Endocrine and Immunological Responses to Acute Stress

  • F. Berkenbosch
  • C. J. Heijnen
  • G. Croiset
  • C. Revers
  • R. E. Ballieux
  • R. Binnekade
  • F. J. H. Tilders


Although the suggestion that the function of the immune system is regulated by the endocrine system, was postulated some time ago (see Selye, 1980; Besedovsky and Sorkin, 1977), the extent of this interaction is now becoming more obvious by many recent technological advances in the field of endocrinology and immunology. For instance, regulation of the immune response by the hypothalamo-pituitary gonadal axis has been proved to be of great importance (Grossman, 1984) and also growth hormone (Grossman and Roselle, 1983; Michael et al., 1980) prolactin (Bercze et al., 1981), glucocorticoids (Munck et al., 1984), as well as peripheral circulating catecholamines (Johnson et al., 1981; Del Rey et al., 1981) have been shown to have immunomodulatory capacities. Recent studies have presented evidence that lymphocytes possess binding sites for opiates such as morphine and its derivates (Wybran et al., 1979; Gungor et al., 1980; Lopker et al., 1980). The presence of these binding sites would indicate that opiates may be able to affect the immune system directly. In this light, the discovery of the existence of endogenous opiates such as the enkephalins and endorphins motivated many workers to study the role of these peptides on immune function. However, as in other areas of opioid peptide physiology, the effects of opioid peptides in immune regulation are complex and often paradoxical.


Acute Stress Corticotropin Release Factor Restraint Stress Primary Immune Response Intermediate Lobe 
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  1. Berezi, I., Nagy, E., Kovacks, K. and Horvath, E., 1981, Regulation of humoral immunity in rats by pituitary hormones, Acta Endocrinol., 98: 506.Google Scholar
  2. Berkenbosch, F., Tilders, F.J.H. and Vermes, I., 1983, Beta-adrenoceptor activation mediates stress-induced secretion of beta-endorphin and related peptides from intermediate but not anterior pituitary, Nature, 305: 237.PubMedCrossRefGoogle Scholar
  3. Berkenbosch, F., Vermes, E., Binnkade, R. and Tilders, F.J.H., 1981, Beta-adrenergic stimulation induces an increase of plasma levels of immunoreactive alpha-MSH, beta-endorphin, ACTH and corticosterone, Life Sci., 29: 2249.PubMedCrossRefGoogle Scholar
  4. Berkenbosch, F., Vermes, I. and Tilders, F.J.H., 1984, The beta adrenoceptor blocking drug propranolol prevents secretion of immunoreactive beta-endorphin and alpha-melanocyte stimuli, Endocrinology, 115: 1051.PubMedCrossRefGoogle Scholar
  5. Besedovsky, H. and Sorkin, E., 1977, Network of immunoneuroendocrine interactions, Clin. Exp. Immunol., 27: 1.PubMedGoogle Scholar
  6. Boyum, A., 1968, The isolation of lymphocytes with density gradients, Scand. J. Clin. Lab. Invest., suppl. 97: 77.Google Scholar
  7. Burbach, H.P.G., Loeber, J.G., Verhoef, J., Kloet, E.R. and Wied, D., 1979, Biotransformation of endorphins by a synaptosomal plasma membrane preparation of rat brain and by human serum, Biochem. Biophys. Res. Comm., 86: 1296.PubMedCrossRefGoogle Scholar
  8. Cote, T.E., Eskay, R.L., Frey, E.A., Grewe, C.W., Munemura, M., Stoof, J.C., Tsuruta, K. and Kebabian, J.W., 1982, Biochemical and physiological studies of the beta-adrenoceptors and the D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland: A review, Neuroendocrinol., 35: 217.CrossRefGoogle Scholar
  9. Rey, A., Besedovsky, H.O., Sorkin, E., Da Prada, M. and Arrenbrecht, S., 1981, Immunoregulation mediated by the sympathetic nervous system, II, Cel. Immun., 63: 329.CrossRefGoogle Scholar
  10. Eipper, R.A., and Mains, R.E., 1980, Structure and biosynthesis of pro-adrenocorticotropin/endorphin and related peptides, Endocrine Rev., 1: 1.CrossRefGoogle Scholar
  11. Gillies, G.E., Linton, E.A. and Lowry, P.J., 1982, Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin, Nature, 299: 355.PubMedCrossRefGoogle Scholar
  12. Grossman, C.J., 1984, Regulation of the immune system by sex steroids, Endocrine Rev., 5: 435.CrossRefGoogle Scholar
  13. Grossman, C.J. and Roselle, G.A., 1983, The interrelationship of the HPG-thymic axis and immune system regulation, J. Steroid Biochem., 19 (1B): 461.PubMedCrossRefGoogle Scholar
  14. Guillemin, R.T., Vargo. J., Rossier, J., Minick, S., Ling, M., Rivier, J., Vale and Bloom, F.E., 1977, Beta-endorphin and adrenocorticotropin are secreted concomitantly by the pituitary, Science, 197: 1367.Google Scholar
  15. Gungor, M., Genc, E., Sagduyu, H., Eroglu, L. and Koyunoglu, H., 1980, Effect of chronic administration of morphine in primary immune response in mice, Experientia, 36: 1309.PubMedCrossRefGoogle Scholar
  16. Heijnen, C.J., Uytdehaag, F., Gmelig-Meyling, F.J.J., and Ballieux, R.E., 1979, Localization of human antigen-specific helper and suppressor function in distinct T-cell subpopulations, Cellular Immmnol., 43: 282.CrossRefGoogle Scholar
  17. Heijnen, C.J., Croiset, G., Bevers, C., Veldhuis, H.D., de Wied, D. and Ballieux, R.E., 1985, Interactions between the central nervous system and the immune system. In: New concepts of regulation of autonomic, neuroendocrine and immune systems, H.C. Hendrie, Ed. Martinus Nijhoff, The Hague.Google Scholar
  18. Hofman, K. and Vajima, H., 1961, Studies on polypeptides XX: synthesis and corticotropin activity of a peptide amide corresponding to Nterminal tridecapeptide sequence of the corticotropins, J. Am. Chem. Soc. 83: 2289.CrossRefGoogle Scholar
  19. Hope, J., Lowry, P.J., 1981, Pro-opiomelanocortin: The ACTH/LPH common precursor molecule, Front. Horm. Res., 8: 44.Google Scholar
  20. Johnson, D.L., Ashmore, R.E., and Gordon, M.A., 1981, Effects of betaadrenergic agents on the murine lymphocyte response to mitogen stimulation, J. Immunopharmac., 3: 205.CrossRefGoogle Scholar
  21. Kvetnansky, R., Sun, C.E., Lake, C.R., Thoa, N., Torda, R. and Kopin, I.J., 1977, Effect of handling and forced immobilization on rat plasma levels of epinephrine, norepinephrine and dopamine-beta-hydroxylase, Endocrinology, 103: 1868.CrossRefGoogle Scholar
  22. Kvetnansky, R. Tilders, F.J.H., Van Zoest, I.D., Dobrakovova, M., Berkenbosch, F., Culman, J., Zeman, P. and Smelik, P.G., Sympathoadrenal activity does not potentiate ACTH secretion but facilitates beta-endorphin and alpha MSH secretion during immobilization stress, submitted.Google Scholar
  23. Linton, E.A., Tilders, F.J.H., Hodgkindon, S., Berkenbosch, F., Vernies, I. and Lowry, P.J., Stress-induced secretion of ACTH in rats is inhibited by administration of antisera to bovine corticotropin releasing factor and vasopressin, Endocrinology, in press.Google Scholar
  24. Lopker, A., Abood, L.G., Moss, W. and Lionetti, F.J., 1980, Stereoselective muscarinic acetylcholine and opiate receptors in human phagocytic leukocytes, Biochem. Pharmacol., 29: 1361.PubMedCrossRefGoogle Scholar
  25. Mains, R.E. and Eipper, R.A., 1981, Differences in posttranslational processing of beta-endorphin in rat anterior and intermediate pituitary, J. Biol. Chem., 256: 5683.PubMedGoogle Scholar
  26. Michael, S.D., Taguchi, O. and Nishizuka, Y., 1980, Effect of neonatal thymectomy on ovarian development and plasma LH, FSN, GH and PRL in the mouse, Biol. Reprod., 22: 343.PubMedGoogle Scholar
  27. Munck, A., Guyre, N.G. and Holbrook, N.G., 1984, Physiological functions of glucocorticoids in stress and their relation to pharmacological actions, Endocrine Rev., 5: 25.CrossRefGoogle Scholar
  28. Riley, V., 1981, Psychoneuroendocrine influences on immunocompetence and neoplasia, Science, 212: 1100.PubMedCrossRefGoogle Scholar
  29. Roberts, J.L., Chen, C.C., EBerwine, J.J., Eviner, M.J.A., Herbert, E. and Schachter, R.S., 1982, Glucocorticoid regulation of proopiomelanocortin gene expression in rodent pituitary, Rec. Prog. Horm. Res., 38: 227.PubMedGoogle Scholar
  30. Rossier, J., Grensch, E.D., Rivier, C., Ling, N., Guillemin, R. and Bloom, F.E., 1977, Footshock induces stress and increases beta-endorphin levels in blood but not in brain, Nature, 270: 618.PubMedCrossRefGoogle Scholar
  31. Seizinger, B.R. and Hollt, V., 1980, In vitro biosynthesis and Nacetylation of beta-endorphin in pars intermedia of the rat pituitary gland, Biochem. Biophys. Res. Comm., 96: 535.PubMedCrossRefGoogle Scholar
  32. Selye, H., 1980, ed. Selye’s guide to stress research, Vol. I., Van Nostrand Reinhold Co., New York.Google Scholar
  33. Smyth, D.G., Massey, D.E., Zakarian, S. and Finnie, M.D.A., 1979, Endorphins are stored in biologically active and inactive forms: isolation of alpha-N-acetyl peptides, Nature, 279: 252.PubMedCrossRefGoogle Scholar
  34. Tilders, F.J.H., Berkenbosch, F., and Smelik, P.G., 1982, Adrenergic mechanisms involved in the control of pituitary-adrenal activity in the rat: a beta-adrenergic stimulatory mechanism, Endocrinology, 110: 114.PubMedCrossRefGoogle Scholar
  35. Tilders, F.J.H., Berkenbosch, R. and Vermes, I., 1984, Stress-induced secretion of immunoreactive beta-endorphin in rats: Role of a betaadrenoceptor mechanism, In: Central and perpheral Endorphins: Basic and clinical effects, E.E. Muller and A.R. Ganazzani, éds., 115.Google Scholar
  36. Tilders, F.J.H., Berkenbosch, F., Vermes, I., Linton, E.A. and Smelik, P.G., 1981, Beta-adrenergic stimulation of the release of ACTH- and LPH-related peptides from the pars intermedia of the rat pituitary gland, Acta Endocrinol., 97: 343.PubMedGoogle Scholar
  37. Tilders, F.J.H., Schipper, J., Lowry, P.J. and Vermes, I., 1982, Effect of hypothalamic lesions on the presence of CRF-immunoreactive nerve terminals in themedian eminence and on the pituitary-adrenal response to stress, Reg. Pept., 5: 77.CrossRefGoogle Scholar
  38. Vale, W., Rivier, C., Brown, M., Spiess, J., Koob, G., Swanson, L., Bilezikjan, L., Bloom, F. and Rivier, J., 1983, Chemical and biological characterization of corticotropin releasing factor. Rec. Progr. Horm. Res., 39: 245.PubMedGoogle Scholar
  39. Vermes,I., Berkenbosch, F., Tilders, F.J.H. and Smelik, P.G., 1981, HYpothalamic deafferentation in the rat appears to discriminate between the anterior loöe and intermediate lobe response to stress, Neurosci. Lett., 27: 89.CrossRefGoogle Scholar
  40. Vos, J.G., Kreeftenberg, J.G., Kruijt, B.C., Kruizinga, W., and Stierenberg, P.A., 1980, The athymic rat. II Immunological characteristics, Clin. Immunol. Immunopathol., 15: 229.PubMedCrossRefGoogle Scholar
  41. Wybran, J., Appelboom, T., Famaey, J.P. and Govaerts, A., 1979, Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human blood T-lynphocytes, J. Immunol., 123: 1068.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • F. Berkenbosch
    • 1
  • C. J. Heijnen
    • 2
  • G. Croiset
    • 2
  • C. Revers
    • 2
  • R. E. Ballieux
    • 3
  • R. Binnekade
    • 1
  • F. J. H. Tilders
    • 1
  1. 1.Dept. Pharmacology, Medical FacultyFree UniversityAmsterdamThe Netherlands
  2. 2.Dept. ImmunologyUniversity Hospital for Children and YouthUtrechtThe Netherlands
  3. 3.Dept. Clinical ImmunologyUniversity HospitalUtrechtThe Netherlands

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