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J Hepatol. 2005 Oct;43(4):670-8.

Neutralization of tumor necrosis factor abrogates hepatic failure induced by alpha-galactosylceramide without attenuating its antitumor effect in aged mice.

Author information

1
Department of Microbiology, National Defense Medical College, Namiki, Tokorozawa, Japan.

Abstract

BACKGROUND/AIMS:

The functions of mouse liver NK1.1+ T (NKT) cells stimulated with alpha-galactosylceramide (alpha-GalCer) are enhanced age dependently, and the antitumor and anti-metastatic effect in the liver is dependent on IFN-gamma. However, hepatic injury is independent of IFN-gamma and Fas/Fas-ligand dependent. The aim of this study is to investigate how tumor necrosis factor is involved in the alpha-GalCer-mediated immune phenomena.

METHODS:

C57BL/6 mice were intraperitoneally treated with anti-TNF antibody 1 h before alpha-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 alpha-GalCer injection were evaluated. IFN-gamma production and antitumor immunity in the liver after the intravenous injection of EL-4 cells were also assessed.

RESULTS:

Serum TNF levels after alpha-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 alpha-GalCer and thereby reduced the mortality of old mice, whereas it did not affect the IFN-gamma production from NKT cells, the antitumor immunity in the liver nor the mouse survival after EL-4 injection.

CONCLUSIONS:

NKT cells activated by alpha-galactosylceramide participated in either antitumor immunity or hepatic injury using IFN-gamma and TNF/Fas-L, respectively.

PMID:
15922476
DOI:
10.1016/j.jhep.2005.02.027
[Indexed for MEDLINE]

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