title: Suppressive effects of interleukin-18 on liver function in rat liver allografts.
abstract: 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-γ (IFN-γ), 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-γ, and reduced levels (versus control values) of both CXCL10 and CX3CL1, which can be induced by IFN-γ.
  
  
  CONCLUSIONS
  These results suggest that IL-18 has an important role in liver allograft rejection through IFN-γ and chemokines and that specific suppression of IL-18 may improve liver function early after transplantation.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shigeshi
authors.initials: S
authors.lastname: Ono
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takayanagi
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanabe
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawachi
authors.forename: Osamu
authors.initials: O
authors.lastname: Itano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinoda
authors.forename: Minoru
authors.initials: M
authors.lastname: Kitago
authors.forename: Taizo
authors.initials: T
authors.lastname: Hibi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Chiba
authors.forename: Wenlin
authors.initials: W
authors.lastname: Du
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Arno W
authors.initials: AW
authors.lastname: Tilles
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Aiso
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
chemical_list: D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein; D007371:Interferon-gamma; D000410:Alanine Transaminase