Opposing effects of prednisolone treatment on T/NKT cell‐ and hepatotoxin‐mediated hepatitis in mice. Issue 3 (21st January 2014)

• Record Type: Journal Article
• Authors: Kwon, Hyo‐Jung; Won, Young‐Suk; Park, Ogyi; Feng, Dechun; Gao, Bin
• Is Part Of: Hepatology. Volume 59:Issue 3(2014:Mar.)
• Page Start: 1094
• Page End: 1106
• Publication Date: 2014-01-21
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.26748
• Languages: English
• ISSNs: 0270-9139

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 (CCl<sub>4</sub>) 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 (CCl<sub>4</sub>)‐induced hepatitis, but surprisingly exacerbated liver injury and delayed liver repair. In addition, administration of prednisolone also enhanced acetaminophen‐, ethanol‐, or ethanol plus CCl<sub>4</sub>‐induced liver injury. Immunohistochemical and flow cytometric analyses demonstrated that prednisolone treatment inhibited hepatic macrophage and neutrophil infiltration in CCl<sub>4</sub>‐induced hepatitis and suppressed their phagocytic activities <italic>in vivo</italic> and <italic>in vitro</italic>. Macrophage and/or neutrophil depletion aggravated CCl<sub>4</sub>‐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. <italic>Conclusion</italic>: 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. (H<sc>epatology</sc> 2014;59:1094–1106)</p> </abstract>