TUMOR-NECROSIS-FACTOR AS IMMUNOMODULATOR AND MEDIATOR OF MONOCYTE CYTOTOXICITY INDUCED BY ITSELF, GAMMA-INTERFERON AND INTERLEUKIN-1
TUMOR-NECROSIS-FACTOR AS IMMUNOMODULATOR AND MEDIATOR OF MONOCYTE CYTOTOXICITY INDUCED BY ITSELF, GAMMA-INTERFERON AND INTERLEUKIN-1
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DOI：
10.1038/323086a0
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发表时间：
1986-09-04
期刊：
影响因子：
64.8
通讯作者：
EPSTEIN, LB
中科院分区：
文献类型：
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作者：
PHILIP, R;EPSTEIN, LB
活化的单核细胞或巨噬细胞可以释放可溶性细胞毒性分子，能够在体外溶解肿瘤细胞1 - 6，因此是宿主防御恶性肿瘤机制的重要组成部分。纯重组或天然人淋巴因子和单核因子及其各自的多克隆或单克隆抗体的最近可用性现在使得有可能剖析这些因子在单核细胞诱导和表现细胞毒性事件中的相互作用。我们的研究表明，用α-IFN或γ-IFN以及白细胞介素（IL）-1或肿瘤坏死因子（TNF）预处理单核细胞可增强单核细胞的细胞毒性。尽管所有这些物质都诱导单核细胞产生IL-1，但TNF介导γ-IFN、IL-1以及TNF本身以自分泌方式诱导的单核细胞增强的细胞毒性。TNF、IL-1、γ-IFN和α-IFN均不介导自发性单核细胞毒性或α-IFN诱导的单核细胞毒性。因此，我们的研究揭示了两种单核因子IL-1和TNF之间的新的相互作用，并提供了TNF的双重作用，作为某些特定的淋巴因子和单核因子分子诱导的单核细胞毒性的免疫调节剂和介体。
Activated monocytes or macrophages can release soluble cytotoxic molecules capable of lysing tumour cellsin vitro1–6and thus represent an important component of the host defence mechanisms against malignancy. The recent availability of pure recombinant or natural human lymphokines and monokines and their respective polyclonal or monoclonal antibodies now makes it possible to dissect the interactions of these factors in the induction and performance of the cytotoxic event by the monocytes. Our studies indicate that pretreatment of monocytes with α-IFN or γ-IFN, and also interleukin (IL)-l or tumour necrosis factor (TNF) results in enhanced monocyte cytotoxicity. Although all these substances induce the production of IL-1 by monocytes, TNF mediates the enhanced cytotoxicity induced in monocytes by γ-IFN, IL-1 and, in an autocrine manner, by TNF itself. Neither TNF, IL-1, γ-IFN nor α-IFN mediate spontaneous monocyte cytotoxicity or that induced by α-IFN. Our studies thus reveal new interactions between the two monokines IL-1 and TNF and provide a dual role for TNF, as immunomodulator and mediator of monocyte cytotoxicity induced by certain specific lymphokine and monokine molecules.