Additive/Synergistic Effects of Interleukin-6 and Interleukin-10 on the Proliferation of Human Myeloma Cells

Abstract

Multiple myeloma (MM) is a haematological disorder of malignant plasma cells. Interleukin-6 (IL-6) is a major proliferative factor for the malignant plasma cells. Interleukin-10 (IL-10) is an Interleukin-6 related growth factor for multiple myeloma cells. Aim: (1) to investigate the combination treatment with IL-6 and IL-10 on the proliferation in human myeloma cells, (2) to investigate the uptake of exogenous IL-6 by cultivated myeloma cells. Materials and Methods: Four human multiple myeloma cell lines were investigated in an in vitro model. Parameters: Viability, Cytokine production, Membrane expressions of IL-6 receptor and IL-10 receptor, Cell proliferation. Results: IL-6 increased the production of IL-10 (spontaneous: ND-79, induced up to 939 pg/ml). Both cytokines enhanced the proliferation in all cell lines. The proliferation rate for IL-6 lay between 120-138%, for IL-10 between 116-128%. The combination of 1L-6 with IL-10 led to additive/synergistic effects in the proliferation of myeloma cells. IL-6 increased its receptor up to 192%. The up-regulation of the IL-10 receptor by IL-6 was less (110-129%). After 1 hour of incubation already 62-76 % of exogenous IL-6 was taken into the cells. At 24 hours the uptake of IL-6 was 84-90%. Conclusion: The additive/synergistic effects of IL-6 and IL-10 have an important value in the treatment of multiple myeloma. The key position of the complex IL-6/IL-6R gives reasons for a specific- targeted therapy with new perspectives for the future: When the cytokine1 induces the synthesis of cytokine2 leading to enhanced cell-proliferation then by the inhibition of cytokine1 the effect of cytokine2 also will be abolished.