Männel D N, Kist A, Ho A D, Räth U, Reichardt P, Wiedenmann B, Schlick E, Kirchner H
Institute of Immunology and Genetics, German Cancer Research Centre, Heidelberg, FRG.
Br J Cancer. 1989 Oct;60(4):585-8. doi: 10.1038/bjc.1989.318.
Tumour necrosis factor (TNF) has been found to be an important immunomodulator. Among other functions TNF activates natural killer (NK) cells and stimulates monocytes/macrophages in an autocrine fashion. TNF production and NK activity in peripheral blood mononuclear cells were determined in a clinical phase I study in which recombinant human (rh) TNF was administered as a continuous infusion weekly for a period of 8 weeks. Even though TNF production and NK activity were significantly reduced directly after rhTNF infusion the effect proved to be transient and most pronounced at the first rhTNF administration. One day after completion of the rhTNF infusion the peripheral cells released more TNF into the supernatant compared to TNF activity immediately before the rhTNF infusion. This effect was conspicuous in non-stimulated cultures. After repeated rhTNF infusions both stimulated and non-stimulated TNF production of the peripheral blood mononuclear cells was increased. NK cell activity was also enhanced after repeated cycles of rhTNF administration as compared to early rhTNF treatment. Thus, repeated rhTNF infusions lead to a stimulatory effect on TNF production and NK activity of peripheral blood cells.
肿瘤坏死因子（TNF）已被发现是一种重要的免疫调节剂。除其他功能外，TNF以自分泌方式激活自然杀伤（NK）细胞并刺激单核细胞/巨噬细胞。在一项I期临床研究中测定了外周血单核细胞中的TNF产生和NK活性，在该研究中，重组人（rh）TNF每周连续输注8周。尽管在rhTNF输注后TNF产生和NK活性直接显著降低，但结果证明这种效应是短暂的，并且在首次给予rhTNF时最为明显。rhTNF输注完成一天后，与rhTNF输注前即刻的TNF活性相比，外周细胞向上清液中释放了更多的TNF。这种效应在未刺激的培养物中很明显。重复给予rhTNF后，外周血单核细胞的刺激和未刺激的TNF产生均增加。与早期rhTNF治疗相比，在重复rhTNF给药周期后NK细胞活性也增强。因此，重复输注rhTNF对外周血细胞的TNF产生和NK活性具有刺激作用。
