Kist A, Ho A D, Räth U, Wiedenmann B, Bauer A, Schlick E, Kirchner H, Männel D N
Institutes of Virus Research, German Cancer Research Center, Heidelberg.
Blood. 1988 Jul;72(1):344-8.
Tumor necrosis factor (TNF), a protein predominantly produced by activated macrophages/monocytes, is presently available in recombinant, purified form for clinical trials. Intensive studies in many laboratories have shown that besides the tumorcytotoxic effects, TNF acts on a large array of different cells and has potent immunomodulatory activities. In a clinical phase I study, some immunologic functional parameters of blood cells from patients who received 24-hour infusions of recombinant human TNF (rhTNF) were analyzed. Natural killer (NK) cell activity, TNF production, interleukin-1 (IL-1) production and mitogen-induced proliferation were measured either in whole blood samples or in cultures of peripheral mononuclear leukocytes of the patients directly before and after rhTNF infusion. NK cell activity, TNF and IL-1 production capacity and proliferative responses to concanavalin A (Con A) were significantly reduced after rhTNF application. We conclude from these observations that rhTNF in vivo acts directly or indirectly on NK cells and monocytes by either inactivating their functional capacity or by absorbing the relevant cells to the endothelial cell layer, thus removing them from circulation.
肿瘤坏死因子（TNF）是一种主要由活化的巨噬细胞/单核细胞产生的蛋白质，目前已有重组纯化形式用于临床试验。许多实验室的深入研究表明，除了肿瘤细胞毒性作用外，TNF还作用于大量不同细胞，并具有强大的免疫调节活性。在一项I期临床研究中，分析了接受24小时重组人TNF（rhTNF）输注的患者血细胞的一些免疫功能参数。在rhTNF输注前后，直接在患者的全血样本或外周单核白细胞培养物中测量自然杀伤（NK）细胞活性、TNF产生、白细胞介素-1（IL-1）产生和有丝分裂原诱导的增殖。应用rhTNF后，NK细胞活性、TNF和IL-1产生能力以及对刀豆蛋白A（Con A）的增殖反应显著降低。我们从这些观察结果得出结论，体内rhTNF直接或间接作用于NK细胞和单核细胞，要么使其功能能力失活，要么将相关细胞吸附到内皮细胞层，从而使其从循环中清除。
