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Gut. 1998 Sep;43(3):408-13.

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

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1
Department and Laboratory of Experimental Gastroenterology, Erasme Hospital, Université Libre de Bruxelles, Belgium.

Abstract

BACKGROUND:

Interleukin 10 (IL-10) decreases the severity of experimental acute pancreatitis. The role of endogenous IL-10 in modulating the course of pancreatitis is currently unknown.

AIMS:

To examine the systemic release of IL-10 and its messenger RNA production in the pancrease, liver, and lungs and analyse the effects of IL-10 neutralisation in caerulein induced acute pancreatitis in mice.

METHODS:

Acute necrotising pancreatitis was induced by intraperitoneal caerulein. Serum levels of IL-10 and tumour necrosis factor (TNF), and tissue IL-10 and TNF-alpha gene expression were assessed. After injecting control antibody or after blocking the activity of endogenous IL-10 by a specific monoclonal antibody, the severity of acute pancreatitis was assessed in terms of serum enzyme release, histological changes, and systemic and tissue TNF production.

RESULTS:

In control conditions, serum IL-10 levels increased and correlated with the course of pancreatitis, with a maximal value eight hours after induction. Both IL-10 and TNF-alpha messengers showed a similar course, and were identified in the pancreas, liver, and lungs. Neutralisation of endogenous IL-10 significantly increased the severity of pancreatitis and 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-lethal model, systemic release of IL-10 correlates with the course of acute pancreatitis. This anti-inflammatory response parallels the release of TNF and both cytokines are produced multisystemically. Endogenous IL-10 controls TNF-alpha production and plays a protective role in the local and systemic consequences of the disease.

PMID:
9863488
PMCID:
PMC1727255
[Indexed for MEDLINE]
Free PMC Article
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