Suppression of Concanavalin A-Induced Hepatitis in IFN-γ-/- Mice, but Not in TNF-α-/- Mice: Role for IFN-γ in Activating Apoptosis of Hepatocytes

Yoh Ichi Tagawa, Kenji Sekikawa, Yoichiro Iwakura

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359 Citations (Scopus)

Abstract

Con A-induced hepatitis (Con A-hepatitis) is a hepatitis model in which hepatic injury is supposed to be caused by cytokines from activated T cells. To elucidate the pathogenesis of this disease, we analyzed the roles of IFN-γ and TNF-α using deficient mice of these cytokines. Development of hepatitis was reduced significantly in IFN-γ-/- mice, while susceptibility of TNF-α-/- mice was not changed. Interestingly, apoptotic cell death was observed in the affected livers of control or TNF-α-/- mice, but not in those of IFN-γ-/- mice. Fas mRNA expression was increased in the livers of hepatitis mice, but less abundantly in those of IFN-γ-/- mice. Since apoptosis of liver cells was rarely observed in Con A-treated lpr/lpr mice, involvement of the Fas-Fas ligand system in this apoptotic process was suggested. These observations suggest that IFN-γ plays a central role in Con A-hepatitis by activating Fas-induced apoptosis of liver cells.

Original languageEnglish
Pages (from-to)1418-1428
Number of pages11
JournalJournal of Immunology
Volume159
Issue number3
Publication statusPublished - 1 Aug 1997

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