Interleukin-4 inhibits growth of multiple myelomas by suppressing interleukin-6 expression

Unfractionated bone marrow (BM) cells obtained from patients with multiple myeloma (MM) exhibit high levels of interleukin (IL)-6. Secretion of IL-6 by these cells as well as spontaneous plasma cell proliferation can be abrogated by neutralizing anti-IL-6 monoclonal antibody (MoAb). Treatment of BM cells with recombinant human (rh)IL-4 at doses of 50 to 250 U/mL blocked endogenous IL-6 synthesis in a dose- dependent fashion and was associated with significant reduction of plasma cell growth that could be reversed by exogenous rhIL-6. Enrichment of BM cells from MM patients for plasma cells and adherent cells and analysis of IL-6 mRNA in these subpopulations by means of quantitative polymerase chain reaction (PCR) showed that adherent BM cells accounted for most of the synthesis of IL-6 transcripts, whereas plasma cells displayed negligible levels of IL-6 mRNA only. These results suggest therapeutic evaluation of rhIL-4 in patients with plasma cell neoplasms.