INTERFERON-ALPHA DOWN-REGULATES THE INTERLEUKIN-6 RECEPTOR IN A HUMAN MULTIPLE-MYELOMA CELL-LINE, U266

The effects of interferon-alpha (IFN-alpha) on the interleukin-6 (IL-6) receptor in a multiple myeloma cell line, U266, have been examined. IFN-alpha inhibits [H-3]thymidine incorporation in U266 cells in a time- and dose-dependent manner. Furthermore, IFN-alpha inhibits the ability of IL-6 to induce increases in [H-3]thymidine incorporation. While IFN-alpha suppresses the ability of (l25)IL-6 to bind to the IL-6 receptor on U266 cells, this effect is not due to competition of IFN-alpha with IL-6 for the IL-6 receptor. Although IFN-alpha induces IL-6 synthesis in the U266 cell, inhibition of IL-6 binding occurs when IL-6 synthesis is minimal. Furthermore, after pretreatment of U266 cells with neutralizing anti-IL-6 antibodies, IFN-alpha still inhibits I-125-IL-6 binding. These data suggest that IFN-alpha inhibition of I-125-IL-6 binding does not involve IL-6 synthesis. IFN-alpha reduces I-125-IL-6 binding without affecting its affinity, suggesting that IFN-alpha inhibits IL-6 receptor expression. Although pretreatment with cycloheximide inhibits I-125-IL-6 binding, IFN-alpha does not cause a selective decrease in the levels of gp130 or IL-6 receptor mRNA at times when I-125- IL-6 binding is inhibited. These observations indicate that IFN-alpha-alpha lowers IL-6 receptor density on U266 Cells by mechanisms other than competitive binding or lowering IL-6 receptor mRNA production. Receptor down-regulation may be a mechanism of IFN-alpha-induced inhibition of growth in U266 cells.