Palumbo A, Battaglio S, Napoli P, Omedè P, Fusaro A, Bruno B, Boccadoro M, Pileri A
Dipartimento di Medicina e Oncologia Sperimentale, Ospedale Molinette, Torino, Italy.
Br J Haematol. 1994 Apr;86(4):726-32. doi: 10.1111/j.1365-2141.1994.tb04821.x.
Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and dexamethasone (DEX) have shown anti-tumour effects in multiple myeloma (MM) cells. Bone marrow plasma cells from 39 MM patients were cultured to clarify the intensity and specific activity of each compound on bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion. BrdUrd uptake was inhibited by recombinant human IFN-gamma (100 U/ml) and by DEX (10(-6) M). The stimulation index (StI), i.e. labelling index (LI) of treated samples/controls, was 0.49 +/- 0.09 (mean +/- standard error of the mean, M +/- SEM), P = 0.0003, and 0.52 +/- 0.07 (M +/- SEM), P < 0.0001, respectively. Ig secretion was reduced by IFN-alpha (100 U/ml) and DEX. The secretion index (SI), i.e. Ig quantitation of treated samples/controls, was 0.04 (M +/- SEM), P < 0.0001, and 0.52 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. Finally, IFN-gamma inhibits BrdUrd uptake only and IFN-alpha secretion only. In 18 patients the simultaneous addition of IFN-alpha plus IFN-gamma mainly parallel the effect of IFN-gamma on BrdUrd uptake and IFN-alpha on secretion, but not result in any additive or synergistic effect, though both BrdUrd uptake and Ig secretion were decreased to about the same extent as with DEX. These data indicate that the combination of IFN-alpha plus IFN-gamma and DEX are the strongest inhibitors of both BrdUrd uptake and secretion. Since IFN-alpha and IFN-gamma appear to have a different mechanism of action, their combined use could be considered as a possible new treatment strategy.
α干扰素（IFN-α）、γ干扰素（IFN-γ）和地塞米松（DEX）在多发性骨髓瘤（MM）细胞中已显示出抗肿瘤作用。培养了39例MM患者的骨髓浆细胞，以阐明每种化合物对溴脱氧尿苷（BrdUrd）摄取和免疫球蛋白（Ig）分泌的强度和比活性。重组人IFN-γ（100 U/ml）和DEX（10⁻⁶ M）可抑制BrdUrd摄取。刺激指数（StI），即处理样本的标记指数（LI）/对照，分别为0.49±0.09（平均值±平均标准误差，M±SEM），P = 0.0003，和0.52±0.07（M±SEM），P < 0.0001。IFN-α（100 U/ml）和DEX可减少Ig分泌。分泌指数（SI），即处理样本的Ig定量/对照，分别为0.04（M±SEM），P < 0.0001，和0.52±0.04（M±SEM），P < 0.0001。最后，IFN-γ仅抑制BrdUrd摄取，IFN-α仅抑制分泌。在18例患者中，同时添加IFN-α加IFN-γ主要与IFN-γ对BrdUrd摄取和IFN-α对分泌的作用相似，但未产生任何相加或协同作用，尽管BrdUrd摄取和Ig分泌均降低至与DEX大致相同的程度。这些数据表明，IFN-α加IFN-γ与DEX的组合是BrdUrd摄取和分泌的最强抑制剂。由于IFN-α和IFN-γ似乎具有不同的作用机制，它们的联合使用可被视为一种可能的新治疗策略。
