IL‐2/IL‐6 ratio correlates with liver function and recovery in acute liver injury patients

Sun, Yu; Gu, Jian; Liu, Rui; Zhou, Haoming; Lü, Ling; Dai, Xinzheng; Qian, Xin

doi:10.1111/apm.12944

Cited by 10 publications

(3 citation statements)

References 29 publications

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“…Steuerwald et al claimed that low serum levels of IL-9 and IL-17 predict early death caused by drug-induced liver injury [26]. Sun's study has confirmed that the change of IL-2/IL-6 ratio is often used as an evaluation index of liver function recovery in patients with acute liver injury [27]. Data from this study suggested that early IL-6 level is an important marker of advanced liver function in pregnant women with hepatitis B.…”

Section: Discussionmentioning

confidence: 98%

Predictive Value of Inflammatory Cytokines in Early Pregnancy for Liver Dysfunction in Pregnant Women with Hepatitis B

et al. 2022

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The purpose of this study is to explore the predictive value of cytokine levels in the first trimester of pregnancy on abnormal liver function of pregnant women with hepatitis B in the third trimester of pregnancy. A total of 111 pregnant women with HBV infection at 12 weeks gestation participated in the study. The levels of IL-6, IL-8, TNF-α in peripheral blood of the patients and liver function indexes were detected. Subsequently, the pregnant women were followed up, and the liver function was detected at 36 weeks of gestation. According to liver function indexes, patients were divided into normal liver function group and abnormal liver function group to determine the correlation between cytokines in early pregnancy and abnormal liver function in late pregnancy. Kaplan–Meier survival curve and multivariate Cox analysis were used to evaluate the predictive value of cytokines for liver dysfunction. At 12 weeks of gestation, cytokine levels in the normal liver function group were significantly lower than that in the abnormal liver function group. Kaplan–Meier survival analysis showed that the increased IL-6 level was associated with abnormal liver function in late pregnancy. Multivariate Cox regression analysis revealed that IL-6 level was an independent predictor of abnormal liver function in patients with normal liver function in the late pregnancy. The high expression level of cytokine IL-6 at 12 weeks of pregnancy has noteworthy predictive significance for the abnormal liver function of hepatitis B pregnant women in third trimester of pregnancy.

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Section: Discussionmentioning

confidence: 98%

Predictive Value of Inflammatory Cytokines in Early Pregnancy for Liver Dysfunction in Pregnant Women with Hepatitis B

et al. 2022

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“…However, uncontrolled immunity, triggered by acute phase factors, can lead to liver injury [9]. IL-6 induces the expression of IL-17 and promotes hepatocyte apoptosis, thus aggravating liver damage [10]. Li's study suggests that reducing IL-6 is beneficial to attenuating ethanol-induced liver injury [11].…”

Section: Introductionmentioning

confidence: 99%

IL-6 Mutation Attenuates Liver Injury Caused by Aeromonas hydrophila Infection by Reducing Oxidative Stress in Zebrafish

Zhai,

Wang,

et al. 2023

IJMS

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Interleukin-6 (IL-6), a pleiotropic cytokine, plays a crucial role in acute stress induced by bacterial infection and is strongly associated with reactive oxygen species (ROS) production. However, the role of IL-6 in the liver of fish after Aeromonas hydrophila infection remains unclear. Therefore, this study constructed a zebrafish (Danio rerio) il-6 knockout line by CRISPR/Cas9 to investigate the function of IL-6 in the liver post bacterial infection. After infection with A. hydrophila, pathological observation showed that il-6−/− zebrafish exhibited milder liver damage than wild-type (WT) zebrafish. Moreover, liver transcriptome sequencing revealed that 2432 genes were significantly up-regulated and 1706 genes were significantly down-regulated in il-6−/− fish compared with WT fish after A. hydrophila infection. Further, gene ontology (GO) analysis showed that differentially expressed genes (DEGs) were significantly enriched in redox-related terms, including oxidoreductase activity, copper ion transport, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in pathways such as the PPAR signaling pathway, suggesting that il-6 mutation has a significant effect on redox processes in the liver after A. hydrophila infection. Additionally, il-6−/− zebrafish exhibited lower malondialdehyde (MDA) levels and higher superoxide dismutase (SOD) activities in the liver compared with WT zebrafish following A. hydrophila infection, indicating that IL-6 deficiency mitigates oxidative stress induced by A. hydrophila infection in the liver. These findings provide a basis for further studies on the role of IL-6 in regulating oxidative stress in response to bacterial infections.

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“…Interleukin-6 (IL-6) plays a key role in the occurrence and development of liver diseases and the effects vary in different periods of disease progression [10]. At the early stage of ALD, high levels of IL-6 in serum suggest a good prognosis, and in hepatocytes, its downstream signal transducer and activator of transcription 3 (STAT3) activation ensues to regulate various hepatocyte-protective genes to reduce inflammatory response; however, high levels of serum IL-6 serve as a poor prognostic indicator for patients at the terminal stage of ALD [11,12]. Therefore, targeting IL-6 and its related signaling pathways in the liver could hint at a new target for the diagnosis and treatment of liver disease.…”

Section: Introductionmentioning

confidence: 99%

Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6–p47phox Oxidative–Stress Axis

Cui

Xue

et al. 2022

Cells

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(1) Background: To explore the effect of exercise on the formation and recovery of alcoholic liver disease (ALD) and whether the IL-6–p47phox oxidative–stress axis is involved in that process. (2) Methods: Firstly, 23 six-week-old male C57BL/6J mice were randomly divided into the Con group, ALD group, ALD + NOXI group, ALD + Ex group, and ALD + Ex + NOXI group. The Liber–DeCarli alcoholic liquid diet was used for 6 weeks to establish the ALD mice model, and the Con group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet, and exercise intervention was started after the ALD model establishment and lasted for another 6 weeks, with or without administration of the NOX inhibitor apocynin by intraperitoneal injection on every exercise training day. Secondly, 28 mice were randomly divided into the Sed group, Eth group, Eth + Ex group and Eth + Ex + NOXI group. The Sed group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet and exercise intervention was started synchronously combined with or without administration of intraperitoneal apocynin injections on every exercise training day for 5 weeks. After each individual experiment was accomplished, physiological assessment and biochemical analysis of blood and tissue samples were examined. (3) Results: The levels of TG in serum and IL-6 protein content in liver tissue in the ALD group were significantly increased compared to the Con group (p < 0.05); compared with ALD, p47phox expression in muscle was increased significantly in the ALD + NOXI group (p < 0.05), and TG in serum decreased in the ALD + Ex group (p < 0.05). TG in serum, AST/ALT ratio, and IL-6 content in both liver and muscle decreased (p < 0.05) in the ALD + Ex + NOXI group with MDA in muscle significantly increased (p < 0.01). The AST/ALT ratio, TG in serum, SOD in liver, and p47phox in both liver and muscle in the ALD + Ex + NOXI group were significantly decreased compared with the ALD + NOXI group (p < 0.01). Compared with the ALD + Ex group, the liver index and HDL-C levels in serum were decreased (p < 0.05) in the ALD + Ex + NOXI group. The degree of hepatocyte steatosis and inflammatory infiltration were ameliorated after exercise intervention. In the Eth group, the relative epididymal fat content, HDL-C level, and AST/ALT ratio were significantly decreased, and TG and gp91phox in liver were significantly higher than in the Sed group (p < 0.05, p < 0.01). Compared with the Eth group, the AST/ALT ratio, MDA in the liver, and NOX4 and p47phox protein expression in the liver were significantly increased, and body weight decreased significantly in the Eth + Ex group (p < 0.05, p < 0.01), as did TG in the liver and MDA in muscle. In the th + Ex + NOXI group, gp91phox expression in the liver and body weight were significantly decreased (p < 0.05, p < 0.01). In the Eth + Ex + NOXI group, the ratio of AST/ALT and MDA in muscle were increased when compared with the Eth + Ex group, and the protein expression of gp91phox and p47phox were much lower (p < 0.01). (4) Conclusions: 6 weeks of exercise intervention during the recovery phase of ALD ameliorates hepatocyte damage and dyslipidemia through the IL-6–p47phox oxidative–stress axis, and applying a NOX inhibitor in combination could optimize this. However, drinking alcohol during exercise exacerbates dyslipidemia and oxidative stress, with hepatocyte IL-6–p47phox downregulated.

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IL‐2/IL‐6 ratio correlates with liver function and recovery in acute liver injury patients

Cited by 10 publications

References 29 publications

Predictive Value of Inflammatory Cytokines in Early Pregnancy for Liver Dysfunction in Pregnant Women with Hepatitis B

Predictive Value of Inflammatory Cytokines in Early Pregnancy for Liver Dysfunction in Pregnant Women with Hepatitis B

IL-6 Mutation Attenuates Liver Injury Caused by Aeromonas hydrophila Infection by Reducing Oxidative Stress in Zebrafish

Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6–p47phox Oxidative–Stress Axis

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