title: Opposing effects of prednisolone treatment on T/NKT cell- and hepatotoxin-mediated hepatitis in mice.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA; College of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon, South Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Won
authors.forename: Ogyi
authors.initials: O
authors.lastname: Park
authors.forename: Dechun
authors.initials: D
authors.lastname: Feng
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003208:Concanavalin A / Q000633:toxicity; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000633:toxicity; D005938:Glucocorticoids / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011239:Prednisolone / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D005699:Galactosylceramides; D005938:Glucocorticoids; D008934:Mitogens; C493154:alpha-galactosylceramide; D003208:Concanavalin A; D011239:Prednisolone; D002251:Carbon Tetrachloride