Therpay with recombinant interleukin-22 attenuates the development of acute pancreatitis in rats

ABSTRACT

Acute pancreatitis [AP], especially its sever form, is a potential serious human 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 induced by caerulein. For disease induction, the animals were intraperitoneally [i.p.] injected with nine doses of caerulein [50 micro g/kg/dose] at 1-h intervals. Recombinant rat IL-22 [rIL-22] was given [4 micro g/rat/dose; i.p.] after the 1[st], 5[th], and 9[th] caerulein injection. Twelve hours after the last caerulein injection, the animals were euthanized under anesthesia and their bloodd specimens and pancreases were collected and examined. Serum levels of pancreatic alpha-amylase and lipase, pancreatic weight/body weight ratio, histopathological feature of induced pancreatic injury, intrapancreatic expression of cyclooxygenase-2 [COX-2] and myeloperoxidase [MPO; an index of neutrophils infiltration], and concentrations of pro-inflammatory prostaglandin E2 [PGE2]; monocyte chemotactic protein-1 [MCP-1]; and interleukin-1 beta [IL-1beta] in the serum and pancreatic tissues were collectively analyzed as diagnostic parameters of the induced AP. Results showed that therapy with rIL-22 significantly repressed caerulein-induced severe injury and edema in the pancreatic tissues. Administration of rIL-22 significantly reduced caerulein-evoked substantial hyperamylasemia and hyperlipasemia, intrapancreatic over-expression of COX-2 and MPO, and the production of proinflammatory mediators [PGE2, MCP-1 and IL-1beta] in the pancreatic tissues and systemic circulation. These biochemical observations were also supported by the histopathological findings. In conclusion, these results indicate the favorable attenuating effect of IL-22 against the development of AP by acting as an anti-inflammatory agent