Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders

Abstract

Macrophage migration inhibitory factor (MIF) is a unique protein, participating in inflammation, immune response, and cell growth. MIF was first discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including phagocytosis, spreading, and tumoricidal activity. It has been reported that MIF is associated with the pathogenesis of a variety of diseases. MIF expression was increased at inflammatory sites in diseases such as rheumatoid arthritis and glomerulonephritis. In experimental inflammatory disease, blockade of MIF bioactivity inhibited the severity of disease activity. On the other hand, MIF expression is also increased in tumor lesions, and MIF plays a role as a cell growth factor. MIF has been reported to be constitutively expressed in gut, liver, and pancreas. In patients with gastritis, inflammatory bowel disease, hepatitis, and pancreatitis, MIF expression was remarkably increased in both the serum and the local lesions. Blockade of MIF bioactivity inhibited and prevented inflammation in experimental gastritis, colitis, hepatitis, and pancreatitis. On the other hand, MIF expression was higher than that in normal tissues in colonic carcinomas and hepatocellular carcinoma both in vivo and in vitro. Blockade of MIF bioactivity successfully inhibited tumor cell growth in vivo and in vitro. MIF plays important roles in the pathogenesis of gastrointestinal, hepatic, and pancreatic disorders.