title: Multisystemic production of interleukin 10 limits the severity of acute pancreatitis in mice.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department and Laboratory of Experimental Gastroenterology, Erasme Hospital, Université Libre de Bruxelles, Belgium.
authors.forename: J L
authors.initials: JL
authors.lastname: Van Laethem
authors.forename: R
authors.initials: R
authors.lastname: Eskinazi
authors.forename: H
authors.initials: H
authors.lastname: Louis
authors.forename: F
authors.initials: F
authors.lastname: Rickaert
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
authors.forename: J
authors.initials: J
authors.lastname: Devière
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002108:Ceruletide; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008049:Lipase / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism*; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002108:Ceruletide; D008049:Lipase; D000681:Amylases