Nedwin G E, Svedersky L P, Bringman T S, Palladino M A, Goeddel D V
J Immunol. 1985 Oct;135(4):2492-7.
Human peripheral blood mononuclear cells (PBMC) were induced by recombinant interleukin 2 and mitogens to secrete two distinct cytotoxic polypeptides, tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta), previously called lymphotoxin. Treatment of PBMC with recombinant human interleukin 2 (rIL 2) or mitogens in combination with recombinant human interferon-gamma (rIFN-gamma) resulted in augmented production of both TNF-alpha and TNF-beta. rIFN-gamma alone had no effect on production of either cytotoxic polypeptide. TNF-alpha was produced within 2 to 3 hr after induction and was the major cytotoxin produced by PBMC during the first 48 hr of culture, after which time TNF-beta became the predominant species. TNF-beta was first secreted into the media after 8 hr of induction. Enhanced levels of both TNF-alpha and TNF-beta were seen when the PBMC were separated into adherent and nonadherent cells. Both TNF-alpha and TNF-beta were induced in different tumor cell lines of hematopoietic origin. The results demonstrate that the production of TNF-alpha and TNF-beta can be enhanced by two lymphokines, IL 2 and IFN-gamma.
重组白细胞介素2和丝裂原诱导人外周血单个核细胞（PBMC）分泌两种不同的细胞毒性多肽，即肿瘤坏死因子-α（TNF-α）和肿瘤坏死因子-β（TNF-β），后者以前称为淋巴毒素。用重组人白细胞介素2（rIL 2）或丝裂原与重组人干扰素-γ（rIFN-γ）联合处理PBMC，可增加TNF-α和TNF-β的产生。单独的rIFN-γ对两种细胞毒性多肽的产生均无影响。TNF-α在诱导后2至3小时内产生，是PBMC在培养的最初48小时内产生的主要细胞毒素，此后TNF-β成为主要种类。TNF-β在诱导8小时后首次分泌到培养基中。当将PBMC分离为贴壁细胞和非贴壁细胞时，TNF-α和TNF-β的水平均升高。TNF-α和TNF-β在不同造血来源的肿瘤细胞系中均被诱导产生。结果表明，两种淋巴因子IL 2和IFN-γ可增强TNF-α和TNF-β的产生。
