Multiple myeloma (MM) is a B cell malignancy characterised by the presence of a monoclonal population of terminally differentiated plasma cells in the bone marrow. It generally occurs in older people. Clinical manifestations result from monoclonal protein (immunoglobulin) production and accumulation in the serum and / or the urine, anaemia, lytic bone disease, hypercalcaemia, renal insufficiency and immune deficiency. II-6 is thought to be the major growth factor of MM but the part played by other cytokines in the pathogenesis of the disease is unclear. In the use of cloned U266 cells we hoped to gain an insight into the cytokines that are important in the survival / expansion of the myeloma clone. In this study we demonstrate that these myeloma clones express a variety of cytokine mRNA transcripts, IL-lalpha, IL-ibeta, IL-6, IL-15 and TGF-beta. IL-6, although considered the major proliferative factor, was observed in one clone only. In contrast TGF- beta mRNA transcripts were expressed by many clones. These clones were capable of suppressing T cell responses. However if IL-15 and TGF- beta mRNA transcripts were co-expressed, the suppression of T cell proliferation was more pronounced. Due to these findings, it was decided to further investigate the effects of EL-6 and IL-15 on myeloma clones. Cell studies examining the effects of exogenous IL-6 or IL-15 alone or in combination with dexamethasone on cell cycle, proliferation, apoptosis and cell signalling were performed. The U266 cells were found to be sensitive to the anti-proliferative effect of dexamethasone, while most of the myeloma clones were resistant. IL-6 and IL-15 were able to protect the U266 cells from the effects of dexamethasone at 50mu/ml but not at 100mu/ml. However we observed a significant reduction in proliferation when IL-15 was added in combination with dexamethasone to clone M3 (expresses mRNA transcripts for IL-15, TGF- beta). This clone was resistant to dexamethasone alone. The role of IL-15 is complex and seems to behave differently depending on what other cytokines are present. Further studies may help elucidate the role of IL-15 in the pathogenesis of this disease
