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MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia

Nature volume 365, pages 756–759 (1993)Cite this article

A Correction to this article was published on 01 November 1995

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Abstract

CYTOKINES are critical in the often fatal cascade of events that cause septic shock1–3. One regulatory system that is likely to be important in controlling inflammatory responses is the neuroendocrine axis. The pituitary, for example, is ideally situated to integrate central and peripheral stimuli4, and initiates the increase in systemic glucocorticoids that accompanies host stress responses6–8. To assess further the contribution of the pituitary to systemic inflammatory processes, we examined the secretory profile of cultured pituitary cells and whole pituitaries in vivo after stimulation with bacterial lipopolysaccharide (LPS). Here we identify macrophage migration inhibitory factor (MIF)9–11 as a major secreted protein released by anterior pituitary cells in response to LPS stimulation. Serum analysis of control, hypophysectomized and T-cell-deficient (nude) mice suggests that pituitary-derived MIF contributes to circulating MIF present in the post-acute phase of endotoxaemia. Recombinant murine MIF greatly enhances lethality when co-injected with LPS and anti-MIF antibody confers full protection against lethal endotoxaemia. We conclude that MIF plays a central role in the toxic response to endotoxaemia and possibly septic shock.

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References

  1. Beutler, B. & Cerami, A. Nature 320, 584–588 (1986).

    Article  ADS  CAS  Google Scholar 

  2. Tracey, K. J. & Lowry, S. F. Adv. Surgery 23, 21–56 (1990).

    CAS  Google Scholar 

  3. Dinarello, C. A. J. infect. Dis. 163, 1177–1184 (1991).

    Article  CAS  Google Scholar 

  4. Koenig, J. I. et al. Endocrinology 126, 3053–3057 (1990).

    Article  CAS  Google Scholar 

  5. Besedovsky, H., Del Rey, A., Sorkin, E. & Dinarello, C. A. Science 233, 652–654 (1986).

    Article  ADS  CAS  Google Scholar 

  6. Reichlin, S. Williams Textbook of Endocrinology 8th edn. 135–219 (Saunders. Philadelphia, 1992).

    Google Scholar 

  7. Yasuda, N. & Greer, M. A. Endocrinology 102, 947–953 (1978).

    Article  CAS  Google Scholar 

  8. Makara, G. B., Stark, E. & Meszaros, T. Endocrinology 88, 412–417 (1971).

    Article  CAS  Google Scholar 

  9. Weiser, W. Y. et al. Proc. natn. Acad. Sci. U.S.A. 86, 7522–7526 (1989).

    Article  ADS  CAS  Google Scholar 

  10. Bloom, B. R. & Bennett, B. Science 153, 80–82 (1966).

    Article  ADS  CAS  Google Scholar 

  11. David, J. R. Proc. natn. Acad. Sci. U.S.A. 65, 72–77 (1966).

    Article  ADS  Google Scholar 

  12. Schumann, R. R. et al. Science 249, 1429–1431 (1990).

    Article  ADS  CAS  Google Scholar 

  13. Wright, S. D., Ramos, R. A. Tobias, P. S., Ulevich, R. J. & Mathison, J. C. Science 249, 1431–1433 (1990).

    Article  ADS  CAS  Google Scholar 

  14. Weiser, W. Y., Pozzi, L. M. & David, J. R. J. Immun. 147, 2006–2011 (1991).

    CAS  PubMed  Google Scholar 

  15. Pozzi, L. M. & Weiser, W. Y. Cell. Immun. 145, 372–379 (1992).

    Article  CAS  Google Scholar 

  16. Weiser, W. Y., Pozzi, L. M. Titus, R. G. & David, J. R. Proc. natn. Acad. Sci. U.S.A. 89, 8049–8052 (1992).

    Article  ADS  CAS  Google Scholar 

  17. Cunha, F. Q. et al. J. Immun. 150, 1908–1912 (1993).

    CAS  PubMed  Google Scholar 

  18. Thorner, M. O., Vance, M. L., Horvath, E. & Kovacs, K. Williams Textbook of Endocrinology 8th edn 221–310 (Saunders, Philadelphia, 1992).

    Google Scholar 

  19. Silverstein, R., Turley, B. R., Christoffersen, C. A., Johnson, D. C. & Morrison, D. C. J. exp. Med. 173, 357–365 (1991).

    Article  CAS  Google Scholar 

  20. Tracey, K. J., Vlassara, H. & Cerami, A. Lancet I, 1122–1126 (1989).

    Article  Google Scholar 

  21. Fraker, D. L., Stovroff, M. C., Merino, M. J. & Norton, J. A. J. exp. Med. 168, 95–105 (1988).

    Article  CAS  Google Scholar 

  22. Kriegler, M. Gene Transfer and Expression: A Laboratory Manual 219–221 (Freeman, New York, 1990).

    Book  Google Scholar 

  23. Boyden, S. V. J. exp. Med. 115 453–466 (1962).

    Article  CAS  Google Scholar 

  24. Alonso, S., Minty, A., Bourlet, Y. & Buckingham, M. J. molec. Evol. 23, 11–22 (1986).

    Article  ADS  CAS  Google Scholar 

  25. Gilliland, G., Perrin, S., Blanchard, K. & Bunn, H. F. Proc. natn. Acad. Sci. U.S.A. 87, 2725–2729 (1990).

    Article  ADS  CAS  Google Scholar 

  26. Li, B. et al. J. exp. Med. 174, 1259–1262 (1991).

    Article  CAS  Google Scholar 

  27. Heumann, D., Baumgartner, J. D., Jacot-Guillarmod, H. & Glauser, M. P. J. infect. Dis. 163, 762–768 (1991).

    Article  CAS  Google Scholar 

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Author notes

  1. R. Bucala: To whom correspondence should be addressed.

Authors and Affiliations

  1. The Picower Institute for Medical Research, 350 Community Drive, Manhasset, New York, 11030, USA

    J. Bernhagen, T. Calandra, R. A. Mitchell, K. J. Tracey, K. R. Manogue, A. Cerami & R. Bucala

  2. Physiologisch-chemisches Institut, University of Tübingen, W-7400, Tübingen, Germany

    J. Bernhagen & W. Voelter

  3. Division of Neurosurgery, New York Hospital–Cornell University Medical College, New York, New York, 10021, USA

    S. B. Martin

  4. Department of Surgery, North Shore University Hospital–Cornell University Medical College, Manhasset, New York, 11030, USA

    K. J. Tracey

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  1. J. Bernhagen
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Bernhagen, J., Calandra, T., Mitchell, R. et al. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 365, 756–759 (1993). https://doi.org/10.1038/365756a0

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