Philip R, Epstein L B
Nature. 1986;323(6083):86-9. doi: 10.1038/323086a0.
Activated monocytes or macrophages can release soluble cytotoxic molecules capable of lysing tumour cells in vitro and 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 alpha-IFN or gamma-IFN, and also interleukin (IL)-1 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 gamma-IFN, IL-1 and, in an autocrine manner, by TNF itself. Neither TNF, IL-1, gamma-IFN nor alpha-IFN mediate spontaneous monocyte cytotoxicity or that induced by alpha-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.
活化的单核细胞或巨噬细胞能够释放可溶的细胞毒性分子，这些分子在体外能够裂解肿瘤细胞，因此是宿主抗恶性肿瘤防御机制的重要组成部分。最近，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可得性，使得剖析这些因子在单核细胞诱导和执行细胞毒性事件中的相互作用成为可能。我们的研究表明，用α-干扰素或γ-干扰素以及白细胞介素（IL）-1或肿瘤坏死因子（TNF）预处理单核细胞会增强单核细胞的细胞毒性。尽管所有这些物质都会诱导单核细胞产生IL-1，但TNF介导γ-干扰素、IL-1以及TNF自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-干扰素和α-干扰素均不介导单核细胞的自发细胞毒性或α-干扰素诱导的细胞毒性。因此，我们的研究揭示了两种单核因子IL-1和TNF之间的新相互作用，并为TNF提供了双重作用，即作为免疫调节剂以及某些特定淋巴因子和单核因子分子诱导的单核细胞细胞毒性的介质。
