Expression of interleukin-1 beta and tumour necrosis factor-alpha in plasma cells from patients with multiple myeloma

Interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) are potent bone resorbing cytokines that may contribute to the development of the osteolytic bone disease observed In patients with multiple myeloma (MM). Although these factors have been identified in cultures of bone marrow mononuclear cells isolated from patients, the identity of the cells responsible for producing IL-1 beta and TNF alpha remains unclear. Using a sensitive dual-colour fluorescence in situ hybridization (PISH) technique and a two-colour immunofluorescence method we have investigated the expression of the mRNA and protein, for IL-1 beta and TNF alpha, by individual bone marrow plasma cells from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The mRNA for IL-1 beta and TNF alpha was identified in all cells expressing the immunoglobulin light chain from all patients with MM and MGUS. However, the IL-1 beta protein could not be detected in cytoplasmic light chain positive cells in any of the patients examined, In contrast, the TNF alpha protein was detected in clonal plasma cells from patients with both MM and MGUS. Interestingly, the IL-1 beta and TNF alpha mRNA and proteins were readily detected within a small proportion of the non-plasma cells from patients with both MM and MGUS. These data suggest that myeloma cells in vivo are able to produce TNF alpha but not IL-1 beta, In addition, a small proportion of accessory cells are likely to be able to contribute to the production of both IL-1 beta and TNF alpha.