Multisystemic production of interleukin 10 limits the severity of acute pancreatitis in mice

Background—Interleukin 10 (IL-10)decreases the severity of experimental acute pancreatitis. The role ofendogenous IL-10 in modulating the course of pancreatitis is currently unknown.
Aims—To examine the systemicrelease of IL-10 and its messenger RNA production in the pancreas,liver, and lungs and analyse the effects of IL-10 neutralisation incaerulein induced acute pancreatitis in mice.
Methods—Acute necrotisingpancreatitis was induced by intraperitoneal caerulein. Serum levels ofIL-10 and tumour necrosis factor (TNF), and tissue IL-10 and TNF-αgene expression were assessed. After injecting control antibody orafter blocking the activity of endogenous IL-10 by a specificmonoclonal antibody, the severity of acute pancreatitis was assessed interms of serum enzyme release, histological changes, and systemic andtissue TNF production.
Results—In control conditions,serum IL-10 levels increased and correlated with the course ofpancreatitis, with a maximal value eight hours after induction. BothIL-10 and TNF-α messengers showed a similar course, and wereidentified in the pancreas, liver, and lungs. Neutralisation ofendogenous IL-10 significantly increased the severity of pancreatitisand associated lung injury as well as serum TNF protein levels (+75%)and pancreatic, pulmonary, and hepatic TNF messenger expression (+33%,+29%, +43%, respectively).
Conclusions—In this non-lethalmodel, systemic release of IL-10 correlates with the course of acutepancreatitis. This anti-inflammatory response parallels the release ofTNF and both cytokines are produced multisystemically. Endogenous IL-10controls TNF-α production and plays a protective role in the localand systemic consequences of the disease.

Keywords:pancreatitis; interleukin 10; tumour necrosis factorα; adult respiratory distress syndrome