Effects of thalidomide in a mouse model of cerulein-induced acute pancreatitis

Current knowledge shows that pathophysiology of acute pancreatitis is characterized by intraacinar enzyme activation and subsequent dysregulation in immune response. Interactions between leukocytes, soluble mediators such as cytokines and vascular endothelium contribute to the systemic progression of the inflammatory response, whose entity may--in the end--determine disease severity and outcome. Recently, it has been shown that TNF-[alpha] may be a novel target for the treatment of acute pancreatitis; but the role of thalidomide, an immunomodulatory agent that inhibits TNF-(alpha) and angiogenesis, has not been investigated so far. The aim of the present study was to assess the effects of thalidomide in a murine model of necrotizing acute pancreatitis. Necrotizing acute pancreatitis was induced in mice by intraperitoneal injection of cerulein (hourly, x5, 50 microg/kg); in another group of animals, thalidomide was administered (200 mg/kg orally) at 1 h after first cerulein injection. After 24 h, biochemical, histological, and immunohistochemical evidences of acute pancreatitis developed in all cerulein-treated mice. On the contrary, pancreatitis histological features, amylase, lipase, TNF-alpha and IL-1beta levels, pancreas edema, and myeloperoxidase activity as well as immunohistochemical staining for inflammatory cytokines, leukocyte adhesion molecules, transforming growth factor [beta], vascular endothelial growth factor, and apoptosis-related proteins were found reduced in thalidomide-treated mice. Therefore, thalidomide treatment attenuates the development of acute pancreatitis caused by cerulein in mice. We propose that this evidence may help to clarify the role of anti-TNF-alpha and immunomodulatory agents in patients with acute pancreatitis.