Interleukin 18–binding protein ameliorates liver ischemia–reperfusion injury

Bal, Ahmet; Gönül, Yücel; Hazman, Ömer; Koçak, Ahmet; Bozkurt, Mehmet Fatih; Yılmaz, Sezgin; Kokulu, Serdar; Oruç, Oya Akpınar; Demir, Kasım

doi:10.1016/j.jss.2015.10.008

Cited by 7 publications

(3 citation statements)

References 44 publications

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“…Takeuchi et al showed a significant reduction of IRI and a concomitant upregulation of anti-inflammatory cytokines such as IL-4 and IL-10 in a mice model under blockade of IL-18 [26]. In line with these results, Bal et al demonstrated a protective effect of IL-18binding protein on IRI induced liver injury in an experimental rat model [27]. Of note, our data showed similar kinetics of IL-18 and GGT perfusate concentrations (early increase, peak after 2 hours and decrease during ongoing perfusion) after prolonged SCS suggesting an association between IL-18 secretion and bile duct inflammation or injury.…”

Section: Discussionmentioning

confidence: 79%

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Beetz¹,

Cammann²,

Weigle³

et al. 2022

Transpl Int

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In the era of organ machine perfusion, experimental models to optimize reconditioning of (marginal) liver grafts are needed. Although the relevance of cytokine signatures in liver transplantation has been analyzed previously, the significance of molecular monitoring during normothermic machine perfusion (NMP) remains elusive. Therefore, we developed a porcine model of cold ischemic liver graft injury after prolonged static cold storage (SCS) and subsequent NMP: Livers obtained from ten minipigs underwent NMP for 6 h directly after procurement (control group) or after 20 h of SCS. Grafts after prolonged SCS showed significantly elevated AST, ALT, GLDH and GGT perfusate concentrations, and reduced lactate clearance. Bile analyses revealed reduced bile production, reduced bicarbonate and elevated glucose concentrations after prolonged SCS. Cytokine analyses of graft perfusate simultaneously demonstrated an increase of pro-inflammatory cytokines such as Interleukin-1α, Interleukin-2, and particularly Interleukin-18. The latter was the only significantly elevated cytokine compared to controls, peaking as early as 2 h after reperfusion (11,012 ng/ml vs. 1,493 ng/ml; p = 0.029). Also, concentrations of High-Mobility-Group-Protein B1 were significantly elevated after 2 h of reperfusion (706.00 ng/ml vs. 148.20 ng/ml; p < 0.001) and showed positive correlations with AST (r2 = 0.846) and GLDH (r2 = 0.918) levels. Molecular analyses during reconditioning of liver grafts provide insights into the degree of inflammation and cell damage and could thereby facilitate future interventions during NMP reducing acute and chronic graft injury.

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Section: Discussionmentioning

confidence: 79%

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Beetz¹,

Cammann²,

Weigle³

et al. 2022

Transpl Int

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“…This indicates that the combination therapy of erythropoietin and methylprednisolone has advantages in inhibiting IL-1 and IL-8 and promoting IL-1RA, thereby ensuring better preservation of spinal nerve function. Moreover, these studies show that the combination of erythropoietin and methylprednisolone can significantly improve the quality of life of patients compared to therapy involving methylprednisolone alone [25,26].…”

Section: Discussionmentioning

confidence: 96%

The Efficacy of Combined Medication With Methylprednisolone and Erythropoietin in the Treatment of Ischemia-Reperfusion Injury to the Spinal Cord in Patients With Cervical Spondylotic Myelopathy

Eryilmaz¹,

Farooque²

2021

Cureus

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Introduction Cervical myelopathy (CM) is caused by degenerative or congenital changes in the discs and soft tissues of the cervical spine, leading to chronic compression of the spinal cord. The current treatment for moderate-tosevere CM is surgical decompression, which is effective in most cases; however, it can cause inflammation of the nervous system and spinal cord reperfusion injury, resulting in perioperative neurological complications and suboptimal neurological recovery. The aim of this study was to investigate the therapeutic effects of the combination of erythropoietin and methylprednisolone in the treatment of ischemia-reperfusion injury to the spinal cord and to analyze its effects on the levels of interleukin-1 beta (IL-1β), interleukin-1 receptor antagonist (IL-1RA), and interleukin-8 (IL-8). Materials and methods This study included 110 patients admitted to the hospital due to cervical spondylotic myelopathy. They were randomized into two groups of 55 patients each: a control and an observation group. In both groups of patients, fusion internal fixation and anterior cervical discectomy were performed. The difference, however, was that the control group received a rapid intravenous injection of 30 mg/kg methylprednisolone 30 minutes prior to spinal cord decompression, while the observation group received an intravenous injection of 30 mg/kg methylprednisolone and 3,000 U/kg erythropoietin 30 minutes before spinal cord decompression. The study was approved by the Hospital Ethical Committee of the Dow University of Health Sciences, Karachi. The neurological function of both groups of patients was assessed before the procedure and three months after the treatment using the Japanese Orthopedic Association (JOA) method of assessing spinal cord function (40-point rating method). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of neuron-specific enolase (NSE), S-100β, IL-1RA, IL-1β, and IL-8 in both groups. The quality of life of patients in both groups was assessed three months after the treatment with the World Health Organization Quality of Life assessment instrument (WHOQOL-100). Results Before the treatment, there was no significant variance between the two groups in the JOA score and the 40point rating method. Similarly, there was no significant difference in the levels of IL-1β, IL-1RA, and IL-8 between the two groups (p-value = 0.262, 0.387, and 0.154 respectively) prior to the treatment. Three months after the treatment, the levels of IL-1β and IL-8 in the observation group were 21.83 ±3.65 ng/l and 357.07 ±32.36 ng/l respectively, both lower than the control group value (p-value = 0.026, 0.028 respectively). The level of IL-1RA in follow-up was 21.59 ±1.15 ng/l, which was higher than that in the control group. Three months after the treatment, all the WHOQOL-100 parameters of the observation group for psychology, physiology, social relations, independence, spirituality, environment, and general quality of life were higher than those of the control group; the variance ...

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“…The pathologic results revealed that a smaller hepatic artery diameter and a depressed vessel wall were observed at 30 minutes after reperfusion in the control group, and these results were not detected in other groups . This finding also provides strong evidence of the occurrence of a hepatic artery spasm.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hepatic Artery Spasm on a Rat Model of Hepatic Ischemia‐Reperfusion Injury

Tang

et al. 2018

J of Ultrasound Medicine

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Objectives To investigate hemodynamic changes in the hepatic artery after hepatic ischemia‐reperfusion injury (IRI) in rats via ultrasound (US) imaging and to discuss the protective effect of phentolamine (PHT) pretreatment on hepatic IRI. Methods Fifty rats were randomly divided into 3 groups: a sham operation group (n = 10), a control ischemia‐reperfusion group (n = 20), and a PHT pretreatment group (n = 20). Color Doppler flow imaging and contrast‐enhanced US examinations were performed in each group at 30 minutes (n = 10) and 90 minutes (n = 10) after reperfusion. Blood samples were obtained to analyze serum alanine aminotransferase and aspartate aminotransferase levels, and liver tissue specimens were collected for pathologic analysis. Results Using US, we found that hepatic artery resistance at 30 minutes after reperfusion in the control group was higher than that in the sham group (mean resistive index [RI] ± SD, 0.65 ± 0.09 versus 0.50 ± 0.09; P < .01), which was higher at 30 than 90 minutes (RI, 0.65 ± 0.09 versus 0.50 ± 0.08; P < .01) after reperfusion in the control group. However, the hepatic artery resistance and liver microcirculation in the PHT group were better than those in the control group at 30 minutes after reperfusion (RI, 0.54 ± 0.09 versus 0.65 ± 0.09; P < .05; time to peak, 31.94 ± 2.02 versus 48.34 ± 4.74 seconds; P < .01). Compared to the control group, the aspartate aminotransferase and alanine aminotransferase levels were significantly lower at 30 minutes after reperfusion in the PHT group (P < .05). A pathologic examination revealed a smaller hepatic artery diameter and a depressed vessel wall in the control group. Conclusions The hepatic artery can undergo a transient spasm during the hepatic IRI process, which can exacerbate liver damage. Phentolamine treatment can alleviate hepatic artery spasms, improve liver perfusion, and reduce liver injury by ameliorating the hepatic microcirculation.

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Interleukin 18–binding protein ameliorates liver ischemia–reperfusion injury

Cited by 7 publications

References 44 publications

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

The Efficacy of Combined Medication With Methylprednisolone and Erythropoietin in the Treatment of Ischemia-Reperfusion Injury to the Spinal Cord in Patients With Cervical Spondylotic Myelopathy

Effect of Hepatic Artery Spasm on a Rat Model of Hepatic Ischemia‐Reperfusion Injury

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