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Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, γ-interferon and interleukin-1

Nature volume 323, pages 86–89 (1986)Cite this article

Abstract

Activated monocytes or macrophages can release soluble cytotoxic molecules capable of lysing tumour cells in vitro1–6 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 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.

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Authors and Affiliations

  1. Cancer Research Institute and Department of Pediatrics, University of California, San Francisco, California, 94143, USA

    Ramila Philip & Lois B. Epstein

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  1. Ramila Philip
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  2. Lois B. Epstein
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Philip, R., Epstein, L. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, γ-interferon and interleukin-1. Nature 323, 86–89 (1986). https://doi.org/10.1038/323086a0

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