PMID- 16317388
OWN - NLM
STAT- MEDLINE
DCOM- 20060317
LR  - 20220318
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 24
IP  - 6
DP  - 2005 Dec
TI  - Role of interleukin 18 in nitric oxide production and pancreatic damage during 
      acute pancreatitis.
PG  - 564-70
AB  - 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.
FAU - Ueno, Naoko
AU  - Ueno N
AD  - Department of Emergency and Disaster Medicine, Institute for Advanced Medical 
      Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
FAU - Kashiwamura, Shin-Ichiro
AU  - Kashiwamura S
FAU - Ueda, Haruyasu
AU  - Ueda H
FAU - Okamura, Haruki
AU  - Okamura H
FAU - Tsuji, Noriko M
AU  - Tsuji NM
FAU - Hosohara, Katsushi
AU  - Hosohara K
FAU - Kotani, Joji
AU  - Kotani J
FAU - Marukawa, Seishiro
AU  - Marukawa S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Interleukin-18)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Female
MH  - *Gene Expression Regulation, Enzymologic/drug effects
MH  - Interleukin-18/administration & dosage/deficiency/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase Type II/*biosynthesis
MH  - Pancreas/*enzymology/pathology
MH  - Pancreatitis/chemically induced/drug therapy/*metabolism/pathology
EDAT- 2005/12/01 09:00
MHDA- 2006/03/18 09:00
CRDT- 2005/12/01 09:00
PHST- 2005/12/01 09:00 [pubmed]
PHST- 2006/03/18 09:00 [medline]
PHST- 2005/12/01 09:00 [entrez]
AID - 00024382-200512000-00012 [pii]
AID - 10.1097/01.shk.0000184285.57375.bc [doi]
PST - ppublish
SO  - Shock. 2005 Dec;24(6):564-70. doi: 10.1097/01.shk.0000184285.57375.bc.