V alpha 14 natural killer T(V alpha 14 NKT) cells activated by alpha-galactosylceramide (of.-GalCer) secrete a large amount of Th1 and Th2 cytokines. IFN-gamma plays a crucial role in the inflammation response, and is also known as ail activator of nitric oxide (NO) production. We previously reported that lipopolysaccharide (LPS)-induced NO production is augmented by alpha-GalCer in mouse peritoneal cells. Since the liver is susceptible to LPS stimulation via the portal vein, we examined the effect of alpha-GalCer on LPS-induced NO production in murine intra-hepatic lymphocytes (IHLs). Although IHLs augmented LPS-induced NO production by alpha-GalCer administration, Such an augmentation was not observed in non-treated mice. Furthermore, alpha-GalCer did not augment LPS-induced NO production in IHLs from IFN-gamma knockout mice. In flow cytometry analysis of IHLs from alpha-GalCer-treated mice, the ratio and number of F4/80- and TLR4-positive cells rose as compared with non-treated mice. The liver injury may be induced by LPS and NO under the condition where V alpha 14 NKT cells were activated. (C) 2008 Elsevier Inc. All rights reserved.