Letter | Published:

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

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Matthews, N. Immunology 44, 135–142 (1981).

  2. 2

    Cameron, D. J. J. reticuloendothel. Soc. 32, 247–256 (1982).

  3. 3

    Reidarson, T. H., Levy, W. III, Klostergaard, J. & Granger, G. A. J. natn. Cancer Inst. 69, 879–887 (1982).

  4. 4

    Adams, D. O. & Nathan, C. F. Immun. Today 4, 166–170 (1983).

  5. 5

    Sone, S., Tachibana, K., Ishii, K., Ogawara, M. & Tsubura, E. Cancer Res. 44, 646–651 (1984).

  6. 6

    McKinnon, K. P., Chen, A. R., Argov, S., Love, B. & Koren, H. S. Immunobiology 171, 26–44 (1986).

  7. 7

    Colotta, F., Peri, G., Villa, A. & Mantovani, A. J. Immun. 132, 936–944 (1984).

  8. 8

    Ziegler-Heitbrock, H. W. L. & Reithmuller, G. J. natn. Cancer Inst. 72, 23–29 (1984).

  9. 9

    Koren, H. S. & Herberman, R. B. J. Leuk. Biol. 38, 441–445 (1985).

  10. 10

    Cameron, D. J. & Churchill, W. H. J. Immun. 124, 708–712 (1980).

  11. 11

    Peri, G., Polentarutti, N., Sessa, C., Mangioni, C. & Mantovani, A. Int. J. Cancer 28, 143–152 (1981).

  12. 12

    Herberman, R. B. et al. Cell Immun. 67, 160–167 (1982).

  13. 13

    Le, J. et al. J. Immun. 131, 2821–2826 (1983).

  14. 14

    Blasi, E., Herberman, R. B. & Varesio, L. J. Immun. 132, 3226–3228 (1984).

  15. 15

    Celada, A., Gray, P. W., Rinderknecht, E. & Schreiber, R. D. J. exp. Med. 60, 55–74 (1984).

  16. 16

    Orchansky, P., Rubenstein, M. & Fischer, D. G. J. Immun. 136, 169–173 (1986).

  17. 17

    Onozaki, K., Matsushima, K., Kleinerman, E. S., Saito, T. & Oppenheim, J. J. J. Immun. 135, 314–320 (1985).

  18. 18

    Oppenheim, J. J. & Gery, I. Immun. Today 125, 113–119 (1982).

  19. 19

    Herman, J., Kew, M. C. & Rabson, A. Cancer Immun. Immunother. 16, 182–185 (1984).

  20. 20

    Wallis, R. S., Fujiwara, H. & Ellner, J. J. J. Immun. 136, 193–196 (1986).

  21. 21

    Arenzana-Seisdedos, F., Virelizier, J. L. & Fiers, W. J. Immun. 134, 2444–2448 (1985).

  22. 22

    Haq, A. U., Rinehart, J. J. & Maca, R. D. J. Leuk. Biol. 38, 735–746 (1985).

  23. 23

    Candler, R. V., Rouse, B. T. & Moore, R. N. J. Interferon Res. 5, 179–189 (1985).

  24. 24

    Roberts, N. J., Douglas, R. G., Simons, R. L. & Diamond, M. E. J. Immun. 123, 446–450 (1980).

  25. 25

    Saksela, E., Virtanen, I., Hovi, T., Secher, D. S. & Cantell, K. Prog. med. Virol. 30, 78–86 (1984).

  26. 26

    Dinarello, C. A. J. clin. Immun. 5, 287–297 (1985).

  27. 27

    Carswell, E. A. et al. Proc. natn. Acad. Sci. U.S.A. 72, 3666–3670 (1975).

  28. 28

    Kelker, H. C. et al. Int. J. Cancer 36, 69–73 (1985).

  29. 29

    Chen, A. R., McKinnon, K. P. & Koren, H. S. J. Immun. 135, 3978–3987 (1985).

  30. 30

    Kildahl-Andersen, O., Espevik, T. & Nissen-Meyer, J. Cell. Immun. 95, 392–406 (1985).

  31. 31

    Staehelin, T., Hobbs, D. S., Kung, H.-F., Lai, C. Y. & Pestka, S. J. biol. Chem. 256, 9750–9754 (1981).

  32. 32

    Gray, P. W. et al. Nature 295 503–508 (1982).

  33. 33

    Rosenwasser, L. & Dinarello, C. Cell Immun. 63, 134–142 (1981).

  34. 34

    Pennica, D. et al. Nature 312 724–729 (1984).

  35. 35

    Boyum, A. Scand, J. clin. Lab. Invest. 21, Suppl. 97, 77–89 (1968).

  36. 36

    Kaye, J. & Janeway, C. A., Jr Lymphokine Res. 3, 175–182 (1984).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.