Recombinant interferon- γ inhibits the growth of IL-6-dependent human multiple myeloma cell lines in vitro

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Abstract
Recombinant human IFN‐γ (100–1000 U/ml) inhibited the IL‐6‐induced growth of 2 human IL‐6‐dependent multiple myeloma (MM) cell lines U‐1958 and U‐266–1970 in vitro. In contrast, the U‐1996 line, independent of IL‐6 for maintenance at a slow growth rate but responding to IL‐6 by increased proliferation, and the IL‐6‐independent U‐266–1984 were refractory to the anti‐proliferative effect of IFN‐γ. The effect of IFN‐γ in the sensitive MM cell lines was cytostatic in U‐266–1970, and cytostatic and cytotoxic in U‐1958. Northern blot analysis revealed that the growth inhibition of the IL‐6‐dependent MM cell line U‐1958 was not due to down‐regulation of IL‐6 receptor mRNA expression and that the differential sensitivity to IFN‐γ was not due to differences in IFN‐γ receptor expression. The growth inhibition was not a consequence of an IFN‐γ‐induced terminal differentiation as flow cytometric analyses demonstrated an arrest in all phases of the cell cycle. IFN‐α inhibited the growth in 3 of the 4 cell lines tested. The results thus suggest that the particular MM phenotype, which includes IL‐6 dependency for survival and growth, may also be characterized by IFN‐γ sensitivity. Furthermore, the study demonstrates that MM cell lines are not simultaneously sensitive to IFN‐γ and α, indicating that the mechanisms of action of the two types of IFN are distinct.