Figure 1.

Actions of IL-6 in the diseased bone marrow microenvironment. (A) Myeloma cells or other inflammatory triggers can induce osteoclast differentiation and osteolytic activity, which releases growth factors and IL-6 stored in the bone matrix (B). (C) Myeloma cells, or other inflammatory mediators, activate the release of IL-6 from osteoblasts (D); IL-6 then inhibits the activity of osteoblasts and induces their production of RANKL (E). (F,G) IL-6 from many sources, as well as RANKL from osteoblasts, induce pre-osteoclasts to differentiate into mature osteoclasts, which then resorb bone to induce greater release of stored growth factors, creating a vicious cycle. (H) Myeloma cells also alter bone marrow adipocytes to make a more supportive niche for tumor cells and to increase osteoclastic activity through IL-6 and other molecules.