Document Detail

Role of interleukin 18 in nitric oxide production and pancreatic damage during acute pancreatitis.
MedLine Citation:
PMID:  16317388     Owner:  NLM     Status:  MEDLINE    
The release of the immunomodulator, interleukin 18 (IL-18) into sera early in acute pancreatitis (AP) corresponds to disease severity. IL-18 induces nitric oxide (NO), which is involved in the pathophysiology of pancreatitis. The objective of this study was to clarify the role of IL-18 in pathogenesis and NO production during early AP using recombinant mouse (rm) IL-18 protein and IL-18 gene knockout (KO) mice. After pretreatment with phosphate-buffered saline or rmIL-18, wild-type (WT) or KO mice were injected intraperitoneally with phosphate-buffered saline (sham) or cerulein (AP) hourly for 3 h. Blood, pancreas, spleen, and liver were collected until 24 h after the first dose. Main outcome measures were serum IL-18, amylase and lipase levels, histological evaluation of the pancreas with parenchyma vacuolization of acinar cells, mRNA expression of inducible NO synthase (iNOS) in the pancreas, and spleen, liver, and plasma NO metabolite level. Serum IL-18 was significantly increased immediately after induction of AP in WT mice. Serum amylase, lipase, and the numbers of acinar cells with parenchyma vacuolization were significantly higher in the group AP/KO than in the group AP/WT, but these parameters were improved by dose-dependent pretreatment with rmIL-18 administration in both groups. Pancreatic iNOS gene expression and plasma NO metabolites were significantly increased by 6 h after the initiation of AP, but were significantly lower in the group AP/KO than in the AP/WT mice. Pretreatment with rmIL-18 also significantly increased these levels in both groups. Splenic and hepatic iNOS expression was not changed after the initiation of AP in WT mice, whereas pretreatment with rmIL-18 also increased these levels. Administration of aminoguanidine, a selective iNOS inhibitor, before AP induction abolished the protective effect of pretreatment with rmIL-18 on pancreatic injury. IL-18 appears to protect the pancreas during early induced-induced AP in mice, probably through induction of NO release from an iNOS source. IL-18 may be a target for new AP therapeutics.
Naoko Ueno; Shin-Ichiro Kashiwamura; Haruyasu Ueda; Haruki Okamura; Noriko M Tsuji; Katsushi Hosohara; Joji Kotani; Seishiro Marukawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  24     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-30     Completed Date:  2006-03-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  564-70     Citation Subset:  IM    
Department of Emergency and Disaster Medicine, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
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MeSH Terms
Acute Disease
Gene Expression Regulation, Enzymologic* / drug effects
Interleukin-18 / administration & dosage,  deficiency,  metabolism*
Mice, Inbred BALB C
Mice, Knockout
Nitric Oxide / biosynthesis*
Nitric Oxide Synthase Type II / biosynthesis*
Pancreas / enzymology*,  pathology
Pancreatitis / chemically induced,  drug therapy,  metabolism*,  pathology
Reg. No./Substance:
0/Interleukin-18; 10102-43-9/Nitric Oxide; EC Oxide Synthase Type II

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