Possible availability of N-acetylcysteine as an adjunct to cytokine therapy for hepatocellular carcinoma.

To examine the possibility of immunotherapy for activating liver-associated mononuclear cells (liver MNC) in hepatocellular carcinoma (HCC), we evaluated the cytotoxicity of liver MNC and peripheral blood mononuclear cells (PBMNC) in HCC patients and examined how they can be activated by cytokines and how this activation is modulated by reduction/oxidation. Cytotoxicity of liver MNC but not PBMNC in HCC patients was significantly decreased compared with that of controls, despite no alteration in the subpopulation of liver MNC between the two groups. We next measured intracellular glutathione (GSH), which is required for the enhancement of the cytotoxicity by interleukin-2 (IL-2). Intracellular GSH levels of liver MNC in HCC were significantly lower than that of controls. In vitro administration of N-acetylcysteine (NAC) not only restored intracellular GSH levels but also enhanced the IL-2-stimulated cytotoxicity of liver MNC in HCC patients. This suggests that intracellular GSH of liver MNC in HCC may participate in the modulation of cytotoxicity of liver MNC in vitro and that NAC may be effective as an adjunct to immunotherapy for HCC.