多発性骨髄腫とIL-6

抄録

Myeloma cells produce IL-6 constitutively, and express its receptor on their surfaces. In vitro, exogenously added IL-6 promotes the growth of myeloma cells from about half of the patients. Therefore, IL-6 is considered as an autocrine growth factor for some myeloma cells. Plasma cells obtained from bone marrow aspirates of benign monoclonal gammopathy (BMG) cases produced IL-6 transiently only after IL-1 stimulation, but not constitutively. Therefore, constitutive production of IL-6 is considered to be characteristic of transformed plasma cells and involved in pathogenesis of multiple myeloma. In two cases with cytokine producig tumors, IL-6 producing renal cell carcinoma and IL-1 producing lung cancer, we could confirm the biological activities of IL-1 and IL-6 on myeloma cells and plasma cells in vivo. To understand the mechanism of the constitutive expression of IL-6 gene in myeloma cells, first, we performed Southern blotting analysis, but we found no gross structural abnormality of the IL-6 gene in myeloma cells. Second, we studied NF-IL6 mRNA expression in myeloma cells by RT-PCR method; NF-IL6 is a nuclear factor that specifically bind the promoter region of the IL-6 gene and activate its transcription. NF-IL6 mRNA expression was detected in a human myeloma cell line, KMS-5 and freshly isolated myeloma cells. Therefore, NF-IL6 may be involved in constitutive IL-6 production in myeloma cells.