Interleukin-22 therapy attenuates the development of acute pancreatitis in rats

Abstract

Human acute pancreatitis (AP) is a potential serious disease with a limited specific therapy. Here, we assessed the therapeutic efficacy of interleukin-22 (IL-22), a newly emerged cytokine with unique biological activities, in the treatment of a rat model of severe AP. For induction of AP, rats were intraperitoneally (i.p.) injected with nine doses of caerulein (50 μg/kg/dose) at 1-h intervals. Recombinant rat IL-22 (rIL-22) was given in three doses (4 μg/rat/dose; i.p.) after the 1st, 5th, and 9th caerulein injection. Serum levels of pancreatic α-amylase and lipase, pancreatic weight/body weight ratio, histological score of pancreatic injury, intrapancreatic expression of myeloperoxidase (MPO; as an index of neutrophils infiltration) and cyclooxygenase-2 (COX-2), and the serum and pancreatic levels of pro-inflammatory prostaglandin E2 (PGE2); monocyte chemotactic protein-1 (MCP-1); and Interleukin-1β (IL-1β) were collectively analyzed as diagnostic parameters of the induced AP. Results showed that administration of rIL-22 significantly repressed caerulein-evoked substantial hyperamylasemia and hyperlipasemia, severe pancreatic injury and edema. Also the administered rIL-22 significantly reduced caerulein-induced intrapancreatic overexpression of COX-2 and MPO, and the production of proinflammatory mediators (PGE2, MCP-1 and IL-1β) in the systemic circulation and pancreatic tissues. Taken together, these results indicate the potential therapeutic efficacy of IL-22 against AP by acting as an anti-inflammatory agent. Key words: Interleukin-22, acute pancreatitis, myeloperoxidase, cyclooxygenase-2, prostaglandin E2, monocyte chemotactic protein-1, interleukin-1β.