Attenuated liver fibrosis and depressed serum albumin levels in carbon tetrachloride-treated IL-6-deficient mice

Abstract

Chronic intermittent injection of carbon tetrachloride (CCl 4 ) for more than 10 weeks induced liver fibrosis in mice, as evidenced by positive Azan staining and increased intrahepatic collagen content. Preceding the onset of liver fibrosis, interleukin-6 (IL-6) gene expression was enhanced in liver and immunoreactive IL-6 was detected in infiltrating inflammatory cells. To delineate the role of IL-6 in this process, we treated IL-6-deficient mice with CCl 4 in a similar manner for 12 weeks, after which fibrotic changes were less evident and serum albumin levels were lower in IL-6-deficient than wild-type mice. Moreover, CCl 4 -induced expression of transforming growth factor ␤ 1 and hepatocyte growth factor genes in liver was significantly reduced in IL-6-deficient mice. Thus, IL-6 may be vitally involved in fibrotic changes and maintenance of serum albumin levels, partly by modulating intrahepatic expression of these cytokines. J. Leukoc. Biol. 66: 601-608; 1999.

Replicative Senescence of Activated Human Hepatic Stellate Cells Is Accompanied by A Pronounced Inflammatory But Less Fibrogenic Phenotype

“…22 Studies in experimental models of liver fibrosis using IL-6 knockout mice produce conflicting results; one group found that fibrosis was reduced in mice lacking IL-6, and another group reported the opposite. 38,39 IL-8 is a potent chemoattractant for neutrophils, and its level is correlated with disease activity in human alcoholic liver fibrosis. 40,41 HSCs further contribute to hepatic inflammation by expressing 2 leukocyte adhesion molecules, ICAM-1 and VCAM-1, thereby enabling adhered leukocytes to migrate from the sinusoid into the liver parenchyma.…”

Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-β1 production

“…Since primary hepatocytes can be isolated in large quantities and have the ability to produce a significant amount of TGF-b1 (Bissell et al, 1995), we used primary hepatocytes first. IL-6 could be involved in the induction of TGF-b1, since the expression of TGFb1 was significantly reduced in IL-6-deficient mice (Natsume et al, 1999). Real-time PCR analysis indicated that the TGF-b1 mRNA levels increased in response to IL-6.…”

Genetic Polymorphisms and the Progression of Liver Fibrosis: A Critical Appraisal

“…Second, gene expression has been studied in rodent models of hepatic fibrosis, 8 including hepatic toxins, bile duct ligation, and alcohol administration. Third, mutations generated by gene targeting in mice have re-vealed key genes that modify experimental hepatic fibrosis [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] (Table 1). And finally, the development of powerful techniques to study gene expression profile ("microarray chips") has facilitated the identification of potential candidate genes that are up-regulated in both activated HSCs and the fibrotic liver.…”