Fiers W, Beyaert R, Brouckaert P, Everaerdt B, Haegeman C, Suffys P, Tavernier J, Vanhaesebroeck B
Laboratorium voor Moleculaire Biologie, Rijksuniversiteit Gent, Belgium.
Dev Biol Stand. 1988;69:143-51.
Tumour Necrosis Factor (TNF) was discovered on the basis of its capability to induce necrosis of certain tumours in vivo. A brief overview is given of the pleiotropic effects of TNF on a variety of cells, either transformed cells or normal, diploid cells. Many transformed cells are killed by TNF, especially in the presence of interferon-gamma or inhibitors of transcription or translation. Various activities of TNF on normal cells have been studied, especially those on the endothelial system; these effects may be relevant to an understanding of its toxicity. TNF presumably acts by activation of phospholipase-A2. A number of genes are induced by TNF and, for example, many cells produce interleukin-6. The latter acts on B-cells, on T-cells, on bone marrow cells and, last but not least, on hepatocytes, which results in the synthesis of acute phase proteins. Although the toxicity of TNF, especially in the presence of interferon, limits its wide applicability, it can nevertheless lead to complete tumour curing in experimental animals. Reduction of its toxicity, e.g. by indomethacin treatment, opens new possibilities for TNF as an antitumour drug, alone or in combination with interferon.
肿瘤坏死因子（TNF）是基于其在体内诱导某些肿瘤坏死的能力而被发现的。本文简要概述了TNF对多种细胞（无论是转化细胞还是正常二倍体细胞）的多效性作用。许多转化细胞会被TNF杀死，尤其是在存在γ干扰素或转录或翻译抑制剂的情况下。TNF对正常细胞的各种活性已得到研究，尤其是对内皮系统的活性；这些作用可能与理解其毒性有关。TNF可能通过激活磷脂酶A2发挥作用。TNF可诱导许多基因，例如，许多细胞会产生白细胞介素-6。后者作用于B细胞、T细胞、骨髓细胞，而且尤其作用于肝细胞，这会导致急性期蛋白的合成。尽管TNF的毒性，尤其是在存在干扰素的情况下，限制了其广泛应用，但它仍可在实验动物中实现肿瘤的完全治愈。降低其毒性，例如通过吲哚美辛治疗，为TNF作为抗肿瘤药物单独使用或与干扰素联合使用开辟了新的可能性。
