» Articles » PMID: 20166853

Suppressive and Pro-inflammatory Roles for IL-4 in the Pathogenesis of Experimental Drug-induced Liver Injury: a Review

Overview
Publisher Informa Healthcare
Date 2010 Feb 20
PMID 20166853
Citations 13
Authors
Affiliations
Soon will be listed here.
Abstract

Importance Of The Field: Idiosyncratic drug reactions resulting in drug-induced liver injury (DILI) account for approximately 13% of acute liver failure cases in the US. Idiosyncratic drug reactions are the third most common cause of liver transplantation, exceeded only by acetaminophen and indeterminate causes. Clinical evidence suggests that idiosyncratic DILI is triggered by drug hapten-altered self proteins resulting in hepatocellular injury. An example of this type of DILI is hepatitis that develops in susceptible individuals following administration of halogenated volatile anesthetics, dihydralazine, carbamazepine or diclofenac.

Areas Covered In This Review: In this review, we describe research in animal models that supports a critical role for suppressive and pro-inflammatory roles for IL-4 in the pathogenesis of immune-mediated DILI.

What The Reader Will Gain: The reader will gain insights into the roles of IL-4 in the development of experimental DILI. The reader will gain tools to assist in the translation of these findings to those in patients with immune-mediated DILI, as well as other inflammatory diseases of the liver. The reader will then be made aware of gaps in knowledge in the pathogenesis of DILI where research could result in significant advances in the care of these complicated patients.

Take Home Message: In experimental immune-mediated DILI, IL-4 suppresses regulatory responses to CYP2E1 autoantigens but induces pro-inflammatory responses to drug haptens.

Citing Articles

Clinical features and prognosis of drug-induced liver injury in patients with non-alcoholic fatty liver.

Zhao Y, Li J, Liu Y, Zhu Y, Zhang Y, Zheng W World J Hepatol. 2025; 17(2):101741.

PMID: 40027577 PMC: 11866136. DOI: 10.4254/wjh.v17.i2.101741.


Anti-inflammatory effect and antihepatoma mechanism of carrimycin.

Li X, Luo Y, Wang Y, Yang Z, Shang Y, Guan Q World J Gastroenterol. 2023; 29(14):2134-2152.

PMID: 37122599 PMC: 10130968. DOI: 10.3748/wjg.v29.i14.2134.


Effects of Casein Phosphopeptide-Selenium Complex on the Immune Functions in Beagle Dogs.

Wang W, Xu L, Cao Y, Liu G, Lin Q, Mao X Animals (Basel). 2022; 12(16).

PMID: 36009627 PMC: 9404450. DOI: 10.3390/ani12162037.


Endometrial regenerative cells with galectin-9 high-expression attenuate experimental autoimmune hepatitis.

Wang H, Zhao Y, Ren B, Qin Y, Li G, Kong D Stem Cell Res Ther. 2021; 12(1):541.

PMID: 34654474 PMC: 8518235. DOI: 10.1186/s13287-021-02604-2.


Naringin and Hesperidin Counteract Diclofenac-Induced Hepatotoxicity in Male Wistar Rats Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.

Hassan R, Hozayen W, Abo Sree H, Al-Muzafar H, Amin K, Ahmed O Oxid Med Cell Longev. 2021; 2021:9990091.

PMID: 34422219 PMC: 8376442. DOI: 10.1155/2021/9990091.


References
1.
Nelms K, Keegan A, Zamorano J, Ryan J, Paul W . The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol. 1999; 17:701-38. DOI: 10.1146/annurev.immunol.17.1.701. View

2.
Neuberger J, Mieli-Vergani G, Tredger J, Davis M, Williams R . Oxidative metabolism of halothane in the production of altered hepatocyte membrane antigens in acute halothane-induced hepatic necrosis. Gut. 1981; 22(8):669-72. PMC: 1420052. DOI: 10.1136/gut.22.8.669. View

3.
Bourdi M, Eiras D, Holt M, Webster M, Reilly T, Welch K . Role of IL-6 in an IL-10 and IL-4 double knockout mouse model uniquely susceptible to acetaminophen-induced liver injury. Chem Res Toxicol. 2007; 20(2):208-16. DOI: 10.1021/tx060228l. View

4.
Schiodt F, Atillasoy E, Shakil A, Schiff E, Caldwell C, Kowdley K . Etiology and outcome for 295 patients with acute liver failure in the United States. Liver Transpl Surg. 1999; 5(1):29-34. DOI: 10.1002/lt.500050102. View

5.
Moscat J, Rennert P, Diaz-Meco M . PKCzeta at the crossroad of NF-kappaB and Jak1/Stat6 signaling pathways. Cell Death Differ. 2005; 13(5):702-11. DOI: 10.1038/sj.cdd.4401823. View