Restoration of macrophage tumoricidal activity by bleomycin correlates with the decreased production of transforming growth factor β in rats bearing KDH-8 hepatoma cells

Abstract

 To explore the mechanisms of immuno-modulatory activities of bleomycin, we investigated interferon γ (IFNγ) mRNA expression, tumor necrosis factor α (TNFα) production, nitric oxide (NO) production and macrophage tumoricidal activities in rats bearing KDH-8 hepatoma cells, which secreted a large amount of transforming growth factor β (TGFβ), and these processes in KDH-8 tumor-bearing rats treated with bleomycin. We found that IFNγ mRNA expression, TNFα production, NO production and macrophage cytotoxic activities were lower in the KDH-8-bearing rats than in normal rats. On the other hand, low-dose bleomycin restored the macrophage cytotoxic activities, NO production, IFNγ mRNA expression and TNFα production in the KDH-8-bearing rats. In vitro experiments showed that KDH-8-derived TGFβ decreased the IFNγ mRNA expression and TNFα production in splenocytes, and NO production in peritoneal macrophages. These results suggest that low-dose bleomycin restored the cytokine production and macrophage tumoricidal activities in the KDH-8-bearing rats by decreasing KDH-8-derived TGFβ.