Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Emerging Role of Interleukins for the Assessment and Treatment of Liver Diseases

Author(s): Aaliya L. Ali, Namrata P. Nailwal and Gaurav M. Doshi*

Volume 22, Issue 4, 2022

Published on: 26 January, 2022

Page: [371 - 382] Pages: 12

DOI: 10.2174/1871530321666211124102837

Price: $65

Abstract

Background: The most common liver diseases are fibrosis, alcoholic liver disease, nonalcoholic fatty disease, viral hepatitis, and hepatocellular carcinoma. These liver diseases account for approximately 2 million deaths per year worldwide, with cirrhosis accounting for 2.1% of the worldwide burden. The most widely used liver function tests for diagnosis are alanine transaminase, aspartate transaminase, serum proteins, serum albumin, and serum globulins, whereas antivirals and corticosteroids have been proven to be useful for the treatment of liver diseases. A major disadvantage of these diagnostic measures is the lack of specificity to a particular tissue or cell type, as these enzymes are common to one or more tissues. The major adverse effect of current treatment methods is drug resistance. To overcome these issues, interleukins have been investigated. The balance of these interleukins determines the outcome of an immune response. Interleukins are considered interesting therapeutic targets for the treatment of liver diseases. In this review, we summarize the current state of knowledge regarding interleukins in the diagnosis, treatment, and pathogenesis of different acute and chronic liver diseases.

Objective: To understand the role of interleukins in the assessment and treatment of different types of liver diseases.

Methods: A literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: Interleukins, Acute Liver Failure, Alcoholic Liver Disease, Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, Hepatocellular Carcinoma, Inflammation, Liver injury, Hepatoprotective effect. Clinical trial data on these interleukins have been searched on Clinicaltrials.gov.

Results: Existing literature and preclinical and clinical trial data demonstrate that interleukins play a crucial role in the pathogenesis of liver diseases.

Conclusion: Our findings indicate that IL-1, IL-6, IL-10, IL-17, IL-22, IL-35, and IL-37 are involved in the progression and control of various liver conditions via the regulation of cell signaling pathways. However, further investigation on the involvement of these interleukins is necessary for their use as a targeted therapy in liver diseases.

Keywords: Interleukins, acute liver failure, alcoholic liver dsease, non-alcoholic fatty liver disease, liver Fibrosis, hepatocellular carcinoma, inflammation, liver injury, hepatoprotective effect.

Graphical Abstract
[1]
Moore, K.L.; Dalley, A.F.; Agur, A.M.R. Chapter 2: Abdomen. In: Moore Clinically Oriented Anatomy; , 2014.
[2]
Guyton, A.C.; Hall, J.B.B. Guyton and Hall Textbook of Medical Physiology, 13th ed.; Igarss, 2014.
[3]
Heymann, F.; Tacke, F. Immunology in the liver from homeostasis to disease. Nat. Rev. Gastroenterol. Hepatol., 2016, 13(2), 88-110.
[http://dx.doi.org/10.1038/nrgastro.2015.200] [PMID: 26758786]
[4]
Caparrós, E.; Francés, R. The interleukin-20 cytokine family in liver disease. Front. Immunol., 2018, 9, 1155.
[http://dx.doi.org/10.3389/fimmu.2018.01155] [PMID: 29892294]
[5]
Odze, R.D.; Goldblum, J.R. Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas; Elsevier, 2009, p. 1392.
[6]
Kasarala, G.; Tillmann, H.L. Standard liver tests. Clin. Liver Dis., 2016, 8(1), 13-18.
[http://dx.doi.org/10.1002/cld.562] [PMID: 31041056]
[7]
Singh, S.; Osna, N.A.; Kharbanda, K.K. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review. World J. Gastroenterol., 2017, 23(36), 6549-6570.
[http://dx.doi.org/10.3748/wjg.v23.i36.6549] [PMID: 29085205]
[8]
Forrest, E.; Mellor, J.; Stanton, L.; Bowers, M.; Ryder, P.; Austin, A.; Day, C.; Gleeson, D.; O’Grady, J.; Masson, S.; McCune, A.; Patch, D.; Richardson, P.; Roderick, P.; Ryder, S.; Wright, M.; Thursz, M. Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial. Trials, 2013, 14, 262.
[http://dx.doi.org/10.1186/1745-6215-14-262] [PMID: 23958271]
[9]
Singal, A.K.; Walia, I.; Singal, A.; Soloway, R.D. Corticosteroids and pentoxifylline for the treatment of alcoholic hepatitis: Current status. World J. Hepatol., 2011, 3(8), 205-210.
[http://dx.doi.org/10.4254/wjh.v3.i8.205] [PMID: 21954408]
[10]
Fung, S.K.; Andreone, P.; Han, S.H.; Rajender Reddy, K.; Regev, A.; Keeffe, E.B.; Hussain, M.; Cursaro, C.; Richtmyer, P.; Marrero, J.A.; Lok, A.S. Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. J. Hepatol., 2005, 43(6), 937-943.
[http://dx.doi.org/10.1016/j.jhep.2005.05.037] [PMID: 16168522]
[11]
Akdis, M.; Burgler, S.; Crameri, R.; Eiwegger, T.; Fujita, H.; Gomez, E. Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases. J. Allergy Clin. Immunol., 2011, 127, 701-721.
[12]
Mousa, H.S.; Bernuzzi, F.; Invernizzi, P. Cytokines in the Liver: Cytokine Mechanisms in Liver Health and Disease. In: Cytokine Effector Functions in Tissues; , 2017; pp. 75-96.
[http://dx.doi.org/10.1016/B978-0-12-804214-4.00003-8]
[13]
Odeh, M.; Sabo, E.; Srugo, I.; Oliven, A. Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure. Ann. Med., 2005, 37(8), 603-612.
[http://dx.doi.org/10.1080/07853890500317414] [PMID: 16338762]
[14]
Elsing, C.; Harenberg, S.; Stremmel, W.; Herrmann, T. Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated cirrhotic patients. World J. Gastroenterol., 2007, 13(3), 421-425.
[http://dx.doi.org/10.3748/wjg.v13.i3.421] [PMID: 17230612]
[15]
Liu, Q. Role of cytokines in the pathophysiology of acute-on-chronic liver failure. Blood Purif., 2009, 28(4), 331-341.
[http://dx.doi.org/10.1159/000232940] [PMID: 19729901]
[16]
Riordan, SM.; Williams, R. Mechanisms of hepatocyte injury, multiorgan failure, and prognostic criteria in acute liver failure. InSeminars in liver disease., 2003, 23, 203-216.
[17]
Luedde, T.; Liedtke, C.; Manns, M.P.; Trautwein, C. Losing balance: cytokine signaling and cell death in the context of hepatocyte injury and hepatic failure. Eur. Cytokine Netw., 2002, 13(4), 377-383.
[PMID: 12517715]
[18]
Reddy, S.A.; Chaturvedi, M.M.; Darnay, B.G.; Chan, H.; Higuchi, M.; Aggarwal, B.B. Reconstitution of nuclear factor kappa B activation induced by tumor necrosis factor requires membrane-associated components. Comparison with pathway activated by ceramide. J. Biol. Chem., 1994, 269(41), 25369-25372.
[http://dx.doi.org/10.1016/S0021-9258(18)47258-4] [PMID: 7929233]
[19]
Doughty, L.; Clark, R.S.; Kaplan, S.S.; Sasser, H.; Carcillo, J. sFas and sFas ligand and pediatric sepsis-induced multiple organ failure syndrome. Pediatr. Res., 2002, 52(6), 922-927.
[http://dx.doi.org/10.1203/00006450-200212000-00018] [PMID: 12438671]
[20]
Cui, K.; Yan, G.; Xu, C.; Chen, Y.; Wang, J.; Zhou, R.; Bai, L.; Lian, Z.; Wei, H.; Sun, R.; Tian, Z. Invariant NKT cells promote alcohol-induced steatohepatitis through interleukin-1β in mice. J. Hepatol., 2015, 62(6), 1311-1318.
[http://dx.doi.org/10.1016/j.jhep.2014.12.027] [PMID: 25582105]
[21]
Kammüller, M.E. Recombinant human interleukin-6: safety issues of a pleiotropic growth factor. Toxicology, 1995, 105(1), 91-107.
[http://dx.doi.org/10.1016/0300-483X(95)03128-3] [PMID: 8638288]
[22]
Lok, A.S.F. Hepatitis B infection: pathogenesis and management. J. Hepatol., 2000, 32(1)(Suppl.), 89-97.
[http://dx.doi.org/10.1016/S0168-8278(00)80418-3] [PMID: 10728797]
[23]
Tilg, H.; Moschen, A.R.; Szabo, G. Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology, 2016, 64(3), 955-965.
[http://dx.doi.org/10.1002/hep.28456] [PMID: 26773297]
[24]
Kuna, L.; Jakab, J.; Smolic, R.; Raguz-Lucic, N.; Vcev, A.; Smolic, M. Peptic ulcer disease: a brief review of conventional therapy and herbal treatment options. J. Clin. Med., 2019, 8(2), 179.
[http://dx.doi.org/10.3390/jcm8020179] [PMID: 30717467]
[25]
Bracey, N.A.; Beck, P.L.; Muruve, D.A.; Hirota, S.A.; Guo, J.; Jabagi, H.; Wright, J.R., Jr; Macdonald, J.A.; Lees-Miller, J.P.; Roach, D.; Semeniuk, L.M.; Duff, H.J. The Nlrp3 inflammasome promotes myocardial dysfunction in structural cardiomyopathy through interleukin-1β. Exp. Physiol., 2013, 98(2), 462-472.
[http://dx.doi.org/10.1113/expphysiol.2012.068338] [PMID: 22848083]
[26]
Lee, S.; Margolin, K. Cytokines in cancer immunotherapy. Cancers (Basel), 2011, 3(4), 3856-3893.
[http://dx.doi.org/10.3390/cancers3043856] [PMID: 24213115]
[27]
Vatrella, A.; Fabozzi, I.; Calabrese, C.; Maselli, R.; Pelaia, G. Dupilumab: a novel treatment for asthma. J. Asthma Allergy, 2014, 7, 123-130.
[http://dx.doi.org/10.2147/JAA.S52387] [PMID: 25214796]
[28]
Hennigan, S.; Kavanaugh, A. Interleukin-6 inhibitors in the treatment of rheumatoid arthritis. Ther. Clin. Risk Manag., 2008, 4(4), 767-775.
[PMID: 19209259]
[29]
Meng, D.; Liang, L.; Guo, X. Serum interleukin-10 level in patients with inflammatory bowel disease: A meta-analysis. Eur. J. Inflamm., 2019, 17, 205873921984340.
[http://dx.doi.org/10.1177/2058739219843405]
[30]
Vugmeyster, Y.; Szklut, P.; Tchistiakova, L.; Abraham, W.; Kasaian, M.; Xu, X. Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of humanized monoclonal anti-IL-13 antibodies with different IL-13 neutralization mechanisms. Int. Immunopharmacol., 2008, 8(3), 477-483.
[http://dx.doi.org/10.1016/j.intimp.2007.12.004] [PMID: 18279802]
[31]
Cardoso, F.S.; Marcelino, P.; Bagulho, L.; Karvellas, C.J. Acute liver failure: An up-to-date approach. J. Crit. Care, 2017, 39, 25-30.
[http://dx.doi.org/10.1016/j.jcrc.2017.01.003] [PMID: 28131021]
[32]
Rajaram, P.; Subramanian, R. Acute Liver Failure. Semin. Respir. Crit. Care Med., 2018, 39(5), 513-522.
[http://dx.doi.org/10.1055/s-0038-1673372] [PMID: 30485882]
[33]
Rolando, N.; Wade, J.; Davalos, M.; Wendon, J.; Philpott-Howard, J.; Williams, R. The systemic inflammatory response syndrome in acute liver failure. Hepatology, 2000, 32(4 Pt 1), 734-739.
[http://dx.doi.org/10.1053/jhep.2000.17687] [PMID: 11003617]
[34]
Dunn, E.; Sims, J.E.; Nicklin, M.J.H.; O’Neill, L.A.J. Annotating genes with potential roles in the immune system: six new members of the IL-1 family. Trends Immunol., 2001, 22(10), 533-536.
[http://dx.doi.org/10.1016/S1471-4906(01)02034-8] [PMID: 11574261]
[35]
Lamkanfi, M.; Dixit, V.M. Mechanisms and functions of inflammasomes. Cell, 2014, 157(5), 1013-1022.
[http://dx.doi.org/10.1016/j.cell.2014.04.007] [PMID: 24855941]
[36]
Tanaka, T.; Narazaki, M.; Kishimoto, T. Interleukin (IL-6) Immunotherapy. Cold Spring Harb. Perspect. Biol., 2018, 10(8), a028456.
[http://dx.doi.org/10.1101/cshperspect.a028456] [PMID: 28778870]
[37]
Schmidt-Arras, D.; Rose-John, S. IL-6 pathway in the liver: From physiopathology to therapy. J. Hepatol., 2016, 64(6), 1403-1415.
[http://dx.doi.org/10.1016/j.jhep.2016.02.004] [PMID: 26867490]
[38]
Li, L.; Chen, L.; Lin, F.; Mu, J.; Wang, D.; Zhang, W.; Mi, L.; Qin, Y.; Zhou, Y. Study of the expression of inflammatory factors IL-4, IL-6, IL-10, and IL-17 in liver failure complicated by coagulation dysfunction and sepsis. J. Inflamm. Res., 2021, 14, 1447-1453.
[http://dx.doi.org/10.2147/JIR.S302975] [PMID: 33883921]
[39]
Wang, N.; Wang, J.; Jiang, R. Effects of IL-10 on OX62, MHC-II and CD86 in bone marrow DCs in rats with organophosphate poisoning. Exp. Ther. Med., 2018, 15(2), 1906-1909.
[PMID: 29434782]
[40]
McGeachy, M.J.; Cua, D.J.; Gaffen, S.L. The IL-17 family of cytokines in health and disease. Immunity, 2019, 50(4), 892-906.
[http://dx.doi.org/10.1016/j.immuni.2019.03.021] [PMID: 30995505]
[41]
Mathurin, P.; Hadengue, A.; Bataller, R.; Addolorato, G.; Burra, P.; Burt, A. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL clinical practice guidelines: management of alcohol-related liver disease. J. Hepatol., 2018, 69(1), 154-181.
[http://dx.doi.org/10.1016/j.jhep.2018.03.018] [PMID: 29628280]
[42]
Osna, N.A.; Donohue, T.M., Jr; Kharbanda, K.K. Alcoholic liver disease: pathogenesis and current management. Alcohol Res., 2017, 38(2), 147-161.
[PMID: 28988570]
[43]
Elamin, E.E.; Masclee, A.A.; Dekker, J.; Jonkers, D.M. Ethanol metabolism and its effects on the intestinal epithelial barrier. Nutr. Rev., 2013, 71(7), 483-499.
[http://dx.doi.org/10.1111/nure.12027] [PMID: 23815146]
[44]
Szabo, G.; Mandrekar, P.; Petrasek, J.; Catalano, D. The unfolding web of innate immune dysregulation in alcoholic liver injury. Alcohol. Clin. Exp. Res., 2011, 35(5), 782-786.
[http://dx.doi.org/10.1111/j.1530-0277.2010.01398.x] [PMID: 21284666]
[45]
Hill, D.B.; Marsano, L.; Cohen, D.; Allen, J.; Shedlofsky, S.; McClain, C.J. Increased plasma interleukin-6 concentrations in alcoholic hepatitis. J. Lab. Clin. Med., 1992, 119(5), 547-552.
[PMID: 1583411]
[46]
Horiguchi, N.; Wang, L.; Mukhopadhyay, P.; Park, O.; Jeong, W.I.; Lafdil, F.; Osei-Hyiaman, D.; Moh, A.; Fu, X.Y.; Pacher, P.; Kunos, G.; Gao, B. Cell type-dependent pro- and anti-inflammatory role of signal transducer and activator of transcription 3 in alcoholic liver injury. Gastroenterology, 2008, 134(4), 1148-1158.
[http://dx.doi.org/10.1053/j.gastro.2008.01.016] [PMID: 18395093]
[47]
El-Assal, O.; Hong, F.; Kim, W.H.; Radaeva, S.; Gao, B. IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver. Cell. Mol. Immunol., 2004, 1(3), 205-211.
[PMID: 16219169]
[48]
Xing, W.W.; Zou, M.J.; Liu, S.; Xu, T.; Wang, J.X.; Xu, D.G. Interleukin-22 protects against acute alcohol-induced hepatotoxicity in mice. Biosci. Biotechnol. Biochem., 2011, 75(7), 1290-1294.
[http://dx.doi.org/10.1271/bbb.110061] [PMID: 21737938]
[49]
Miller, A.M.; Horiguchi, N.; Jeong, W.I.; Radaeva, S.; Gao, B. Molecular mechanisms of alcoholic liver disease: innate immunity and cytokines. Alcohol. Clin. Exp. Res., 2011, 35(5), 787-793.
[http://dx.doi.org/10.1111/j.1530-0277.2010.01399.x] [PMID: 21284667]
[50]
Grabherr, F.; Grander, C.; Adolph, T.E.; Wieser, V.; Mayr, L.; Enrich, B.; Macheiner, S.; Sangineto, M.; Reiter, A.; Viveiros, A.; Zoller, H.; Bufler, P.; Moschen, A.R.; Dinarello, C.A.; Tilg, H. Ethanol-mediated suppression of IL-37 licenses alcoholic liver disease. Liver Int., 2018, 38(6), 1095-1101.
[http://dx.doi.org/10.1111/liv.13642] [PMID: 29193575]
[51]
Ahmadabadi, B.N.; Hassanshahi, G.; Arababadi, M.K.; Leanza, C.; Kennedy, D. The IL-10 promoter polymorphism at position -592 is correlated with susceptibility to occult HBV infection. Inflammation, 2012, 35(3), 818-821.
[http://dx.doi.org/10.1007/s10753-011-9381-x] [PMID: 21901441]
[52]
Luo, M.X.M.; Wong, S.H.; Chan, M.T.V.; Yu, L.; Yu, S.S.B.; Wu, F.; Xiao, Z.; Wang, X.; Zhang, L.; Cheng, A.S.; Ng, S.S.; Chan, F.K.; Cho, C.H.; Yu, J.; Sung, J.J.; Wu, W.K. Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes. J. Cell. Physiol., 2015, 230(10), 2382-2389.
[http://dx.doi.org/10.1002/jcp.24967] [PMID: 25708728]
[53]
Lan, T.; Chang, L.; Wu, L.; Yuan, Y.F. Il-6 plays a crucial role in hbv infection. J. Clin. Transl. Hepatol., 2015, 3(4), 271-276.
[http://dx.doi.org/10.14218/JCTH.2015.00024] [PMID: 26807383]
[54]
Cavanaugh, V.J.; Guidotti, L.G.; Chisari, F.V. Interleukin-12 inhibits hepatitis B virus replication in transgenic mice. J. Virol., 1997, 71(4), 3236-3243.
[http://dx.doi.org/10.1128/jvi.71.4.3236-3243.1997] [PMID: 9060687]
[55]
Cobleigh, M.A.; Robek, M.D. Protective and pathological properties of IL-22 in liver disease: implications for viral hepatitis. Am. J. Pathol., 2013, 182(1), 21-28.
[http://dx.doi.org/10.1016/j.ajpath.2012.08.043] [PMID: 23159948]
[56]
Zhang, Y.; Cobleigh, M.A.; Lian, J.Q.; Huang, C.X.; Booth, C.J.; Bai, X.F.; Robek, M.D. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology, 2011, 141(5), 1897-1906.
[http://dx.doi.org/10.1053/j.gastro.2011.06.051] [PMID: 21708106]
[57]
Cheng, S.T.; Tang, H.; Ren, J.H.; Chen, X.; Huang, A.L.; Chen, J. Interleukin-34 inhibits hepatitis B virus replication in vitro and in vivo. PLoS One, 2017, 12(6), e0179605.
[http://dx.doi.org/10.1371/journal.pone.0179605] [PMID: 28614380]
[58]
Yang, L.; Zhang, Q.; Song, J.; Wang, W.; Jin, Z. Interleukin-35 suppresses CD8+ T cell activity in patients with viral hepatitis-induced acute-on-chronic liver failure. Dig. Dis. Sci., 2020, 65(12), 3614-3623.
[http://dx.doi.org/10.1007/s10620-020-06077-w] [PMID: 31974915]
[59]
Hu, S.; Lian, P.P.; Hu, Y.; Zhu, X.Y.; Jiang, S.W.; Ma, Q.; Li, L.Y.; Yang, J.F.; Yang, L.; Guo, H.Y.; Zhou, H.; Yang, C.C.; Meng, X.M.; Li, J.; Li, H.W.; Xu, T.; Zhou, H. The Role of IL-35 in the pathophysiological processes of kiver disease. Front. Pharmacol., 2021, 11, 569575.
[http://dx.doi.org/10.3389/fphar.2020.569575] [PMID: 33584256]
[60]
Chalasani, N.; Younossi, Z.; Lavine, J.E.; Charlton, M.; Cusi, K.; Rinella, M.; Harrison, S.A.; Brunt, E.M.; Sanyal, A.J. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the american association for the study of liver diseases. Hepatology, 2018, 67(1), 328-357.
[http://dx.doi.org/10.1002/hep.29367] [PMID: 28714183]
[61]
Tilg, H.; Moschen, A.R. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology, 2010, 52(5), 1836-1846.
[http://dx.doi.org/10.1002/hep.24001] [PMID: 21038418]
[62]
Takaki, A.; Kawai, D.; Yamamoto, K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int. J. Mol. Sci., 2013, 14(10), 20704-20728.
[http://dx.doi.org/10.3390/ijms141020704] [PMID: 24132155]
[63]
Sies, H. Oxidative stress: from basic research to clinical application. Am. J. Med., 1991, 91(3C), 31S-38S.
[http://dx.doi.org/10.1016/0002-9343(91)90281-2] [PMID: 1928209]
[64]
Mokhtari, Z.; Gibson, D.L.; Hekmatdoost, A. Nonalcoholic fatty liver disease, the gut microbiome, and diet. Adv. Nutr., 2017, 8(2), 240-252.
[http://dx.doi.org/10.3945/an.116.013151] [PMID: 28298269]
[65]
Harley, I.T.W.; Stankiewicz, T.E.; Giles, D.A.; Softic, S.; Flick, L.M.; Cappelletti, M.; Sheridan, R.; Xanthakos, S.A.; Steinbrecher, K.A.; Sartor, R.B.; Kohli, R.; Karp, C.L.; Divanovic, S. IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology, 2014, 59(5), 1830-1839.
[http://dx.doi.org/10.1002/hep.26746] [PMID: 24115079]
[66]
Kishimoto, T. IL-6: from its discovery to clinical applications. Int. Immunol., 2010, 22(5), 347-352.
[http://dx.doi.org/10.1093/intimm/dxq030] [PMID: 20410258]
[67]
den Boer, M.A.M.; Voshol, P.J.; Schröder-van der Elst, J.P.; Korsheninnikova, E.; Ouwens, D.M.; Kuipers, F.; Havekes, L.M.; Romijn, J.A. Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice. Endocrinology, 2006, 147(10), 4553-4558.
[http://dx.doi.org/10.1210/en.2006-0417] [PMID: 16709607]
[68]
Yang, L.; Zhang, Y.; Wang, L.; Fan, F.; Zhu, L.; Li, Z.; Ruan, X.; Huang, H.; Wang, Z.; Huang, Z.; Huang, Y.; Yan, X.; Chen, Y. Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22. J. Hepatol., 2010, 53(2), 339-347.
[http://dx.doi.org/10.1016/j.jhep.2010.03.004] [PMID: 20452699]
[69]
Weiskirchen, R.; Tacke, F. Liver fibrosis: from pathogenesis to novel therapies. Dig. Dis., 2016, 34(4), 410-422.
[http://dx.doi.org/10.1159/000444556] [PMID: 27170396]
[70]
van Dijk, F.; Olinga, P.; Poelstra, K.; Beljaars, L. Targeted therapies in liver fibrosis: Combining the best parts of platelet-derived growth factor BB and interferon gamma. Front. Med. (Lausanne), 2015, 2, 72.
[http://dx.doi.org/10.3389/fmed.2015.00072] [PMID: 26501061]
[71]
Puche, J.E.; Saiman, Y.; Friedman, S.L. Hepatic stellate cells and liver fibrosis. Compr. Physiol., 2013, 3(4), 1473-1492.
[http://dx.doi.org/10.1002/cphy.c120035] [PMID: 24265236]
[72]
Gieling, R.G.; Wallace, K.; Han, Y.P. Interleukin-1 participates in the progression from liver injury to fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 296(6), G1324-G1331.
[http://dx.doi.org/10.1152/ajpgi.90564.2008] [PMID: 19342509]
[73]
Lu, D.H.; Guo, X.Y.; Qin, S.Y.; Luo, W.; Huang, X.L.; Chen, M.; Wang, J.X.; Ma, S.J.; Yang, X.W.; Jiang, H.X. Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines. World J. Gastroenterol., 2015, 21(5), 1531-1545.
[http://dx.doi.org/10.3748/wjg.v21.i5.1531] [PMID: 25663772]
[74]
Sonnenberg, G.F.; Nair, M.G.; Kirn, T.J.; Zaph, C.; Fouser, L.A.; Artis, D. Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. J. Exp. Med., 2010, 207(6), 1293-1305.
[http://dx.doi.org/10.1084/jem.20092054] [PMID: 20498020]
[75]
Shi, M.; Wei, J.; Dong, J.; Meng, W.; Ma, J.; Wang, T.; Wang, N.; Wang, Y. Function of interleukin-17 and -35 in the blood of patients with hepatitis B-related liver cirrhosis. Mol. Med. Rep., 2015, 11(1), 121-126.
[http://dx.doi.org/10.3892/mmr.2014.2681] [PMID: 25323532]
[76]
Wang, H.H.; Huang, J.H.; Sue, M.H.; Ho, W.C.; Hsu, Y.H.; Chang, K.C.; Chang, M.S. Interleukin-24 protects against liver injury in mouse models. EBio. Med., 2021, 64, 103213.
[http://dx.doi.org/10.1016/j.ebiom.2021.103213] [PMID: 33508745]
[77]
Mountford, S.; Effenberger, M.; Noll-Puchta, H.; Griessmair, L.; Ringleb, A.; Haas, S.; Denk, G.; Reiter, F.P.; Mayr, D.; Dinarello, C.A.; Tilg, H.; Bufler, P. Modulation of liver inflammation and fibrosis by interleukin-37. Front. Immunol., 2021, 12, 603649.
[http://dx.doi.org/10.3389/fimmu.2021.603649] [PMID: 33746950]
[78]
Hwang, S.; He, Y.; Xiang, X.; Seo, W.; Kim, S.J.; Ma, J.; Ren, T.; Park, S.H.; Zhou, Z.; Feng, D.; Kunos, G.; Gao, B. Interleukin-22 ameliorates neutrophil-driven nonalcoholic steatohepatitis through multiple targets. Hepatology, 2020, 72(2), 412-429.
[http://dx.doi.org/10.1002/hep.31031] [PMID: 31705800]
[79]
Hsia, C.Y.; Huo, T.I.; Chiang, S.Y.; Lu, M.F.; Sun, C.L.; Wu, J.C.; Lee, P.C.; Chi, C.W.; Lui, W.Y.; Lee, S.D. Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma. Eur. J. Surg. Oncol., 2007, 33(2), 208-212.
[http://dx.doi.org/10.1016/j.ejso.2006.10.036] [PMID: 17140760]
[80]
Dudakov, J.A.; Hanash, A.M.; van den Brink, M.R.M. Interleukin-22: immunobiology and pathology. Annu. Rev. Immunol., 2015, 33, 747-785.
[http://dx.doi.org/10.1146/annurev-immunol-032414-112123] [PMID: 25706098]
[81]
Waidmann, O.; Kronenberger, B.; Scheiermann, P.; Köberle, V.; Mühl, H.; Piiper, A. Interleukin-22 serum levels are a negative prognostic indicator in patients with hepatocellular carcinoma. Hepatology, 2014, 59(3), 1207.
[http://dx.doi.org/10.1002/hep.26528] [PMID: 23729376]
[82]
Roth, G.A.; Zimmermann, M.; Lubsczyk, B.A.; Pilz, J.; Faybik, P.; Hetz, H.; Hacker, S.; Mangold, A.; Bacher, A.; Krenn, C.G.; Ankersmit, H.J. Up-regulation of interleukin 33 and soluble ST2 serum levels in liver failure. J. Surg. Res., 2010, 163(2), e79-e83.
[http://dx.doi.org/10.1016/j.jss.2010.04.004] [PMID: 20638676]
[83]
Jin, Z.; Lei, L.; Lin, D.; Liu, Y.; Song, Y.; Gong, H.; Zhu, Y.; Mei, Y.; Hu, B.; Wu, Y.; Zhang, G.; Liu, H. IL-33 released in the liver inhibits tumor growth via promotion of cd4+ and cd8+ t cell responses in hepatocellular carcinoma. J. Immunol., 2018, 201(12), 3770-3779.
[http://dx.doi.org/10.4049/jimmunol.1800627] [PMID: 30446569]
[84]
Tsai, C.L.; Chang, J.S.; Yu, M.C.; Lee, C.H.; Chen, T.C.; Chuang, W.Y.; Kuo, W.L.; Lin, C.C.; Lin, S.M.; Hsieh, S.Y. Functional genomics identifies hepatitis-induced STAT3-TyrO3-STAT3 signaling as a potential therapeutic target of hepatoma. Clin. Cancer Res., 2020, 26(5), 1185-1197.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-3531] [PMID: 31831556]
[85]
Yeh, S.H.; Chen, P.J. Gender disparity of hepatocellular carcinoma: the roles of sex hormones. Oncology, 2010, 78(Suppl. 1), 172-179.
[http://dx.doi.org/10.1159/000315247] [PMID: 20616601]
[86]
Kovalovich, K.; DeAngelis, R.A.; Li, W.; Furth, E.E.; Ciliberto, G.; Taub, R. Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice. Hepatology, 2000, 31(1), 149-159.
[http://dx.doi.org/10.1002/hep.510310123] [PMID: 10613740]
[87]
Louis, H.; Van Laethem, J.L.; Wu, W.; Quertinmont, E.; Degraef, C.; Van den Berg, K.; Demols, A.; Goldman, M.; Le Moine, O.; Geerts, A.; Devière, J. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Hepatology, 1998, 28(6), 1607-1615.
[http://dx.doi.org/10.1002/hep.510280621] [PMID: 9828225]
[88]
Tang, Y.; Bian, Z.; Zhao, L.; Liu, Y.; Liang, S.; Wang, Q.; Han, X.; Peng, Y.; Chen, X.; Shen, L.; Qiu, D.; Li, Z.; Ma, X. Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease. Clin. Exp. Immunol., 2011, 166(2), 281-290.
[http://dx.doi.org/10.1111/j.1365-2249.2011.04471.x] [PMID: 21985374]
[89]
Meng, F.; Wang, K.; Aoyama, T.; Grivennikov, S.I.; Paik, Y.; Scholten, D.; Cong, M.; Iwaisako, K.; Liu, X.; Zhang, M.; Österreicher, C.H.; Stickel, F.; Ley, K.; Brenner, D.A.; Kisseleva, T. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology, 2012, 143(3), 765-776.e3.
[http://dx.doi.org/10.1053/j.gastro.2012.05.049] [PMID: 22687286]
[90]
Kong, X.; Feng, D.; Wang, H.; Hong, F.; Bertola, A.; Wang, F.S.; Gao, B. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice. Hepatology, 2012, 56(3), 1150-1159.
[http://dx.doi.org/10.1002/hep.25744] [PMID: 22473749]
[91]
Jiang, R.; Tan, Z.; Deng, L.; Chen, Y.; Xia, Y.; Gao, Y.; Wang, X.; Sun, B. Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3. Hepatology, 2011, 54(3), 900-909.
[http://dx.doi.org/10.1002/hep.24486] [PMID: 21674558]
[92]
Marvie, P.; Lisbonne, M.; L’helgoualc’h, A.; Rauch, M.; Turlin, B.; Preisser, L.; Bourd-Boittin, K.; Théret, N.; Gascan, H.; Piquet-Pellorce, C.; Samson, M. Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J. Cell. Mol. Med., 2010, 14(6B), 1726-1739.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00801.x] [PMID: 19508382]
[93]
Genetic polymorphisms of interleukin-1B and TNF-A and HBV-Related Hepatocellular Carcinoma. ClinicalTrials.gov., 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT00629486 (Accessed June 2021).
[94]
IL-1 Signal Inhibition in Alcoholic Hepatitis. ClinicalTrials.gov, 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT03775109 (Accessed October 2021).
[95]
Combination Therapy with Interferon Plus Interleukin 2 and Hepatitis B Vaccine in Chronic Hepatitis B Patients. ClinicalTrials.gov., 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT02360592 (Accessed 24 June 2021).
[96]
Efficacy of Low Dose, SubQ Interleukin-2 (IL-2) to Expand Endogenous Regulatory T-Cells in Liver Transplant Recipients. ClinicalTrials.gov., 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT02739412 (Accessed October 2021).
[97]
Doxorubicin and Interleukin-2 in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery. ClinicalTrials.gov., 2011. Available from: https://clinicaltrials.gov/ct2/show/NCT00004248 (Accessed October 2021).
[98]
Levels of Interleukin-6 andTransforming Growth Factor Beta in HCV Patients Sera. ClinicalTrials.gov., 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT03882307 (Accessed October 2021).
[99]
Dose Escalation Study of Interleukin-7 (IL-7) and Bitherapy in HCV Genotype 1 or 4 Patients Resistant to Bitherapy Alone. ClinicalTrials.gov., 2012. Available from: https://clinicaltrials.gov/ct2/show/NCT01025297 (Accessed October 2021).
[100]
Interleukin 12 and Trastuzumab in Treating Patients with Cancer That Has High Level Of HER2/Neu. ClinicalTrials.gov., 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT00004074 (Accessed 24 June 2021).
[101]
A Study of Secukinumab Treatment in Patients With Plaque Psoriasis and Coexisting Non-Alcoholic Fatty Liver Disease (NAFLD). ClinicalTrials.gov., 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04237116 (Accessed 24 June 2021).
[102]
Outcomes in Hepatitis C After Living Donor Liver Transplantation in Association With Interleukin 28B. ClinicalTrials.gov., 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT01429155 (Accessed October 2021).
[103]
ClinicalTrials.gov. A Study on the Correlation Between Interleukin 28B Genotypes With Clinical and Demographic Characteristics in Treatment-Naïve and Treatment-Experienced Patients With Chronic Hepatitis C. ClinicalTrials.gov., 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT01675427 (Accessed October 2021).
[104]
ClinicalTrials.gov. A Study Evaluating IL28B Polymorphism in Patients With HBeAg-Negative Chronic Hepatitis B Treated With Pegasys (Peginterferon Alfa-2a). ClinicalTrials.gov., 2017. Available from: https://clinicaltrials.gov/ct2/show/NCT01697501 (Accessed October 2021).
[105]
IL-35+Breg/IL-35 Effect on T cell Immune in Patients with CHB. ClinicalTrials.gov., 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT03734783 (Accessed 24 June 2021).

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy