Active interleukin-1 receptor required for maximal progression of acute pancreatitis.

Abstract:

OBJECTIVE:The authors' aim was to determine the requirement for an active interleukin (IL)-1 receptor during the development and progression of acute pancreatitis. SUMMARY OF BACKGROUND DATA:Interleukin-1 is a pro- inflammatory cytokine that has been shown to be produced during acute pancreatitis. Earlier animal studies of moderate and severe pancreatitis have shown that blockade of this powerful mediator is associated with attenuated pancreatic destruction and dramatic increases in survival. The exact role played by IL-1 and the requirement for activation of its receptor in the initiation and progression of pancreatitis is unknown. METHODS:Conventional and IL-1 receptor "knockout" animals were used in parallel experiments of acute pancreatitis induced by intraperitoneal injection of cerulean (50 microg/kg every 1 hour X 4). The conventional mouse strain had the IL-1 receptor blocked prophylactically by means of a recombinant IL-1 receptor antagonist (10 mg/kg injected intraperitoneally every 2 hours). The second mouse strain was genetically engineered by means of gene targeting in murine embryonic stem cells to be devoid of type 1 IL-1 receptor (IL-1 receptor knockout). Animals were killed at 0, 0.5, 1, 2, 4, and 8 hours, with the severity of pancreatitis determined by serum amylase, lipase, and IL-6 levels and blind histologic grading. Strain-specific controls were used for comparison. RESULTS:The genetic absence of the IL-1 receptor or its pharmacologic blockade resulted in significantly attenuated pancreatic vacuolization, edema, necrosis, inflammation, and enzyme release. Serum IL-6, a marker of inflammation severity, was dramatically decreased in both groups. CONCLUSIONS:Activation of the IL-1 receptor is not required for the development of pancreatitis but apparently is necessary for the maximal propagation of pancreatic injury and its associated inflammation.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

Norman JG,Fink G,Franz M,Guffey J,Carter G,Davison B,Sexton C,Glaccum M

doi

10.1097/00000658-199602000-00008

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

163-9

issue

2

eissn

0003-4932

issn

1528-1140

journal_volume

223

pub_type

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