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.
|Number of pages||11|
|Journal||Journal of Immunology|
|Publication status||Published - 1 Aug 1997|