IL-6 pathway in the liver: From physiopathology to therapy.

Abstract:

:Interleukin 6 (IL-6) is a pleiotropic four-helix-bundle cytokine that exerts multiple functions in the body. In the liver, IL-6 is an important inducer of the acute phase response and infection defense. IL-6 is furthermore crucial for hepatocyte homeostasis and is a potent hepatocyte mitogen. It is not only implicated in liver regeneration, but also in metabolic function of the liver. However, persistent activation of the IL-6 signaling pathway is detrimental to the liver and might ultimately result in the development of liver tumors. On target cells IL-6 can bind to the signal transducing subunit gp130 either in complex with the membrane-bound or with the soluble IL-6 receptor to induce intracellular signaling. In this review we describe how these different pathways are involved in the physiology and pathophyiology of the liver. We furthermore discuss how IL-6 pathways can be selectively inhibited and therapeutically exploited for the treatment of liver pathologies.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Schmidt-Arras D,Rose-John S

doi

10.1016/j.jhep.2016.02.004

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

1403-15

issue

6

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(16)00083-0

journal_volume

64

pub_type

杂志文章,评审
  • Inhibition of hepatitis C virus gene expression by adenoviral vectors encoding antisense RNA in vitro and in vivo.

    abstract:BACKGROUND & AIMS:In this study, adenoviral vectors encoding an antisense RNA complementary to the 5' non-coding region (5'NCR) of the HCV-genome were generated to inhibit HCV-RNA gene expression in cell culture and in vivo. METHODS:First and second-generation (with E4-deletion) adenoviruses encoding the HCV5'NCR in a...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2010.11.010

    authors: González-Carmona MA,Vogt A,Heinicke T,Quasdorff M,Hoffmann P,Yildiz Y,Schneider C,Serwe M,Bartenschlager R,Sauerbruch T,Caselmann WH

    更新日期:2011-07-01 00:00:00

  • Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis.

    abstract:BACKGROUND & AIMS:Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosi...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2010.03.028

    authors: Altorjay I,Vitalis Z,Tornai I,Palatka K,Kacska S,Farkas G,Udvardy M,Harsfalvi J,Dinya T,Orosz P,Lombay B Jr,Par G,Par A,Csak T,Osztovits J,Szalay F,Csepregi A,Lakatos PL,Papp M

    更新日期:2010-09-01 00:00:00

  • Sympathetic nervous activity in cirrhosis. A survey of plasma catecholamine studies.

    abstract::This review summarizes recent progress in the knowledge of catecholamines in cirrhosis. Compensated patients have normal plasma concentration of noradrenaline. Highly elevated plasma noradrenaline concentration in decompensated patients indicates that the sympathetic nervous system is enhanced in this condition. This ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/s0168-8278(85)80068-4

    authors: Henriksen JH,Ring-Larsen H,Christensen NJ

    更新日期:1985-01-01 00:00:00

  • Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma.

    abstract:BACKGROUND/AIMS:The MAGE, GAGE and BAGE genes encode tumor antigens recognized by autologous cytotoxic T lymphocytes. The aim of this study was to evaluate the possibility of using these genes as molecular markers and as the targets of specific immunotherapy for human hepatocellular carcinoma (HCC). METHODS:The expres...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(00)80223-8

    authors: Kobayashi Y,Higashi T,Nouso K,Nakatsukasa H,Ishizaki M,Kaneyoshi T,Toshikuni N,Kariyama K,Nakayama E,Tsuji T

    更新日期:2000-04-01 00:00:00

  • Adaptive changes of hepatic bile salt transport in a model of reversible interruption of the enterohepatic circulation in the rat.

    abstract::The reversibility and time course of the adaptive changes in hepatic bile salt transport related to modifications of the bile salt enterohepatic circulation and bile salt pool size have not been previously studied. For this reason a model of reversible interruption of entero-hepatic circulation was characterized in un...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(05)80182-5

    authors: Accatino L,Hono J,Koenig C,Pizarro M,Rodriguez L

    更新日期:1993-08-01 00:00:00

  • Liver X receptor α (LXRα/NR1H3) regulates differentiation of hepatocyte-like cells via reciprocal regulation of HNF4α.

    abstract:BACKGROUND & AIMS:Hepatocyte-like cells, differentiated from different stem cell sources, are considered to have a range of possible therapeutic applications, including drug discovery, metabolic disease modelling, and cell transplantation. However, little is known about how stem cells differentiate into mature and func...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2014.07.025

    authors: Chen KT,Pernelle K,Tsai YH,Wu YH,Hsieh JY,Liao KH,Guguen-Guillouzo C,Wang HW

    更新日期:2014-12-01 00:00:00

  • The option of HBIG-free prophylaxis against recurrent HBV.

    abstract::Since the early 1990's, hepatitis B immune globulin (HBIG) has been central to the prevention of hepatitis B virus (HBV) recurrence after liver transplantation. When used in combination with oral nucleos(t)ide analogues, HBIG prevents reinfection with HBV in ⩾90% of transplant recipients. While HBIG is highly efficaci...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2011.08.026

    authors: Fox AN,Terrault NA

    更新日期:2012-05-01 00:00:00

  • Long term transgene expression by hepatocytes transduced with retroviral vectors requires induction of immune tolerance to the transgene.

    abstract:BACKGROUND/AIMS:Gene therapy for inherited liver diseases requires permanent expression of the therapeutic gene. However, in vivo liver transduction with retroviral vectors triggers an immune elimination of transduced hepatocytes. Here we investigated whether immune response could be prevented by treatment with compoun...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2004.04.015

    authors: Puppi J,Guillonneau C,Pichard V,Bellodi-Privato M,Cuturi MC,Anegon I,Ferry N

    更新日期:2004-08-01 00:00:00

  • Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet.

    abstract:BACKGROUND/AIMS:The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypot...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2005.08.026

    authors: Igolnikov AC,Green RM

    更新日期:2006-03-01 00:00:00

  • Evidence for selection of hepatitis B mutants after liver transplantation through peripheral blood mononuclear cell infection.

    abstract:BACKGROUND/AIMS:Despite anti-HBs immunoglobulin therapy, hepatitis B virus (HBV) infection recurs in a high proportion of patients transplanted for HBsAg positive and serum HBV DNA negative chronic liver disease. The contribution of HBV genetic variability to disease recurrence has not been yet thoroughly addressed. We...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(97)80035-9

    authors: Brind A,Jiang J,Samuel D,Gigou M,Feray C,Bréchot C,Kremsdorf D

    更新日期:1997-02-01 00:00:00

  • A specific immune response to purified HA antigen (HAAg) demonstrated by leukocyte migration inhibition in patients recovering from viral hepatitis A.

    abstract::The mechanism responsible for liver cell necrosis in patients with hepatitis A is not known. Since the type of hepatic lesions and the clinical presentation of acute hepatitis B are similar and are probably related to the cell-mediated immune response to a viral antigen located in the liver cell, it is possible that a...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(86)80082-4

    authors: Fasel-Folley J,Overby LR,Frei PC

    更新日期:1986-01-01 00:00:00

  • Infection with a novel human DNA virus (TTV) has no pathogenic significance in patients with liver diseases.

    abstract:BACKGROUND/AIMS:A recently identified DNA virus, termed TT virus (TTV), has been associated with post-transfusional hepatitis, and a high prevalence of TTV infection in patients with acute or chronic liver disease of unknown etiology has been reported from Japan, but few data are available about TTV infection in other ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(99)80256-6

    authors: Giménez-Barcons M,Forns X,Ampurdanés S,Guilera M,Soler M,Soguero C,Sánchez-Fueyo A,Mas A,Bruix J,Sánchez-Tapias JM,Rodés J,Saiz JC

    更新日期:1999-06-01 00:00:00

  • Treatment of alcohol use disorders in patients with alcoholic liver disease.

    abstract::Alcohol use disorders (AUDs) is one of the leading causes of disease and disability in almost all European countries. Among the alcohol-related diseases, alcoholic liver disease (ALD) is the most common. At present, alcohol is the most frequent cause of liver cirrhosis in the Western world. The cornerstone of treatmen...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2016.04.029

    authors: Addolorato G,Mirijello A,Barrio P,Gual A

    更新日期:2016-09-01 00:00:00

  • Long-term follow-up after liver transplantation for autoimmune hepatitis: evidence of recurrence of primary disease.

    abstract:BACKGROUND/AIMS:After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown. METHODS:In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8....

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(99)80017-8

    authors: Ratziu V,Samuel D,Sebagh M,Farges O,Saliba F,Ichai P,Farahmand H,Gigou M,Féray C,Reynès M,Bismuth H

    更新日期:1999-01-01 00:00:00

  • Hepatic B cell leukemia-3 promotes hepatic steatosis and inflammation through insulin-sensitive metabolic transcription factors.

    abstract:BACKGROUND & AIMS:The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-κB)-cofactor gene B cell leukemia-3 (Bcl-3) plays a critical role in altering the transcriptional capacity of NF-κB - a key inducer o...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2016.06.026

    authors: Gehrke N,Wörns MA,Huber Y,Hess M,Straub BK,Hövelmeyer N,Waisman A,Kim YO,Schuppan D,Galle PR,Schattenberg JM

    更新日期:2016-12-01 00:00:00

  • Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase.

    abstract:BACKGROUND & AIMS:Glucagon-like peptide-1 (GLP-1), a gut-derived peptide degraded by dipeptidyl peptidase-4 (DPP4), stimulates insulin secretion in response to nutrients, yet its direct effect on the liver is controversial. We investigated the effects of GLP-1 on hepatic fat and glucose metabolism and elucidated its me...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2010.09.032

    authors: Ben-Shlomo S,Zvibel I,Shnell M,Shlomai A,Chepurko E,Halpern Z,Barzilai N,Oren R,Fishman S

    更新日期:2011-06-01 00:00:00

  • Prolonged QTc interval and its relationship to autonomic cardiovascular reflexes in patients with cirrhosis.

    abstract:BACKGROUND/AIMS:We have previously shown that an abnormality in cardiac autonomic reflexes (AN) is an independent predictor of mortality in patients with chronic liver disease. Aim of this study was to determine whether there was an association between prolonged QTc interval and cardiac AN. METHODS:Cardiac AN and QTc ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(01)00217-3

    authors: Puthumana L,Chaudhry V,Thuluvath PJ

    更新日期:2001-12-01 00:00:00

  • Defective aggregation in cirrhosis is independent of in vivo platelet activation.

    abstract:BACKGROUND/AIMS:Platelet function abnormalities contribute to the hemostatic defect in patients with cirrhosis. In this study we evaluated the occurrence of in vivo platelet activation as a possible mechanism of defective platelet aggregation in patients with cirrhosis. METHODS:Nine patients with severe (Child B-C) ci...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(96)80164-4

    authors: Laffi G,Cinotti S,Filimberti E,Ciabattoni G,Caporale R,Marra F,Melani L,Grossi A,Carloni V,Gentilini P

    更新日期:1996-04-01 00:00:00

  • Long-term native liver fibrosis in biliary atresia: development of a novel scoring system using histology and standard liver tests.

    abstract:BACKGROUND & AIMS:Although liver fibrosis is an important predictor of outcomes for biliary atresia (BA), postsurgical native liver histology has not been well reported. Here, we retrospectively evaluated postsurgical native liver histology, and developed and assessed a novel scoring system - the BA liver fibrosis (BAL...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2014.01.028

    authors: Tomita H,Masugi Y,Hoshino K,Fuchimoto Y,Fujino A,Shimojima N,Ebinuma H,Saito H,Sakamoto M,Kuroda T

    更新日期:2014-06-01 00:00:00

  • Behavior and significance of autoantibodies in type 1 autoimmune hepatitis.

    abstract:BACKGROUND/AIM:Smooth muscle antibodies and antinuclear antibodies characterize type 1 autoimmune hepatitis. Our aim was to correlate the appearance and disappearance of these autoantibodies with clinical and histological events. METHODS:One hundred and seven patients were evaluated successively over 128+/-9 months. A...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(99)80096-8

    authors: Czaja AJ

    更新日期:1999-03-01 00:00:00

  • The mitogenic activity of the liver growth factor is mediated by tumor necrosis factor alpha in rat liver.

    abstract:BACKGROUND/AIMS:Liver growth factor (LGF) is a hepatic mitogen, however, the hepatic stimulation pathway remains to be characterized. The aim of this study was to determine whether tumor necrosis factor alpha (TNF-alpha) stimulation constitutes a step in the mitogenic pathway of LGF. METHODS:Rats were injected with 4....

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(03)00030-8

    authors: Díaz-Gil JJ,Majano PL,López-Cabrera M,Sánchez-López V,Rúa C,Machín C,Trilla C,García-Cañero R,Moreno-Otero R

    更新日期:2003-05-01 00:00:00

  • Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum.

    abstract:BACKGROUND/AIMS:Lipid peroxidation has been found to be associated with Ito cell activation. Ito cells are the principal collagen-producing cells and the main storage sites of retinoids. However, the relationship between retinoids and hepatic fibrosis is complex. The aim of this study was to elucidate the role of retin...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(98)80121-9

    authors: Mizobuchi Y,Shimizu I,Yasuda M,Hori H,Shono M,Ito S

    更新日期:1998-12-01 00:00:00

  • Characteristics of patients with dual infection by hepatitis B and C viruses.

    abstract:BACKGROUND/AIMS:The purpose of this study was to compare the epidemiological, biochemical, virological and histological characteristics of patients with chronic hepatitis B and C with those of patients suffering from chronic hepatitis C alone. METHODS:Twenty-three patients with chronic hepatitis C, who were anti-HCV p...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(98)80198-0

    authors: Zarski JP,Bohn B,Bastie A,Pawlotsky JM,Baud M,Bost-Bezeaux F,Tran van Nhieu J,Seigneurin JM,Buffet C,Dhumeaux D

    更新日期:1998-01-01 00:00:00

  • Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study.

    abstract:BACKGROUND/AIMS:To assess the efficacy and safety of naltrexone for the short and long term treatment of pruritus of cholestasis. METHODS:Twenty patients with pruritus and cholestasis were included. A baseline pruritus score was obtained over 1 week. Patients were then randomized to receive 50 mg/day of naltrexone or ...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0168-8278(02)00318-5

    authors: Terg R,Coronel E,Sordá J,Muñoz AE,Findor J

    更新日期:2002-12-01 00:00:00

  • In vivo silencing of Reptin blocks the progression of human hepatocellular carcinoma in xenografts and is associated with replicative senescence.

    abstract:BACKGROUND & AIMS:We previously showed that Reptin is overexpressed in hepatocellular carcinoma (HCC), and that in vitro depletion of Reptin with siRNAs led to HCC cell growth arrest and apoptosis. Here, we asked whether in vivo targeting of Reptin in established tumours had a therapeutic effect. METHODS:We used lenti...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2009.12.029

    authors: Ménard L,Taras D,Grigoletto A,Haurie V,Nicou A,Dugot-Senant N,Costet P,Rousseau B,Rosenbaum J

    更新日期:2010-05-01 00:00:00

  • A patient with novel ABCB11 gene mutations with phenotypic transition between BRIC2 and PFIC2.

    abstract::We describe a PFIC2 patient with a good response to ursodeoxycholic acid for 9 years. We found two novel ABCB11 gene mutations in the patient, i.e. I498T and 2098delA. The correlation of the patient's genotypes with the clinical course supports the existence of a phenotypic continuum between BRIC2 and PFIC2. ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2005.09.013

    authors: Lam CW,Cheung KM,Tsui MS,Yan MS,Lee CY,Tong SF

    更新日期:2006-01-01 00:00:00

  • Management of anemia induced by triple therapy in patients with chronic hepatitis C: challenges, opportunities and recommendations.

    abstract::The addition of protease inhibitors, boceprevir or telaprevir, to peginterferon+ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with a...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2013.07.014

    authors: Romero-Gómez M,Berenguer M,Molina E,Calleja JL

    更新日期:2013-12-01 00:00:00

  • Interferon-γ-dependent immune responses contribute to the pathogenesis of sclerosing cholangitis in mice.

    abstract:BACKGROUND AND AIMS:Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver disorder characterized by biliary inflammation and fibrosis. Increased numbers of intrahepatic interferon-γ- (IFNγ) producing lymphocytes have been documented in patients with PSC, yet their functional role remains to b...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2019.05.023

    authors: Ravichandran G,Neumann K,Berkhout LK,Weidemann S,Langeneckert AE,Schwinge D,Poch T,Huber S,Schiller B,Hess LU,Ziegler AE,Oldhafer KJ,Barikbin R,Schramm C,Altfeld M,Tiegs G

    更新日期:2019-10-01 00:00:00

  • Bone disease in patients with primary sclerosing cholangitis: prevalence, severity and prediction of progression.

    abstract:BACKGROUND/AIMS:Osteopenia is a common complication in some chronic cholestatic liver diseases. Our aims were to determine the prevalence and severity of bone disease in patients with primary sclerosing cholangitis; and identify risk factors to predict the presence and progression of osteopenia. METHODS:Eighty-one pat...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0168-8278(98)80253-5

    authors: Angulo P,Therneau TM,Jorgensen A,DeSotel CK,Egan KS,Dickson ER,Hay JE,Lindor KD

    更新日期:1998-11-01 00:00:00

  • Effect of amphotericin B on hepatic cytochrome P-450 and glucose-6-phosphatase in the rat.

    abstract::The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentration...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/0168-8278(92)90174-n

    authors: Heidemann H,Holzlöhner U,Heydemann J,Freitag T,Inselmann G

    更新日期:1992-03-01 00:00:00