Lu Z Y, Zhang X G, Rodriguez C, Wijdenes J, Gu Z J, Morel-Fournier B, Harousseau J L, Bataille R, Rossi J F, Klein B
Institute of Molecular Genetics, CNRS BP5051, Montpellier, France.
Blood. 1995 May 1;85(9):2521-7.
Because interleukin-10 (IL-10) is a potent differentiation factor of human B cells into mature plasma cells, we investigated its effect on human malignant plasma cells. IL-10 did not induce any differentiation and increase in Ig synthesis in four human IL-6-dependent malignant plasma cell lines. However, it stimulated the proliferation of two of four cytokine-dependent cell lines in the absence of IL-6 and IL-10-dependent myeloma cell lines have been obtained. The myeloma cell growth activity of IL-10 was unaffected by anti-IL-6 and anti-IL-6R antibodies. Similarly, IL-10 stimulated (P = .001) the proliferation of freshly-explanted myeloma cells in IL-6-deprived cultures of tumor samples from patients with active multiple myeloma (MM) and produced twice as many myeloma cells in these cultures. Again, this cytokine was unable to induce further differentiation (assessed by rate of Ig production) of fresh myeloma cells. A very sensitive enzyme-linked immunosorbent assay (ELISA; 1 pg/mL) only rarely detected IL-10 in the sera of MM patients (3 of 89). On the contrary, serum IL-10 was detected in 60% of patients with plasma cell leukemia (12 of 20). These data show that IL-10 is an IL-6-unrelated growth factor for malignant plasmablastic cells. This cytokine could be involved in the late phase of MM in vivo.
由于白细胞介素-10(IL-10)是一种可促使人类B细胞分化为成熟浆细胞的强效分化因子,我们研究了其对人类恶性浆细胞的作用。IL-10在四种依赖IL-6的人类恶性浆细胞系中未诱导任何分化,也未增加Ig合成。然而,在缺乏IL-6的情况下,它刺激了四种细胞因子依赖细胞系中的两种的增殖,并且已获得了依赖IL-10的骨髓瘤细胞系。IL-10的骨髓瘤细胞生长活性不受抗IL-6和抗IL-6R抗体的影响。同样,在来自活动性多发性骨髓瘤(MM)患者肿瘤样本的IL-6缺失培养物中,IL-10刺激(P = 0.001)了新植入的骨髓瘤细胞的增殖,并且在这些培养物中产生的骨髓瘤细胞数量增加了一倍。同样,这种细胞因子无法诱导新鲜骨髓瘤细胞进一步分化(通过Ig产生速率评估)。一种非常灵敏的酶联免疫吸附测定(ELISA;1 pg/mL)仅在极少数MM患者血清中检测到IL-10(89例中有3例)。相反,在60%的浆细胞白血病患者(20例中有12例)血清中检测到了IL-10。这些数据表明,IL-10是一种与IL-6无关的恶性浆母细胞生长因子。这种细胞因子可能参与了MM体内的晚期阶段。