Clinical significance of interleukin-6 gene expression in the bone marrow of patients with multiple myeloma.

The proliferation and differentiation of multiple myeloma (MM) cells has been suggested to be induced by continuous stimulation of interleukin (IL)-6 in the bone marrow (BM) microenvironment. We investigated the production and gene expression of this cytokine in bone marrow mononuclear cells (BMMC) of 31 untreated patients with MM. The IL-6 gene was expressed in 20/31 patients in whom increased IL-6 production in vitro was observed, suggesting that IL-6 gene expression correlates with IL-6 production by BMMC. A significant correlation was found between the presence of bone lesions and IL-6 gene expression; however, the percentage of MM cells infiltrating the BM did not correlate with IL-6 gene expression. This IL-6 gene expression was assigned to adherent cells of the BM microenvironment. Furthermore, serial measurement of IL-6 gene expression along with the clinical course revealed increased expression of IL-6 gene during the progressive phase of MM and decreased expression after remission at the individual level. These results suggest that IL-6 gene expression in BMMC reflects disease severity in MM.