefensible relationship with IL-10. (3)Both inflammatory and anti-inflammatory cytokines increased remarkably in the rats model of acute pancreatitis.This result indicates that there is a potential tendency of inflammatory response syndrome and compensatory anti-inflammatory response syndrome in the course of acute pancreatitis. (4) The curative effect of Sandostatin was positive in acute pancreatitis. The possible mechanisms may involve attenuation of immune reaction through inhibitting both inflammatory and anti-inflammatory cytokines expression in acute pancreatitis.