Interleukin 18--binding protein ameliorates liver ischemia--reperfusion injury

Ahmet Bal; Yucel Gonul; Omer Hazman; Ahmet Kocak; Mehmet Fatih Bozkurt; Sezgin Yilmaz; Serdar Kokulu; Oya Oruc; Kasim Demir

doi:10.1016/j.jss.2015.10.008

Interleukin 18--binding protein ameliorates liver ischemia--reperfusion injury

J Surg Res. 2016 Mar;201(1):13-21. doi: 10.1016/j.jss.2015.10.008. Epub 2015 Oct 12.

Authors

Ahmet Bal¹, Yucel Gonul², Omer Hazman³, Ahmet Kocak⁴, Mehmet Fatih Bozkurt⁵, Sezgin Yilmaz⁶, Serdar Kokulu⁷, Oya Oruc⁸, Kasim Demir⁹

Affiliations

¹ Department of General Surgery, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey. Electronic address: cerrahdoktor@gmail.com.
² Department of Anatomy, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
³ Department of Biochemistry, Faculty of Science and Arts, Afyon Kocatepe University, Afyonkarahisar, Turkey.
⁴ Department of Histology and Embryology, Faculty of Medicine, Dumlupinar University, Kütahya, Turkey.
⁵ Department of Pathology, Faculty of Veterinary, Afyon Kocatepe University, Afyonkarahisar, Turkey.
⁶ Department of General Surgery, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
⁷ Department of Anesthesia and Reanimation, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
⁸ Department of Emergency Medicine, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
⁹ Department of Gastroenterology, Samsun Training and Education Hospital, Samsun, Turkey.

PMID: 26850179
DOI: 10.1016/j.jss.2015.10.008

Abstract

Background: The aim of this study was to investigate the possible protective effect of interleukin 18-binding protein (IL-18BP) on ischemia-reperfusion (I/R)-induced liver injury in experimental rat models. Liver is one of the most affected organs from I/R process. IL-18 is an important proinflammatory cytokine, which may induce some events such as production of reactive oxygen substances and release of various cytokines. IL-18BP acts as an inhibitor of IL-18. The relationship between IL-18 and IL-18BP has an important place in inflammatory process.

Materials and methods: Rats were equally divided into three groups as follows: sham: Hepatic pedicle dissection was done, but hepatic pedicle clamping was not used. I/R: Sixty minutes of ischemia and 2 h of reperfusion were applied. IR + IL-18BP: Recombinant human IL-18BP (100 μg/kg) was administered 30 min before the surgery. Hepatic pedicle was clamped during 60 min of ischemia and 2 h of reperfusion was achieved.

Results: Liver enzyme levels were significantly lower in the IR + IL-18BP group, when compared with the I/R group. Serum and tissue levels of tumor necrosis factor-α, IL-6, and IL-18 were considerably lower in the IR + IL-18BP group, when compared with the I/R group, but hepatic interferon-γ and IL1β levels were not significant. Serum oxidative stress index level was significantly higher in the I/R group, when compared with the IR + IL-18BP group. In immunostaining, it was observed that pathologic changes were lower in IR + IL-18BP group than the I/R group.

Conclusions: IL-18BP exhibited anti-inflammatory, antioxidant, and protective effects in I/R-mediated hepatic injury via regulating some liver enzyme activities and cytokine levels. Additionally, these effects have been verified by histomorphologic examination and oxidative stress markers.

Keywords: IL-18; IL-18 binding protein; Ischemia; Liver; Reperfusion injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines / blood
Drug Evaluation, Preclinical
Immunohistochemistry
Intercellular Signaling Peptides and Proteins / therapeutic use*
Liver / blood supply*
Liver / enzymology
Liver / pathology
Male
Oxidative Stress
Rats, Wistar
Reperfusion Injury / blood
Reperfusion Injury / drug therapy*
Reperfusion Injury / pathology

Substances

Cytokines
Intercellular Signaling Peptides and Proteins
interleukin-18 binding protein