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Emotions and disease: From balance of humors to balance of molecules

A new field of research investigates how the Immune and nervous systems communicate with each other.

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References

  1. Kuhn, T.S. The structure of scientific revolutions. in International encyclopedia of unified science. Foundations of the unity of science vol. 2 (University of Chicago Press, Chicago, 1970.)

    Google Scholar 

  2. Cortnummius, J. De Morto Attonito Liber Unus. (Leipzig, 1677).

    Google Scholar 

  3. Brown, T.M., Mental Disease. in Companion Encyclopedia of the History of Medicine vol. 1 (eds. Bynum, W.F. & Porter, R.) (Routledge, London, 1993).

    Google Scholar 

  4. Willis, T., Works of Thomas Willis. (London, 1679).

    Google Scholar 

  5. Felten, S.Y. & Felten, D.L. Innervation of lymphoid tissue. in Psychoneuroimmunology (eds. Ader, R., Felten, D.L. & Cohen N.) 27–61 (Academic Press, San Diego, 1991).

    Chapter  Google Scholar 

  6. Goetzl, E.J., Chernov, T., Renold, F. & Payan, D.G. Neuropeptide regulation of the expression of immediate hypersensitivity. J. Immunol. 135 (Suppl. 2) (1985).

  7. Berkenbosch, F., Oers, v.j., Rey, dA., Tilders, F. & Besedovsky, H. Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science 238, 524–536 (1987).

    Article  CAS  Google Scholar 

  8. Sapolsky, R., Rivier, C., Yamamoto, G., Plotsky, P. & Vale, W. Interleukin-1 stimulates the secretion of hypothalamic corticotropin releasing factor. Science 238, 522–524 (1987).

    Article  CAS  Google Scholar 

  9. Bernton, E.W., Beach, J.E., Holaday, J.W., Smallridge, R.C. & Fein, H.G. Release of multiple hormones by a direct action of interleukin-1 on pituitary cells. Science 238, 519–521 (1987).

    Article  CAS  Google Scholar 

  10. Payan, D.G. & Goetzl, E.J. Substance P receptor-dependent responses of leukocytes in pulmonary inflammation. Am. Rev. Respir. Dis. 136, 39–43 (1987).

    Article  Google Scholar 

  11. Sundar, S.K. et al. Intracerebroventricular infusion of interleukin-1 rapidly decreases peripheral cellular immune responses. Proc. Natl. Acad. Sci. USA 86, 6398–6402 (1989).

    Article  CAS  Google Scholar 

  12. Wick, G. et al. The multi-factorial pathogenesis of autoimmune disease. Immunol. Lett. 16, 249–257 (1987).

    Article  CAS  Google Scholar 

  13. Sternberg, E.M. et al. A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc. Natl. Acad. Sci. USA 86, 4771–775 (1989).

    Article  CAS  Google Scholar 

  14. Sternberg, E.M. et al. Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc. Natl. Acad. Sci. USA 86, 2374–2378 (1989).

    Article  CAS  Google Scholar 

  15. Edwards, C.K.I., Yunger, L.M., Lorence, R.M., Dantzer, R. & Kelley, K.W. The pituitary gland is required for protection against lethal effects of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 88, 2274–2277 (1991).

    Article  CAS  Google Scholar 

  16. MacPhee, I.A.M., Antoni, F.A. & Mason, D.W. Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids. J. Exp. Med. 169, 431–445 (1989).

    Article  CAS  Google Scholar 

  17. Misiewicz, B. et al. Intracerebroventricular transplantation of embryonic neuronal tissue from inflammatory resistant into inflammatory susceptible rats suppresses specific components of inflammation. Exp. Neurol. (in the press).

  18. Bartfai, T. & Schultzberg, M. Cytokines in neuronal cell types. Neurochem. Int. 22, 435–444 (1993).

    Article  CAS  Google Scholar 

  19. Sei, Y., Vitkovic, L. & Yokoyama, M.M. Cytokines in the central nervous system: Regulatory roles in neuronal function, cell death and repair. Neuroimmunomodulation 2, 121–133 (1995).

    Article  CAS  Google Scholar 

  20. Breder, C.D., Dinarello, C.A. & Saper, C.B. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science 240, 321–324 (1988).

    Article  CAS  Google Scholar 

  21. Ericsson, A., Liu, C., Hart, R.P. & Sawchenko, P.E. Type 1 interleukin-1 receptor in the rat brain: distribution, regulation, and relationship to sites of IL-1-induced cellular activation. J. Comp. Neurol. 361, 681–698 (1995).

    Article  CAS  Google Scholar 

  22. Takao, T., Tracey, D.E., Mitchell, W.M. & DeSouza, E.B. Interleukin-1 receptors in mouse brain: Characterization and neuronal localization. Endocrinol. 127, 3070–3078 (1990).

    Article  CAS  Google Scholar 

  23. Licinio, J., Wong, M.L. & Gold, P.W. Localization of interleukin-1 receptor antagonist mRNA in rat brain. Endocrinology 129, 562–564 (1991).

    Article  CAS  Google Scholar 

  24. Brenneman, D., Schultzberg, M., Bartfai, T. & Cozes, I. Cytokine regulation of neuronal cell survival. J. Neurochem. 58, 454–460 (1992).

    Article  CAS  Google Scholar 

  25. Watkins, L.R. et al. Characterization of cytokine-induced hyperalgesia. Brain Res. 654, 15–26 (1994).

    Article  CAS  Google Scholar 

  26. Bluthe, R.M. et al. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad. Sci. 317, 499–503 (1994).

    CAS  Google Scholar 

  27. Wong, M. & Licinio, J. Localization of interleukin-1 type I receptor mRNA in rat brain. Neuroimmunomodulation 1, 110–115 (1994).

    Article  CAS  Google Scholar 

  28. Breder, C.D. & Saper, C.B. Expression of inducible cyclooxygenase mRNA in the mouse brain after systemic administration of bacterial lipopolysaccharide. Brain Res. 713, 64–69 (1996).

    Article  CAS  Google Scholar 

  29. Scammell, T.E., Elmquist, J.K., & Saper, C.B. Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever. Am. J. Physiol. 271, 333–338 (1996).

    Google Scholar 

  30. Wong, M.L. et al. Inducible nitric oxide synthase gene expression in the brain during systemic inflammation. Nature Med. 2, 581–584 (1996).

    Article  CAS  Google Scholar 

  31. Brady, L.S., Lynn, A.B., Herkenham, M. & Gottesfeld, Z. Systemic interleukin-1 induces early and late patterns of c-fos mRNA expression in brain. J. Neurosci. 14, 4951–1964 (1994).

    Article  CAS  Google Scholar 

  32. Ericsson, A., Kovacs, K.J. & Sawchenko, P.E. A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neu-roendocrine neurons. J. Neurosci. 14, 897–913 (1994).

    Article  CAS  Google Scholar 

  33. Elmquist, J.K., Scammell, T.E., Jacobson, C.D. & Saper, C.B. Distribution of Fos-like immunoreactivity in the rat brain following intravenous lipopolysaccharide administration. J. Comp. Neurol. 371, 85–103 (1996).

    Article  CAS  Google Scholar 

  34. Campbell, I.L. Neuropathogenic actions of cytokines assessed in transgenic mice. Int. J. Dev. Neurosci. 13, 275–284 (1995).

    Article  CAS  Google Scholar 

  35. Evans, S.R. & Cidlowski, J.A. Regulation of apoptosis by steroid hormones. J. Steroid Biochem. Mol. Biol. 53, 1–8 (1995).

    Article  Google Scholar 

  36. King, L.B. et al. A targeted glucocorticoid receptor antisense transgene increases thymocyte apoptosis and alters thymocyte development. Immunity 3, 647–656 (1995).

    Article  CAS  Google Scholar 

  37. Hermann, G., Tovar, C.A., Beck, F.M., Allen, C. & Sheridan, J.F. Restraint stress differentially affects the pathogenesis of an experimental influenza viral infection in three inbred strains of mice. J. Neuroimmunol. 47, 83–94 (1993).

    Article  CAS  Google Scholar 

  38. Brown, D.H., Sheridan, J., Pearl, D. & Zwilling, B.S. Regulation of mycobacterial growth by the hypothalamus-pituitary-adrenal axis: differential responses of Mycobacterium bovis BCG-resistant- and -susceptible mice. Infect. Immun. 61, 4793–4800 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Brown, D.H., LaFuse, W.P. & Zwilling, B.S. Stabilized expression of mRNA is associated with mycobacterial resistance controlled by Nrampl. Infect. Immun. (in the press).

  40. Michelson, D. et al. Bone mineral density in women with depression. New Engl. J. Med. 335, 1177–1181 (1996).

    Article  Google Scholar 

  41. Cruwys, S.C., Garrett, N.E. & Kidd, B.L. Sensory denervation with capsaicin attenuates inflammation and nociception in arthritic rats. Neurosci, Lett. 193, 205–207 (1995).

    Article  CAS  Google Scholar 

  42. Matucci, C.M., McCarthy, G., Lombardi, A., Pignone, A., StPartsch, G. Neurogenic influences in arthritis:potentialmodificationby capsaicin. J. Rheumatol. 22, 1447–1449 (1995).

    Google Scholar 

  43. Thyagarajan, S., Felten, S., & Felten, D. Deprenyl partially restores the age-related loss of sympathetic noradrenergic innervation in the spleens of F344 rats. Society for Neuroscience Abstracts 22, 1793 (1996).

  44. McMurray, R.W., Weidensaul, D., Allen, S.H. & Walker, S.E. Efficacy of bromocriptine in an open label therapeutic trial for systemic lupus erythematosus. J. Rheumatol. 22, 2084–2091 (1995).

    CAS  PubMed  Google Scholar 

  45. Eitan, S. et al. Recovery of visual response of injured adult rat optic nerves treated with transglutaminase. Science 264, 1764–1768 (1994).

    Article  CAS  Google Scholar 

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Sternberg, E. Emotions and disease: From balance of humors to balance of molecules. Nat Med 3, 264–267 (1997). https://doi.org/10.1038/nm0397-264

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