Impaired immune and acute-phase responses in interleukin-6-deficient mice (original) (raw)

Nature volume 368, pages 339–342 (1994)Cite this article

Abstract

lNTERLEUKIN-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria monocytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Van-Snick, J. A. Rev. Immun. 8, 253–278 (1990).
    Article CAS Google Scholar
  2. Kishimoto, T. Blood 74, 1–10 (1989).
    CAS PubMed Google Scholar
  3. Kishimoto, T., Akira, S. & Taga, T. Science 258, 593–597 (1992).
    Article ADS CAS Google Scholar
  4. Stahl, N. & Yancopolous, G. D. Cell 74, 587–590 (1993).
    Article CAS Google Scholar
  5. Rothstein, J. L. et al. Genes Dev. 6, 1190–1201 (1992).
    Article CAS Google Scholar
  6. Lotz, M. et al. J. exp. Med. 167, 1253–1258 (1988).
    Article CAS Google Scholar
  7. Uyttenhove, C., Coulie, P. G. & Van, S. J. J. exp. Med. 167, 1417–1427 (1988).
    Article CAS Google Scholar
  8. Gupta, S. L., Hengartner, H. & Zinkernagel, R. Proc. natn. Acad. Sci. U.S.A. 82, 2604–2608 (1986).
    Article ADS Google Scholar
  9. Suematsu, S. et al. Proc. natn. Acad. Sci. U.S.A. 86, 7547–7551 (1989).
    Article ADS CAS Google Scholar
  10. Leist, T. P., Kohler, M. & Zinkernagel, R. M. Scand. J. Immun. 30, 679–686 (1989).
    Article CAS Google Scholar
  11. Doherty, P. C., Allan, W. & Eichelberger, M. A. Rev. Immun. 10, 123–151 (1992).
    Article CAS Google Scholar
  12. Spriggs, M. K. et al. Proc. natn. Acad. Sci. U.S.A. 89, 6070–6074 (1992).
    Article ADS CAS Google Scholar
  13. Huang, S. et al. Science 259, 1742–1745 (1993).
    Article ADS CAS Google Scholar
  14. Ramsay, A. J., Ruby, J. & Ramshaw, I. A. Immun. Today 14, 155–157 (1993).
    Article CAS Google Scholar
  15. Kaufmann, S. A. Rev. Immun. 11, 129–163 (1993).
    Article CAS Google Scholar
  16. Liew, F. Y. & Cox, F. E. G. Immunoparasit. Today A17–A21 (1991).
  17. Beckerman, K. P. et al. J. Immun. 150, 888–895 (1993).
    CAS PubMed Google Scholar
  18. Gregory, S. H., Wing, E. J., Hoffman, R. A. & Simmons, R. L. J. Immun. 150, 2901–2909 (1993).
    CAS Google Scholar
  19. North, R. J. J. Immun. 121, 806–810 (1978).
    CAS PubMed Google Scholar
  20. Dalton, D. K. et al. Science 259, 1739–1742 (1993).
    Article ADS CAS Google Scholar
  21. Pfeffer, K. et al. Cell 73, 457–467 (1993).
    Article CAS Google Scholar
  22. Rothe, J. et al. Nature 364, 798–802 (1993).
    Article ADS CAS Google Scholar
  23. Havel, E. A., Moldawer, L. L., Helfgott, D., Kilian, P. L. & Sehgal, P. B. J. Immun. 148, 1486–1492 (1992).
    Google Scholar
  24. Koj, A. in Injury and Infection (eds Gordon, A. H. & Koj, A.) 145–160 (Elsevier, Amsterdam, 1985).
    Google Scholar
  25. Van Snick, J. et al. Proc. natn. Acad. Sci. U.S.A. 83, 9679–9683 (1986).
    Article ADS CAS Google Scholar
  26. Binder, D. & Kundig, T. M. J. Immun. 146, 4301–4307 (1991).
    CAS PubMed Google Scholar
  27. Blanden, R. V. & Langmann, R. E. Scand. J. Immun. 1, 379–391 (1972).
    Article CAS Google Scholar
  28. Ding, A. H., Nathan, C. F. & Stuehr, J. Immun. 141, 2407–2412 (1988).
    CAS PubMed Google Scholar
  29. Baumann, H., Latimer, J. J. & Glibetic, M. D. Arch. Biochem. Biophys. 246, 488–493 (1986).
    Article CAS Google Scholar
  30. Baumann, H. Meth. Enzym. 163, 566–594 (1988).
    Article CAS Google Scholar

Download references

Author information

Author notes

  1. Heinz Baumann: To whom correspondence should be addressed

Authors and Affiliations

  1. Max-Planck-lnstitut für Immunbiologie, Stübeweg 51, 79108, Freiburg, Germany
    Manfred Kopf, Marina Freudenberg, Marinus Lamers & Georges Köhler
  2. Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA
    Manfred Kopf & Georges Köhler
  3. Institut für Experimentelle Immunologie, Universität Zürich, Switzerland
    Giulia Freer & Rolf Zinkernagel
  4. Department of Biology, Hoffmann-La Roche AG, CH-4002, Basel, Switzerland
    Horst Bluethmann
  5. Department of Medicine III, Osaka University, Medical School, Osaka, 565, Japan
    Tadamitsu Kishimoto

Authors

  1. Manfred Kopf
    You can also search for this author inPubMed Google Scholar
  2. Heinz Baumann
    You can also search for this author inPubMed Google Scholar
  3. Giulia Freer
    You can also search for this author inPubMed Google Scholar
  4. Marina Freudenberg
    You can also search for this author inPubMed Google Scholar
  5. Marinus Lamers
    You can also search for this author inPubMed Google Scholar
  6. Tadamitsu Kishimoto
    You can also search for this author inPubMed Google Scholar
  7. Rolf Zinkernagel
    You can also search for this author inPubMed Google Scholar
  8. Horst Bluethmann
    You can also search for this author inPubMed Google Scholar
  9. Georges Köhler
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Kopf, M., Baumann, H., Freer, G. et al. Impaired immune and acute-phase responses in interleukin-6-deficient mice.Nature 368, 339–342 (1994). https://doi.org/10.1038/368339a0

Download citation