Journal of Hepatology

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Neutralization of tumor necrosis factor abrogates hepatic failure induced by ?-galactosylceramide without attenuating its antitumor effect in aged mice, 3 May 2005
Inui T, Nakashima H, Habu Y, Nakagawa R, Fukasawa M, Kinoshita M, Shinomiya N, Seki S
pages 670-678
Background/Aims
The functions of mouse liver NK1.1+ T (NKT) cells stimulated with ?-galactosylceramide (?-GalCer) are enhanced age dependently, and the antitumor and anti-metastatic effect in the liver is dependent on IFN-?. However, hepatic injury is independent of IFN-? and Fas/Fas-ligand dependent. The aim of this study is to investigate how tumor necrosis factor is involved in the ?-GalCer-mediated immune phenomena.
Methods
C57BL/6 mice were intraperitoneally treated with anti-TNF antibody 1h before ?-GalCer injection, and Fas-ligand expression of NKT cells, the serum ALT levels and histopathological findings of the liver, kidney and lung and mortality after ?-GalCer injection were evaluated. IFN-? production and antitumor immunity in the liver after the intravenous injection of EL-4 cells were also assessed.
Results
Serum TNF levels after ?-GalCer injection increased age dependently in mice. Anti-TNF Ab reduced Fas-ligand (Fas-L) expression of NKT cells while it completely inhibited organ injuries induced by ?-GalCer and thereby reduced the mortality of old mice, whereas it did not affect the IFN-? production from NKT cells, the antitumor immunity in the liver nor the mouse survival after EL-4 injection.
Conclusions
NKT cells activated by ?-galactosylceramide participated in either antitumor immunity or hepatic injury using IFN-? and TNF/Fas-L, respectively.