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.