Granulocyte-colony stimulating factor inhibits TNF[alpha] production in a human hepatoma cell line

The syndrome of cachexia associated with malignant diseases can be in part attributed to the effects of tumour necrosis factor α (TNFα) which itself is produced by a variety of tumour cells. We have recently reported that the human hepatoma cell line HepG2 expresses the TNFα gene and releases biologically active TNFα protein after stimulation with interleukin-1β (IL-1β). Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein necessary for the proliferation and differentiation of neutrophil progenitor cells in the bone marrow. In addition G-CSF has been reported to exert anti-inflammatory effects. In our study we tested the effect of recombinant human G-CSF (rhG-CSF) on TNFα production in HepG2 cells. It could be shown that rhG-CSF (250 U/ml) significantly reduced IL-1β-induced (300 pg/ml) TNFα gene expression after 1-h and 3-h incubation periods (TNFα mRNA concentrations were: 8.8±2.1 amol/µg total RNA after a 1-h incubation with IL-1β versus 3.8±1.3 amol/µg total RNA after a 1-h incubation with IL-1β + rhG-CSF and 13.8±2.2 amol/µg total RNA after a 3-h incubation with IL-1β versus 8.8±2.1 amol/µg total RNA after a 3-h incubation with IL-1β + rhG-CSF). From these data we conclude that rhG-CSF is a potent inhibitor of cytokine-induced TNFα production by tumour cells. Therefore, treatment of patients with malignant diseases with rhG-CSF might represent a useful tool to improve the tumour-associated cachexia.[PUBLICATION ABSTRACT]