Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis

Background & Aims: Macrophage migration inhibitory factor (MIF), originally described as an inhibitor of the random migration of macrophages, has been shown recently to be involved in the pathogenesis of several inflammatory diseases such as sepsis. The aim of this study was to clarify the role of MIF in acute pancreatitis (AP). Methods: Hemorrhagic necrotizing pancreatitis and edematous pancreatitis were induced by the injection of taurocholic acid (TCA pancreatitis) and cerulein (cerulein pancreatitis), respectively, on male Wistar rats. MIF levels in ascitic fluids, serum, and the organs were determined. The effects of anti-MIF antibody were examined on the prognosis of rats with TCA pancreatitis and of female CD-1 mice with choline-deficient, ethionine-supplemented, diet-induced model of severe AP. In addition, serum MIF levels in AP patients and in healthy controls were measured. Results: Serum and ascitic MIF levels in TCA pancreatitis were increased rapidly and decreased gradually thereafter. Ascitic MIF levels were also increased in cerulein pancreatitis, but to a lesser degree. MIF level was increased in the lung in TCA pancreatitis, but not in the pancreas and the liver. Prophylactic (1 hour before and immediately after induction) administration of anti-MIF antibody significantly improved the survival rate of rats with TCA pancreatitis. The survival rate of mice with severe AP was also improved significantly by the antibody treatment. Serum MIF levels were higher in severe AP patients than mild AP patients and healthy controls. Conclusions: These results suggest a role of MIF in the pathogenesis of severe AP.