Depletion of Neutrophils Protects Against L-Arginine-Induced Acute Pancreatitis in Mice

Abstract

Background/Aims: Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell damage and inflammation of the pancreas with infiltration of leukocytes, predominantly neutrophils. We investigated whether neutrophil depletion protects against experimental AP induced by L-arginine. Methods: AP was induced in C57BL/6 mice via two intraperitoneal L-arginine (4 g/kg) injections. Mice were pretreated with 250 and 100 µg anti-Gr-1 antibody via intraperitoneal injection at 24 and 4 h, respectively, before L-arginine challenge for neutrophil depletion. At 48 and 72 h after injection, the severity of AP was determined with the aid of biochemical and histological analyses. Amylase and MPO activity was detected using specific assay kits. The plasma cytokines levels were detected using ELISA. Results: Neutrophil depletion resulted in significantly reduced plasma amylase levels in pancreas, myeloperoxidase (MPO) activity in pancreas and lung, reactive oxygen species (ROS) generation and cell apoptosis, and decreased circulating neutrophil, tissue damage as well as expression levels of nuclear factor NF-κB. Conclusion: Neutrophil depletion is capable of reducing tissue damage of pancreas and lung in mice with acute pancreatitis.

Keywords

• Acute pancreatitis
• Neutrophils
• NF-κB