PMID- 21962809
OWN - NLM
STAT- MEDLINE
DCOM- 20120911
LR  - 20120611
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 176
IP  - 1
DP  - 2012 Jul
TI  - Suppressive effects of interleukin-18 on liver function in rat liver allografts.
PG  - 293-300
LID - 10.1016/j.jss.2011.07.053 [doi]
AB  - BACKGROUND: Interleukin-18 (IL-18) is a potent proinflammatory cytokine that 
      augments both innate and acquired immune responses. It is also a crucial 
      regulator of lymphocyte production of interferon-gamma (IFN-gamma), which can promote 
      acute cellular rejection of transplanted solid organs. METHODS: To evaluate the 
      role of IL-18 in liver transplantation, we constructed an adenoviral vector 
      encoding IL-18 binding protein (Adex-IL18bp), which specifically suppressed the 
      biologic activity of IL-18, and examined the effect of this suppression on liver 
      allografts by using a high-responder rat model (ACI to Lewis) of orthotopic liver 
      transplantation (OLTx). Donor rats were given one intravenous injection of 
      Adex-IL18bp or Adex-LacZ (control vector) 2 d before OLTx. RESULTS: Seven days 
      after OLTx, overexpression of IL-18bp resulting from the adenovirus gene transfer 
      was associated with significantly decreased serum alanine aminotransferase levels 
      and less histologic hepatic injury in recipient rats with Adex-IL18bp-pretreated 
      donors compared with Adex-LacZ controls. Adex-IL18bp pretreatment also 
      significantly prolonged rat/allograft survival, inhibited expression of IFN-gamma, 
      and reduced levels (versus control values) of both CXCL10 and CX3CL1, which can 
      be induced by IFN-gamma. CONCLUSION: These results suggest that IL-18 has an 
      important role in liver allograft rejection through IFN-gamma and chemokines and that 
      specific suppression of IL-18 may improve liver function early after 
      transplantation.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Ono, Shigeshi
AU  - Ono S
AD  - Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
FAU - Obara, Hideaki
AU  - Obara H
FAU - Takayanagi, Atsushi
AU  - Takayanagi A
FAU - Tanabe, Minoru
AU  - Tanabe M
FAU - Kawachi, Shigeyuki
AU  - Kawachi S
FAU - Itano, Osamu
AU  - Itano O
FAU - Shinoda, Masahiro
AU  - Shinoda M
FAU - Kitago, Minoru
AU  - Kitago M
FAU - Hibi, Taizo
AU  - Hibi T
FAU - Chiba, Tomohiro
AU  - Chiba T
FAU - Du, Wenlin
AU  - Du W
FAU - Matsumoto, Kenji
AU  - Matsumoto K
FAU - Tilles, Arno W
AU  - Tilles AW
FAU - Yarmush, Martin L
AU  - Yarmush ML
FAU - Aiso, Sadakazu
AU  - Aiso S
FAU - Shimizu, Nobuyoshi
AU  - Shimizu N
FAU - Sakamoto, Michiie
AU  - Sakamoto M
FAU - Kitagawa, Yuko
AU  - Kitagawa Y
LA  - eng
PT  - Journal Article
DEP - 20110827
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Chemokines)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (interleukin-18 binding protein)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Chemokines/metabolism
MH  - Graft Survival/drug effects/*physiology
MH  - Intercellular Signaling Peptides and Proteins/genetics/pharmacology
MH  - Interferon-gamma/metabolism
MH  - Interleukin-18/antagonists & inhibitors/*physiology
MH  - Liver/drug effects/*metabolism
MH  - Liver Transplantation/*physiology
MH  - Male
MH  - Models, Animal
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Transplantation, Homologous
EDAT- 2011/10/04 06:00
MHDA- 2012/09/12 06:00
CRDT- 2011/10/04 06:00
PHST- 2011/05/04 00:00 [received]
PHST- 2011/07/19 00:00 [revised]
PHST- 2011/07/25 00:00 [accepted]
PHST- 2011/10/04 06:00 [entrez]
PHST- 2011/10/04 06:00 [pubmed]
PHST- 2012/09/12 06:00 [medline]
AID - S0022-4804(11)00683-4 [pii]
AID - 10.1016/j.jss.2011.07.053 [doi]
PST - ppublish
SO  - J Surg Res. 2012 Jul;176(1):293-300. doi: 10.1016/j.jss.2011.07.053. Epub 2011 
      Aug 27.