title: Interleukin 18 binding protein ameliorates ischemia/reperfusion-induced hepatic injury in mice.
abstract: Inflammation-associated oxidative stress contributes to hepatic ischemia/reperfusion injury (IRI). Detrimental inflammatory event cascades largely depend on activated Kupffer cells (KCs) and neutrophils, as well as proinflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL) 18. The aim of our study was to evaluate the effects of IL 18 binding protein (IL 18Bp) in hepatic IRI of mice. Thirty C57BL/6 mice were allocated into 3 groups: sham operation, ischemia/reperfusion (I/R), and I/R with intravenous administration of IL 18Bp. Hepatic ischemia was induced for 30 minutes by Pringle's maneuver. After 120 minutes of reperfusion, mice were euthanized, and the liver and blood samples were collected for histological, immunohistochemical, molecular, and biochemical analyses. I/R injury induced the typical liver pathology and upregulated IL-18 expression in the liver of mice. Binding of IL 18 with IL 18Bp significantly reduced the histopathological indices of I/R liver injury and KC apoptosis. The I/R-induced increase of TNF-α, malondialdehyde, aspartate aminotransferase, and alanine aminotransferase levels was prevented in statistically significant levels because of the pretreatment with IL 18Bp. Likewise, blocking of IL 18 ablated the I/R-associated elevation of nuclear factor kappa B, c-Jun, myeloperoxidase, and IL 32 and the up-regulation of neutrophils and T-helper lymphocytes. Administration of IL 18Bp protects the mice liver from I/R injury by intervening in critical inflammation-associated pathways and KC apoptosis.
authors.affiliation: Division of Transplant Surgery, Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Ouzounidis
authors.affiliation: Division of Transplant Surgery, Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Giakoustidis
authors.affiliation: Laboratory of Pathology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Theofilos
authors.initials: T
authors.lastname: Poutahidis
authors.affiliation: Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Thessaloniki, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Angelopoulou
authors.affiliation: Laboratory of Biochemistry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Iliadis
authors.affiliation: Laboratory of Pathology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Chatzigiagkos
authors.affiliation: Experimental and Research Center ELPEN Pharmaceuticals, Athens, Greece.
authors.forename: Argyro
authors.initials: A
authors.lastname: Zacharioudaki
authors.affiliation: 4th Division of Surgery, Department of Surgery, School of Health Sciences, Aristotle University of Thessaloniki and Hippokration General Hospital, Thessaloniki, Greece.
authors.forename: Stamatis
authors.initials: S
authors.lastname: Angelopoulos
authors.affiliation: Experimental and Research Center ELPEN Pharmaceuticals, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.affiliation: Division of Transplant Surgery, Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Papanikolaou
authors.affiliation: Division of Transplant Surgery, Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Giakoustidis
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D020382:Interleukin-18 / Q000378:metabolism; D008099:Liver / Q000293:injuries* / Q000378:metabolism; D008107:Liver Diseases / Q000628:therapy*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; C118370:interleukin-18 binding protein; D008315:Malondialdehyde; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase