Recombinant human interleukin-11 decreases severity of acute necrotizing pancreatitis in mice.

Interleukin (IL)-11 has anti-inflammatory activity in animal models of gut inflammation, endotoxemia, and radiation-induced thoracic injury. The aim of the present study was to investigate the protective role of IL-11 in a model of acute necrotizing pancreatitis in mice. Acute pancreatitis was induced by administration of seven intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. Lipopolysaccharide (LPS) was injected 5 hours after the first cerulein injection. Treatment with recombinant human IL-11 (rhIL-11) was started 30 minutes before the first cerulein injection and repeated 4 hours later. Serum levels of amylase, lipase, and tumor necrosis factor (TNF)-alpha were measured at the end of the experiments. The severity of pancreatitis was evaluated by histological scoring using a semiquantitative analysis of hematoxylin and eosin-stained sections of the pancreas. Competitive reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the intrapancreatic TNF-alpha mRNA levels. Serum amylase and lipase levels progressively increased with a maximum reached between 8 and 11 hours. Treatment with rhIL-11 significantly decreased amylase and lipase levels at 6 and 8 hours. Serum TNF-alpha peaked at 6 hours and rapidly decreased thereafter. The elevation of serum TNF-alpha was markedly inhibited by treatment with rhIL-11. Histologically, treatment of rhIL-11 reduced the severity of pancreatic injury including edema, inflammatory cell infiltration, and hemorrhage at 6 hours. Intrapancreatic TNF-alpha mRNA levels were reduced by >50% in the rhIL-11-treated group at 6 hours. In conclusion, rhIL-11 decreased the severity of experimental pancreatitis early on but not later and inhibited the intrapancreatic TNF mRNA expression in vivo, suggesting that the protective effect of IL-11 during the early stage of acute pancreatitis may be mediated, at least in part, through modulation of TNF production.