INTERFERON-GAMMA INTERRUPTS AUTOCRINE GROWTH MEDIATED BY ENDOGENOUS INTERLEUKIN-6 IN RENAL-CELL CARCINOMA

Cells of the renal-cell carcinoma line ACHN constitutively produce IL-6, express the IL-6 receptor and use IL-6 in n autocrine fashion to augment their growth. Growth arrest of ACHN cells can be achieved by exposure of cells to neutralizing monoclonal antibody (MAb) to recombinant human (rh) IL-6. Treatment of ACHN cells with rh IFN-gamma also leads to inhibition of Proliferation of these cells in a dose-dependent manner, that can be reversed by exogenous rh IL-6, while IFN-alpha, IL-2, IL-4 and vinblastine or 17-beta-estradiol has no effect on growth (H-3-thymidine uptake) of ACHN cells and IL-6 expression. Studies on the mechanism of action of IFN-gamma revealed that IFN-gamma was acting by inhibiting the autocrine IL-6-mediated loop generated by ACHN.