These authors contributed equally to this work.
Opposing effects of prednisolone treatment on T/NKT cell- and hepatotoxin-mediated hepatitis in mice
Article first published online: 21 JAN 2014
Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Volume 59, Issue 3, pages 1094–1106, March 2014
How to Cite
Kwon, H.-J., Won, Y.-S., Park, O., Feng, D. and Gao, B. (2014), Opposing effects of prednisolone treatment on T/NKT cell- and hepatotoxin-mediated hepatitis in mice. Hepatology, 59: 1094–1106. doi: 10.1002/hep.26748
Potential conflict of interest: Nothing to report.
Supported by the intramural program of the NIAAA, NIH.
- Issue published online: 25 FEB 2014
- Article first published online: 21 JAN 2014
- Accepted manuscript online: 1 OCT 2013 08:15AM EST
- Manuscript Accepted: 12 SEP 2013
- Manuscript Received: 18 APR 2013
Prednisolone is a corticosteroid that has been used to treat inflammatory liver diseases such as autoimmune hepatitis and alcoholic hepatitis. However, the results have been controversial, and how prednisolone affects liver disease progression remains unknown. In the current study we examined the effect of prednisolone treatment on several models of liver injury, including T/NKT cell hepatitis induced by concanavalin A (ConA) and α-galactosylceramide (α-GalCer), and hepatotoxin-mediated hepatitis induced by carbon tetrachloride (CCl4) and/or ethanol. Prednisolone administration attenuated ConA- and α-GalCer-induced hepatitis and systemic inflammatory responses. Treating mice with prednisolone also suppressed inflammatory responses in a model of hepatotoxin (CCl4)-induced hepatitis, but surprisingly exacerbated liver injury and delayed liver repair. In addition, administration of prednisolone also enhanced acetaminophen-, ethanol-, or ethanol plus CCl4-induced liver injury. Immunohistochemical and flow cytometric analyses demonstrated that prednisolone treatment inhibited hepatic macrophage and neutrophil infiltration in CCl4-induced hepatitis and suppressed their phagocytic activities in vivo and in vitro. Macrophage and/or neutrophil depletion aggravated CCl4-induced liver injury and impeded liver regeneration. Finally, conditional disruption of glucocorticoid receptor in macrophages and neutrophils abolished prednisolone-mediated exacerbation of hepatotoxin-induced liver injury. Conclusion: Prednisolone treatment prevents T/NKT cell hepatitis but exacerbates hepatotoxin-induced liver injury by inhibiting macrophage- and neutrophil-mediated phagocytic and hepatic regenerative functions. These findings may not only increase our understanding of the steroid treatment mechanism but also help us to better manage steroid therapy in liver diseases. (Hepatology 2014;59:1094–1106)