Recombinant interferon-gamma inhibits the growth of IL-6-dependent human multiple myeloma cell lines in vitro.
Recombinant human IFN-gamma (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-gamma. The effect of IFN-gamma 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-gamma was not due to differences in IFN-gamma receptor expression. The growth inhibition was not a consequence of an IFN-gamma-induced terminal differentiation as flow cytometric analyses demonstrated an arrest in all phases of the cell cycle. IFN-alpha 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-gamma sensitivity. Furthermore, the study demonstrates that MM cell lines are not simultaneously sensitive to IFN-gamma and alpha, indicating that the mechanisms of action of the two types of IFN are distinct.
Jernberg-Wiklund
H
H
Department of Pathology, University Hospital, Uppsala, Sweden.
Pettersson
M
M
Nilsson
K
K
D002455:Cell Division; D002470:Cell Survival; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D017471:Receptors, Interferon; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D007371:Interferon-gamma