Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Identity of tumour necrosis factor and the macrophage-secreted factor cachectin

Abstract

In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system1–3. Among these changes, a hypertrigly-ceridaemic state is frequently evident4–9, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL)9. We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells)10–17. When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a pI of 4.7, a subunit size of relative molecular mass (Mr) 17,000 and to form non-covalent multimers17. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes17. A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF)18,19. Purified cachectin also possesses potent TNF activity in vitro. These findings suggest that the ‘cachectin’ and ‘TNF’ activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Purchase on Springer Link

Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Beisel, W. R. A. Rev. Med. 26, 9–20 (1975).

    Article  CAS  Google Scholar 

  2. Filkins, J. P. J. reticuloendothel. Soc. 25, 591–595 (1979); 27, 507–511 (1980); in Patho-physiology of the Reticuloendothelial System (eds Altura, B. M. & Saba, T. M.) 93–110 (Raven, New York, >1981); Fedn Proc. 44, 300–304 (1985).

    Google Scholar 

  3. Dinarello, C. A. New Engl. J. Med. 311, 1413–1418 (1984); in Advances in Inflammation Research 8th edn (ed. Weissmann, G.) 203–225 (Raven, New York, (1984).

    Google Scholar 

  4. Hirsch, R. L., McKay, D. G., Travers, R. I. & Skraly, R. K. J. Lipid Res. 5, 563–568 (1964).

    CAS  PubMed  Google Scholar 

  5. Farshtchi, D. & Lewis, V. J. J. Bact. 95, 1615–1621 (1968).

    Article  CAS  Google Scholar 

  6. Gallin, J. I., Kaye, D. & O'Leary, W. M. New Engl. J. Med. 281, 1081–1086 (1969).

    Article  CAS  Google Scholar 

  7. Thoen, C. O., Karlson, A. G. & Ellefson, R. D. Mayo Clin. Proc. 47, 258–269, 270–272 (1972).

    CAS  PubMed  Google Scholar 

  8. Guy, M. W. Trans. R. Soc. trop. Med. Hyg. 69, 429 (1975).

    Google Scholar 

  9. Rouzer, C. A. & Cerami, A. Molec. biochem. Parasit. 2, 31–38 (1980).

    Article  CAS  Google Scholar 

  10. Kawakami, M. & Cerami, A. J. exp. med. 154, 631–639 (1981).

    Article  CAS  Google Scholar 

  11. Kawakami, M., Pekala, P. H., Lane, M. D. & Cerami, A. Proc. natn. Acad. Sci. U.S.A. 79, 912–916 (1982).

    Article  ADS  CAS  Google Scholar 

  12. Hotez, P. J., Le Trang, N., Fairlamb, A. H. & Cerami, A. Parasite Immun. 6, 203–209 (1984).

    Article  CAS  Google Scholar 

  13. Beutler, B., Mahoney, J., Pekala, P., Le Trang, N. & Cerami, A. Blood 64, 65a (1984).

    Google Scholar 

  14. Kawakami, M., Ikeda, Y., Le Trang, N., Vine, W. & Cerami, A. Proc. IUPHAR 2nd edn (ed. Patton, W.) 377–384 (Macmillan, London, 1984).

  15. Beutler, B., Mahoney, J., Le Trang, N., Pekala, P. & Cerami, A. Fedn Proc. 44, 1704 (1985).

    Google Scholar 

  16. Mahoney, J. et al. J. Immun. 134, 1673–1675 (1985).

    CAS  PubMed  Google Scholar 

  17. Beutler, B., Mahoney, J., Le Trang, N., Pekala, P. & Cerami, A. J. exp. Med. 161, 984 (1985).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  19. Shirai, T., Yamaguchi, H., Ito, H., Todd, C. W. & Wallace, R. B. Nature 313, 803–806 (1985).

    Article  ADS  CAS  Google Scholar 

  20. Green, H. & Kehinde, O. Cell 3, 114–116 (1974).

    Article  Google Scholar 

  21. Green, H. & Meuth, M. Cell 3, 127–133 (1974).

    Article  CAS  Google Scholar 

  22. Ruff, M. R. & Gifford, G. E. in Lymphokines Vol. 2 (ed. Pick, E.) 235–272 (Academic, New York 1981).

    Google Scholar 

  23. Aggarwal, et al. J. biol. Chem. 260, 2345–2354 (1985).

    CAS  PubMed  Google Scholar 

  24. Pan, Y-C. E., Wideman, J., Blacher, R., Chang, M. & Stein, S. J. Chromatogr. 297, 13–19 (1984).

    Article  CAS  Google Scholar 

  25. Pekala, P. H., Kawakami, M., Angus, C. W., Lane, M. D. & Cerami, A. Proc. natn. Acad. Sci. U.S.A. 80, 2743–2747 (1983).

    Article  ADS  CAS  Google Scholar 

  26. Lefkowitz, R. J., Roth, J. & Pastan, I. Science 170, 633–635 (1970).

    Article  ADS  CAS  Google Scholar 

  27. Wray, W., Boulikas, T., Wray, V. P. & Hancock, R. Analyt. Biochem. 118, 197–203 (1981).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beutler, B., Greenwald, D., Hulmes, J. et al. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 316, 552–554 (1985). https://doi.org/10.1038/316552a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/316552a0

This article is cited by

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing