Bianchi A C, Heslop H E, Drexler H G, Cordingley F T, Turner M, De Mel W C, Hoffbrand A V, Brenner M K
Department of Haematology, Royal Free Hospital School of Medicine, London, UK.
Nouv Rev Fr Hematol (1978). 1988;30(5-6):317-9.
Tumour necrosis factor (TNF) induces the lysis of many malignant cells in vitro and regression of some tumours in vivo. However, TNF is also a growth factor for normal fibroblasts, T cells and B cells and we have recently shown that TNF can also act as a growth factor for chronic B cell neoplasms, including hairy cell leukaemia and B-CLL. In these cells it promotes proto-oncogene expression, RNA and DNA synthesis and increases overall cell survival. Stimulation appears to be autocrine in nature since exposure of the neoplastic cells to recombinant TNF protein induces the corresponding messenger RNA and synthesis of the protein itself. TNF induced proto-oncogene expression and DNA synthesis occur over a substantially longer time period than when the cells are stimulated with agents such as TPA and Calcium ionophore (2), but we have no evidence that the delay represents the time taken to generate TNF dependent secondary cytokines such as IL-1 and IL6. Alpha interferon opposes TNF mediated activation and our recent data indicate that this effect is independent of alpha interferon down regulation of TNF receptors. It appears to be related instead to a decreased accumulation of TNF mRNA which occurs contemporaneously with an alpha interferon induced rise in 2-5 A synthetase. If TNF dependent growth is important for the survival of B-CLL cells, then agents which mimic alpha interferon or which block TNF induced autocrine growth would be predicted to be of therapeutic benefit.
肿瘤坏死因子（TNF）在体外可诱导多种恶性细胞溶解，在体内能使一些肿瘤消退。然而，TNF也是正常成纤维细胞、T细胞和B细胞的生长因子，并且我们最近发现TNF对慢性B细胞肿瘤，包括毛细胞白血病和B细胞慢性淋巴细胞白血病（B-CLL），也可起到生长因子的作用。在这些细胞中，它能促进原癌基因表达、RNA和DNA合成，并提高细胞总体存活率。这种刺激似乎本质上是自分泌的，因为将肿瘤细胞暴露于重组TNF蛋白会诱导相应信使RNA的产生以及蛋白自身的合成。与用佛波酯（TPA）和钙离子载体等试剂刺激细胞相比，TNF诱导原癌基因表达和DNA合成所需的时间要长得多，但我们没有证据表明这种延迟代表生成诸如白细胞介素-1（IL-1）和白细胞介素-6（IL-6）等TNF依赖性次级细胞因子所需的时间。α干扰素可对抗TNF介导的激活作用，我们最近的数据表明这种效应与α干扰素下调TNF受体无关。相反，它似乎与TNF mRNA积累减少有关，这种减少与α干扰素诱导的2-5A合成酶升高同时发生。如果TNF依赖性生长对B-CLL细胞的存活很重要，那么模拟α干扰素或阻断TNF诱导的自分泌生长的药物预计将具有治疗益处。
