Sati H I, Greaves M, Apperley J F, Russell R G, Croucher P I
Division of Biochemical and Musculoskeletal Medicine, University of Sheffield Medical School.
Br J Haematol. 1999 Feb;104(2):350-7. doi: 10.1046/j.1365-2141.1999.01193.x.
Interleukin-1beta(IL-1beta) 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-1beta and TNFalpha remains unclear. Using a sensitive dual-colour fluorescence in situ hybridization (FISH) technique and a two-colour immunofluorescence method we have investigated the expression of the mRNA and protein, for IL-1beta and TNFalpha, by individual bone marrow plasma cells from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The mRNA for IL-1beta and TNFalpha was identified in all cells expressing the immunoglobulin light chain from all patients with MM and MGUS. However, the IL-1beta protein could not be detected in cytoplasmic light chain positive cells in any of the patients examined. In contrast, the TNFalpha protein was detected in clonal plasma cells from patients with both MM and MGUS. Interestingly, the IL-1beta and TNFalpha 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 TNFalpha but not IL-1beta. In addition, a small proportion of accessory cells are likely to be able to contribute to the production of both ILbeta and TNFalpha.
白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）是强效的骨吸收细胞因子，可能与多发性骨髓瘤（MM）患者中观察到的溶骨性骨病的发生有关。尽管在从患者分离的骨髓单核细胞培养物中已鉴定出这些因子，但负责产生IL-1β和TNF-α的细胞身份仍不清楚。我们使用灵敏的双色荧光原位杂交（FISH）技术和双色免疫荧光方法，研究了MM患者和意义未明的单克隆丙种球蛋白病（MGUS）患者的单个骨髓浆细胞中IL-1β和TNF-α的mRNA和蛋白质表达。在所有MM和MGUS患者中，在所有表达免疫球蛋白轻链的细胞中均鉴定出了IL-1β和TNF-α的mRNA。然而，在所检查的任何患者的细胞质轻链阳性细胞中均未检测到IL-1β蛋白。相比之下，在MM和MGUS患者的克隆浆细胞中检测到了TNF-α蛋白。有趣的是，在MM和MGUS患者的一小部分非浆细胞中很容易检测到IL-1β和TNF-α的mRNA和蛋白质。这些数据表明，体内骨髓瘤细胞能够产生TNF-α，但不能产生IL-1β。此外，一小部分辅助细胞可能能够促进IL-1β和TNF-α的产生。
