Portier M, Zhang X G, Caron E, Lu Z Y, Bataille R, Klein B
INSERM U291, Immunopathologie des Maladies Tumorales et Autoimmunes, Montpellier, France.
Blood. 1993 Jun 1;81(11):3076-82.
In multiple myeloma, malignant plasma cells from most patients with active disease proliferate spontaneously when cultured for 5 days in vitro. This spontaneous proliferation is related to the endogenous production of interleukin-6 (IL-6), the major myeloma-cell growth factor. A 50% inhibitory dose (100 U/mL) of human recombinant gamma-interferon (hr gamma-IFN) blocked the proliferation of myeloma cells almost completely in all 19 patients analyzed. This inhibition was not caused by suppression of endogenous IL-6 production and was also observed in the presence of an excess of hrIL-6. hr gamma-IFN was also completely inhibitory in four human myeloma cell lines (HMCL) whose growth is totally dependent on the addition of exogenous hrIL-6. This inhibition was associated with a 47% to 73% decrease in membrane IL-6-binding gp80 protein as well as with a 90% decrease in the amount of gp80 mRNA in HMCL. These results are in line with recent reports indicating that gamma-IFN inhibited several IL-6-dependent biologic processes. They suggest a need to reconsider why previous preliminary clinical trials failed to demonstrate a beneficial effect of gamma-IFN in multiple myeloma.
在多发性骨髓瘤中，大多数患有活动性疾病的患者的恶性浆细胞在体外培养5天时会自发增殖。这种自发增殖与白细胞介素-6（IL-6）的内源性产生有关，IL-6是主要的骨髓瘤细胞生长因子。在所有19例分析的患者中，50%抑制剂量（100 U/mL）的人重组γ干扰素（hrγ-IFN）几乎完全阻断了骨髓瘤细胞的增殖。这种抑制不是由内源性IL-6产生的抑制引起的，并且在存在过量hrIL-6的情况下也观察到。hrγ-IFN对四种人骨髓瘤细胞系（HMCL）也具有完全抑制作用，这些细胞系的生长完全依赖于外源性hrIL-6的添加。这种抑制与HMCL中膜IL-6结合gp80蛋白减少47%至73%以及gp80 mRNA量减少90%有关。这些结果与最近的报告一致，表明γ-IFN抑制了几种IL-6依赖性生物学过程。它们表明需要重新考虑为什么以前的初步临床试验未能证明γ-IFN在多发性骨髓瘤中具有有益作用。
