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Effects of Cytokines on Glucocorticoid Receptor Expression And Function

Glucocorticoid Resistance and Relevance to Depression
  • Andrew H. Miller
  • Carmine M. Pariante
  • Bradley D. Pearce
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 461)

Abstract

A large body of data has been amassed which convincingly demonstrates that the immune system and the nervous system extensively interact (Ader, Cohen, & Felten, 1991; Miller, In Press). Immune cells and tissues express receptors for a wide range of transmitters associated with and regulated by the nervous system including neuro-transmitters, peptides and hormones, and nervous system innervation of lymphoid tissues has been well characterized. Moreover, the presence of soluble immune products (cytokines) and their receptors have been found in multiple nervous system and endocrine tissues (Besedovsky & del Rey, 1996). Alterations of nervous system function by exposure to a variety of stressors has been shown to result in dramatic changes in immune system function, and exposure to cytokines or various types of immune activation has been shown to significantly alter CNS function (Miller, In Press; McEwen, Biron, Brunson, Bulloch, Chambers, Dhabhar, Goldfarb, Kitson, Miller, Spencer, & Weiss, 1997; Kent, Bluthe, Kelley, & Dantzer, 1992). Given the vast potential for mutual regulation involving the immune system and the brain, there has been considerable interest in the possibility that immune system processes may be involved in the pathophysiology of psychiatric syndromes including major depression. One possible mechanism whereby the immune system might contribute to the development of pathology which manifests as depressive symptomatology involves the capacity of cytokines to inhibit functioning of the receptors for glucocorticoids, thus inducing a state of glucocorticoid resistance.

Keywords

Major Depression Glucocorticoid Receptor Immune Activation Hypothalamic Pituitary Adrenal Axis Corticotropin Release Hormone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ader, R., Cohen, N., & Feiten, D. (1991). Psychoneuroimmunology II. New York, Academic Press.Google Scholar
  2. Besedovsky, H. O. & del Rey, A. (1996). Immune-neuro-endocrine interactions: Facts and hypotheses. Endocrine Reviews, 17, 64–102.PubMedCrossRefGoogle Scholar
  3. Dunn, A.J. & Wang. J. (1995). Cytokine effects on CNS biogenic amines. Neuroimmunomodulation, 2, 319–328.PubMedCrossRefGoogle Scholar
  4. Ericsson, A., Kovacs, J., & Sawchenko, P. E. (1994). A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons. Journal of Neuroscience, 14, 897–913.PubMedGoogle Scholar
  5. Guiochon-Mantel, A., Delabre, K., Lescop, P., & Milgrom, E. (1996). Intracellular traffic of steroid hormone receptors. Journal of Steroid Biochemistry and Molecular Biology, 56, 3–9.PubMedCrossRefGoogle Scholar
  6. Holsboer, F. & Barden, N. (1996). Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocrine Reviews, 17, 187–205.PubMedCrossRefGoogle Scholar
  7. Kent. S., Bluthe. R. M., Kelley, K. W., & Dantzer, R. (1992). Sickness behavior as a new target for drug development. Trends in Pharmacological Sciences, 13, 24–28.PubMedCrossRefGoogle Scholar
  8. Labeur, M.S., Arzt, E., Wiegers, G. J., Holsboer, F., & Reul, J. M. H. M. (1995). Long-term intracerebroven-tricular corticotropin-releasing hormone administration induces distinct changes in rat splenocyte activation and cytokine expression. Endocrinology, 136, 2678–2688.PubMedCrossRefGoogle Scholar
  9. Maes. M. (1993). A review on the acute phase response in major depression. Reviews in the Neurosciences, 4, 407–416.PubMedGoogle Scholar
  10. Maes. M., Meltzer, H. Y., Bosmans, E., Bergmans, R., Vandoolaeghe, E., Ranjan, R., & Desnyder, R. (1995). Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2, and transferrin receptor in major depression. Journal of Affective Disorders. 34, 301–309.PubMedCrossRefGoogle Scholar
  11. McEwen, B.S., Biron, C. A., Brunson, K. W., Bulloch, K., Chambers, W. H., Dhabhar, F. S., Goldfarb, R. H., Kitson. R. P., Miller. A. H., Spencer, R. L., & Weiss, J. M. (1997). The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine, and immune interactions. Brain Research Reviews, 23, 79–133.PubMedCrossRefGoogle Scholar
  12. Miller, A. H., Pearce. B. D., Ruzek, M. C., & Biron, C. A. (In Press). Interactions between the hypothalamic-pituitary-adrenal axis and immune system during viral infection: pathways for environmental effects on disease expression. In B. S. McEwen (Ed.), Handbook of Physiology.Google Scholar
  13. Miller. A.H. (1998). Neuroendocrine and immune system interactions in stress and depression. Psychiatric Clinics of North America. Philadelphia, W. B. Saunders, 21, 443–463.Google Scholar
  14. Miller, A.H., Spencer, R. L., Tanapat, P., Leung, J. J., Dhabhar, F. S., McEwen, B. S., & Biron, C. A. (1997). Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues. Psychoneuroendocrinology. 22, 455–474.PubMedCrossRefGoogle Scholar
  15. Musselman, D.L., Pisell. T. L., Lewison, B., Pearce, B. D., Knight, B.T., Ninan, P. T., Nemeroff, C. B., & Miller, A. H. (1997). Interleukin-6 plasma concentrations in cancer patients with depression. Society for Neuroscience Abstract, 23, 996.Google Scholar
  16. Norbiato, G., Bevilacqua, M., & Vago, T. (1997). Glucocorticoids and the immune system in AIDS. Psychoneuroendocrinology, 22, S19–S25.PubMedCrossRefGoogle Scholar
  17. Owens, M.J. & Nemeroff, C.B. (1993). The role of CRF in the pathophysiology of affective disorders: laboratory and clinical studies, Ciba Foundation Symposium on Corticotropin-Releasing Factor 172 (W. W. Vale, Ed.), New York, John Wiley & Sons, 293–316.Google Scholar
  18. Pariante.
    C.M., Pearce, B. D., Pisell, T. L., & Miller, A. H. (1996). Interleukin-1 alpha inhibits neucleocyto-plasmic traffic of the glucocorticoid receptor. International Congress of the International Society for Neuroimmunomodulation Abstract.Google Scholar
  19. Pariante, C.M., Nemeroff, C. B., & Miller, A. H. (1995). Glucocorticoid receptors in depression. Israel Journal of Medical Science, 31, 705–712.Google Scholar
  20. Pariante, C.M., Pearce, B. D., Pisell, T. L., Owens, M. J., & Miller, A. H. (1997). Steroid-Independent translocation of the glucocorticoid receptor by the antidepressant desipramine. Molecular Pharmacology, 52, 571–581.PubMedGoogle Scholar
  21. Pepin, M.C., Pothier, F., & Barden, N. (1992). Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression, Molecular Pharmacology, 42, 991–995.PubMedGoogle Scholar
  22. Pepin, M.-C., Govindan, M. V., & Barden, N. (1992). Increased glucocorticoid receptor gene promoter activity after antidepressant treatment. Molecular Pharmacology, 41, 1016–1022.PubMedGoogle Scholar
  23. Ribeiro, S. C. M., Tandon, R., Grunhaus, L., & Greden, J. F. (1993). The DST as a predictor of outcome in depression: a meta-analysis. American Journal of Psychiatry, 150, 1618–1629.PubMedGoogle Scholar
  24. Rivier, C. (1995). Influence of immune signals on the hypothalamic-pituitary axis of the rodent. Frontiers in Neuroendocrinology, 16, 151–182.PubMedCrossRefGoogle Scholar
  25. Rossby, S. P., Nalepa, I., Huang, M., Perrin, C., Burt, A. M., Schmidt, D. E., Gillespie, D. D., & Sulser, F. (1995). Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant. Brain Research, 687, 79–82.PubMedCrossRefGoogle Scholar
  26. Ruzek, M., Miller, A. H., Pearce, B. D., Spencer, R. L., & Biron, C. A. (1997). Evidence for endogenous glucocorticoid protection against MCMV-induced lethality. Society for Neuroscience Abstract, 23, 715.Google Scholar
  27. Ruzek, M.C., Miller, A. H., Opal, S. M., Pearce, B. D., & Biron, C. A. (1997). Characterization of early cytokine responses and an IL-6-dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection. Journal of Experimental Medicine, 185, 1185–1192.PubMedCrossRefGoogle Scholar
  28. Schulte, H. M., Bamberger, C. M., Elsen, H., Herrmann, G., Bamberger, ••, & Barth, J. (1994). Systemic interleukin-a alpha and interleukin-2 secretion in response to acute stress and to corticotropin-releasing hormomone in humans. European Journal of Clinical Investigation, 24, 773–777.PubMedGoogle Scholar
  29. Sluzewska, A., Rybakowski, J., Bosmans, E., Sobieska, M., Berghmans, R., Maes, M., & Wiktorowicz, K. (1996). Indicators of immune activation in major depression. Psychiatry Research, 64, 161–167.PubMedCrossRefGoogle Scholar
  30. Spencer, R. L., Miller, A. H., Stein, M., & McEwen, B. S. (1991). Corticosterone regulation of type I and type II adrenal steroid receptors in brain, pituitary, and immune tissue. Brain Research, 549, 236–246.PubMedCrossRefGoogle Scholar
  31. Weidenfeld, J. & Yirmiya, R. (1996). Effects of bacterial endotoxin on the glucocorticoid feedback regulation of adrenocortical response to stress. Neuroimmunomodulation, 3, 352–357.PubMedCrossRefGoogle Scholar
  32. Yirmiya, R. (1996). Endotoxin produces a depressive-like episode in rats. Brain Research, 711, 163–174.PubMedCrossRefGoogle Scholar
  33. Zhou, D., Kusnecov, A. W., Shurin, M. R., DePaoli, M., & Rabin, B. S. (1993). Exposure to physical and psychological Stressors elevates plasma interleukin 6: Relationship to the activation of the hypothalamic-pituitary-adrenal axis. Endocrinology, 133, 2523–2530.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers 1999

Authors and Affiliations

  • Andrew H. Miller
    • 1
  • Carmine M. Pariante
    • 1
  • Bradley D. Pearce
    • 1
  1. 1.Department of Psychiatry and Behavioral SciencesEmory University School of MedicineAtlanta

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