Levy Y, Tsapis A, Brouet J C
Laboratory of Immunochemistry and Immunopathology, Institut National de la Santé et de la Recherche Médicale U 108, Hôpital Saint-Louis, Paris, France.
J Clin Invest. 1991 Aug;88(2):696-9. doi: 10.1172/JCI115355.
IL-6 has been shown to be a plasmacytoma growth factor in mice and is believed to play a key role in the development of human multiple myeloma. We investigated the IL-6 requirements for the growth of two human myeloma cell lines, U 266 and RPMI 8226. These cell lines secreted minute amounts of IL-6 (20 U/ml) and featured IL-6 mRNA. IL-6 receptors were detectable at the surface of malignant cells by immunofluorescence. Antibodies to IL-6 did not alter the proliferation of these myeloma cells. There was a dose-dependent decrease, however, in [3H]-thymidine uptake in the presence of IL-6 antisense (and not sense) oligodeoxynucleotides; in the presence of 20 microM IL-6 antisense, an 80 and 95% inhibition of the proliferation of U 266 and RPMI 8226 cells was observed, respectively. These results provide strong evidence for an IL-6 autocrine proliferation of myeloma cells which may occur via internal interaction between IL-6 and the IL-6 receptor.
白细胞介素-6（IL-6）已被证明是小鼠浆细胞瘤生长因子，并且被认为在人类多发性骨髓瘤的发展中起关键作用。我们研究了两种人类骨髓瘤细胞系U 266和RPMI 8226生长所需的IL-6。这些细胞系分泌微量的IL-6（20 U/ml）并具有IL-6 mRNA。通过免疫荧光可在恶性细胞表面检测到IL-6受体。抗IL-6抗体并未改变这些骨髓瘤细胞的增殖。然而，在存在IL-6反义（而非正义）寡脱氧核苷酸的情况下，[3H] - 胸腺嘧啶核苷摄取呈剂量依赖性下降；在存在20 microM IL-6反义寡核苷酸的情况下，分别观察到U 266和RPMI 8226细胞增殖受到80%和95%的抑制。这些结果为骨髓瘤细胞的IL-6自分泌增殖提供了有力证据，这可能通过IL-6与IL-6受体之间的内部相互作用发生。
