Involvement of IL-6 in development of myeloma

Myeloma is a hematological disorder of proliferative and accumulative increase in malignant plasma cells. Recent work reveals that interleukin 6 (IL-6) is a major factor in the growth of human myeloma cells, and that myeloma cells constitutively produce IL-6 and express IL-6 receptors. It has been shown that an autocrine loop is operating in freshly isolated myeloma cells. Therefore, a constitutive production of IL-6 and activation of the IL- 6 gene could be involved in the oncogenesis of human myeloma. This hypothesis is supported by two findings: 1) in IL-6 transgenic mice, a massive plasmacytosis was observed in lymph nodes, spleen and thymus. 2) Plasma cells from benign monoclonal gammopathy, premyeloma state, and polyclonal gammopathy could not constitutively produce IL-6. Recent studies also showed that there were no structural alterations of IL-6 genes, but that a positive transcriptional factor for IL-6 gene, NF-IL6, was expressed constitutively in all myeloma cells. It is therefore concluded that the constitutive activation of IL-6 gene could be important in oncogenesis of myeloma, and that this might be induced by altered expression of transcriptional factors but not by structural alteration of the IL-6 gene itself.