Abstract
Synthesized within the thymus, thymic peptides comprise a heterogenous family of polypeptidic hormones, that exerts important regulatory effects within the immune and the neuroendocrine systems. These peptides are themselves subject to control by hormones derived from the hypothalamo-pituitary axis and other endocrine glands. Regarding thymic hormonal function, thymulin production is upregulated by several hormones, including prolactin, growth hormone and thyroid hormones. Other aspects of thymic epithelial cell (’l’EC) physiology can also be modulated by hormones and neuropeptides, particularly cytokeratin expression, cell growth and production of extracellular matrix proteins, thus characterizing the pleiotropic action of these molecules on the thymic epithelium. Conversely, thymic derived peptides also regulate hormone release from the hypothalamo-pituitary axis and may act directly on target endocrine glands of this axis, modulating gonadal tissues. In addition, it has recently been shown that thymulin can modulate some peripheral nervous sensory functions, including those related to sensitivity to pain. According to the dose given, thymulin induces or reduces hyperalgesia related to both mechanical and thermal nociceptors and thus represents an important interface between the immune, endocrine and nervous systems.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Angioni, S., Iori, G., Cellini, M., Sardelli, S., Massolo, F., Petraglia, F. and Genazzani, A.R., Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children, Acta Endocrinol., 127 (1992) 237–241.
Bach, J.F., Thymulin (FTS-Zn), Clin. Immunol. & Allergy, 3 (1983) 133–156.
Badamchian, M., Spangelo, B.L., Damavandy, T., Mac Leod, R.M. and Goldstein, A.L., Complete amino acid sequence analysis of a peptide isolated from the thymus that enhances release of growth hormone and prolactin, Endocrinology, 128 (1991) 1580–1588.
Blalock, J.E., Production of peptide hormones and neurotransmitters by the immune system. In: J.E. Blalock (Eds.), Neuroimmunoendocrinology, 52, Karger, Basel, 1992, pp. 1–195.
Brown, O.A., Sosa, Y.E., Dardenne, M., Pleau, J.M. and Goya, R.G., Growth hormone-releasing activity of thymulin on pituitary somatotropes is age dependant, Neuroendocrinology, 69 (1999) 20–27.
Buckingham, J.C., Safieh, B., Singh, S. and Kendall, M.D., Interactions of corticotrophin and glucocorticoids in the control of thymulin release in the rat, Br. J. Pharmacol., 102 (1991) 15P.
Buckingham, J.C., Safieh-Garabedian, B., Singh, S., Arduino, L.A., Cover, P.O. and Kendall, M.D., Interactions between the hypothalamus-pituitary adrenal axis and the thymus in the rat: a role for corticotrophin in the control of thymulin release, J. Neuroendocrinol., 4 (1992) 295–301.
Dardenne, M. and Savino, W., Neuroendocrine control of thymic epithelium: Modulation of thymic endocrine function, cytokeratin expression, and cell proliferation by hormones and neuropeptides, Prog. Neuroendocrinimmunol, 3 (1990) 18–25.
Dardenne, M. and Savino, W., Control of thymus physiology by peptidic hormones and neuropeptides, Immunol. Today, 15 (1994) 518–523.
Dardenne, M., Savino, W., Gagnerault, M.C., Itoh, T. and Bach, J.F., Neuroendocrine control of thymic hormonal production. I. Prolctin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells, Endocrinology, 125 (1989) 3–12.
Fabris, N., Mocchegiani, E., Mariotti, S., Pacini, F. and Pinchera, A., Thyroid function modulates thymic endocrine activity, J. Clin. Endocrin. Metab., 75 (1986) 1251–1260.
Farah, J.M., Hall, N.R., Bishop, J. F., Goldstein, A.L. and O’Donohue, T.L., Thymosin fraction 5 stimulates secretion of immunoreactive beta-endorphin in mouse tumor cells, J. Neurosci. Res., 18 (1987) 140–146.
Goldstein, G. and Audhya, T., Thymopoietin to thymopentin experimental studies. In: E. Sundal (Ed.), Thymopentin experimental and clinical medicine, Karger, Basel, 1985, pp. 1–21.
Goya, R.G., Sosa, Y.E., Quigley, K.L., Gottschall, P.E., Goldstein, A.L. and Meites, J., Differential activity of thymosin peptides (thymosin fraction five) on plasma thyrotropin in female rats of different ages, Neuroendocrinology, 47 (1988) 379–383.
Goya, R.G., Takahashi, S., Quigley, K.L., Sosa, Y.E., Goldstein, A.L. and Meites, J., Immuneneuroendocrine interactions during aging: age-dependent thyrotropin-inhibiting activity of thymosin peptides, Mech. Ageing Dev., 41 (1987) 219–227.
Goya, R.G., Sosa, Y.E., Quigley, K.L., Reichhart, R. and Meites, J., Homeostatic thymus hormone stimulates corticosterone secretion in a dose-and age-dependent manner in rats, Neuroendocrinology, 51 (1990) 59–63.
Goya, R.G., Quigley, K.L., Takahashi, S., Reichhart, R. and Meites, J., Differential effect of homeostatic thymus hormone on plasma thyrotropin and growth hormone in young and old rats, Mech. Ageing Dev., 49 (1989) 119–128.
Hadley, A.J., Rantle, C.M. and Buckingham, J.C., Thymulin stimulates corticotrophin release and cyclic nucleotide formation in the rat anterior pituitary gland, NeuroImmunoModulation, 4 (1997) 62–69.
Hall, J.R., McGillis, J.P., Spangelo, B.L., Palaszynzki, E., Moody, T. and Goldstein, AL., Evidence for a neuroendocrine-thymus axis mediated by thymosin polypeptides. In: B. Serrou, C. Rosenfeld, J.C. Daniels J.P. Saunders (Eds.), Current Concepts in Human Immunology and Cancer Immunomodulation, 17, Elsevier, Amsterdam, 1982, pp. 653–660.
Healy, D.L., Hodgen, G.D., Schulte, H.M., Chrousos, G.P., Loriaux, D.L., Hall, N.R. and Goldstein, A.L., The thymus-adrenal connection: thymosin has corticotropin-releasing activity in primates, Science, 222 (1983) 1353–1355.
Iurato, M.P., Chiarenza, A., Barbera, N., Cantarella, G., Lempereur, L., Drago, F., Scapagini, U. and Bernardin, R., Thymic factors influence on behavior in rodents, Pharmacol. Biochem. Beh., 44 (1993) 665–671.
Janossy, G., Thomas, J.A, Bottum, F.L., Granzer, G., Pizzolo, G., Bradstock, K.F., Wong, L., Ganeshagun, K. and Hoffbrand, AB., The human thymic microenvironment: an immunohistologic study, J. Immunol., 125 (1980) 202–212.
Jenkinson, E.J., Van Ewijk, W. and Owen, J.J., Major histocompatibility complex antigen expression on the epithelium of developing thymus in normal and nude mice, J. Exp. Med., 153 (1981) 280–292.
Jennings, K.R. and Shien, H.M., The effects of synthetic thymopoietin on binding of alphabungarotoxin to rat neural membranes, Comp. Biochem. Physiol., 104 (1993) 411–413.
Le, P.T., Lazorich, S., Whichard, L.P., Yang, Y.C., Clarck, S.C., Haynes, B.F. and Singer, K.H., Human thymic epithelial cells produce IL-6, granulocyte-monocye CSF and leukemia inhibitory factor, J. Immunol., 145 (1990) 3310–3315.
Le, P.T., Tuck, D.T., Dinarello, C.A., Haynes, B.F. and Singer, K.H., Thymic epithelial cells produce interleukin 1, J. Immunol., 138 (1988) 2520–2525.
D. Gerber, H., Gerschpacher, H., Stocker, H. and Bolla, K., Treatment of active rheumatoid arthritis with slow intravenous injections of thymopentin. A double-blind placebo-controlled randomised study, Lancet, 1 (1985) 832–836.
Malaise, M.G., Hazee-Hagelstein, M.T., Reuter, A.M., Vrinds-Gevaert, Y., Goldstein, G. and Franchimont, P., Thymopoietin and thymopentin enhance the levels of ACTH, beta-endorphin and beta-lipotropin from rat pituitary cells in vitro, Acta Endocrinol., 115 (1987) 455–460.
Malaise, M.G., Hauwaert, C., Franchimont, P., Danneskiold-Samsoe, B., Bach-Andersen, R., Gross, Michael, S.D., Taguchi, O. and Nishizuka, Y., Effect of neonatal thymectomy on ovarian development and plasma LH, FSH, GH and PRL in the mouse, Biol. Reprod., 22 (1976) 343–350.
Michael, S.D., Taguchi, O. and Nishizuka, Y., Effect of neonatal thymectomy on ovarian development and plasma LH, FSH, GH, and PRL in the mouse, Biol. Reprod., 22 (1980) 343–350.
Milenkovic, L., Lyson, K., Aguila, M.C. and McCann, S.M., Effect of thymosin alpha 1 on hypothalamic hormone release, Neuroendocrinology, 56 (1992) 674–679.
Milenkovic, L. and McCann, S.M., Effects of thymosin alpha-1 on pituitary hormone release, Neuroendocrinology, 55 (1992) 14–19.
Mocchegiani, E., Amadio, L. and Fabris, N., Neuroendocrine-thymus interactions. I. In vitro modulation of thymic factor secretion by thyroid hormones, J. Endocrinol.Invest., 13 (1990) 139–147.
Mocchegiani, E., Paolucci, P., Balsamo, A., Cacciari, E. and Fabris, N., Influence of growth hormone on thymic endocrine activity in humans, Horm. Res., 33 (1990) 248–255.
Nishizuka, Y. and Sakakura, T., Thymus and reproduction: sex-linked dysgenesis of the gonad after neonatal thymectomy in mice, Science, (1969) 753–755.
Nonoyama, S., Nakayama, M., Shiohara, T. and Yata, J., Only dull CD3+ thymocytes bind to thymic epithelial cells. The binding is elicited by both CD2/LFA-3 and LFA-1/ICAM-1 interactions, Eur. J. Immunol., 19 (1989) 1631–1635.
Palaszynski, E.W., Moody, T.W., O’Donohue, T.L. and Goldstein, A.L., Thymosin al-like peptides: localization and biochemical characterization in the rat brain and pituitary gland, Peptides, 4 (1983) 463–467.
Pelletier, M., Montplaisir, S., Dardenne, M. and Bach, J.F., Thymic hormone activity and spontaneous auotimmunity in dwarf and their littermates, Immunology, 30 (1976) 783–788.
Pierpaoli, W., Kopp, H.G. and Bianchi, E., Interdependence of thymic and neuroendocrine functions in ogtogeny, Clin. Exp. Immunol., 24 (1976) 501–506.
Prepin, J., Fetal thymus and thymulin stimulate the in vitro proliferation of oogonia in the fetal rat ovary, C R Acad. Sci. [III], 313 (1991) 407–411.
Prepin, J., Fetal thymus and thymulin stimulate in vitro proliferation of gonocytes in the fetal testis in rats, C R Acad. Sci. [III], 316 (1993) 451–454.
Rebar, R.W., Morandini, I.C., Bernirschke, K. and Petze, J. E., Reduced gonadotropins in athymic mice:prevention by thymic transplantation, Endocrinology, 107 (1980) 2130–2132.
Rebar, R.W., Miyake, A., Low, T.L. and Goldstein, A.L., Thymosin stimulates secretion of luteinizing hormone-releasing factor, Science, 214 (1981) 669–671.
Rebar, R.W., Morandini, I.C., Petze, J.E. and Erickson, G.F., Hormonal basis of reproductive defects in athymic mice: gonadotropins and testosterone in males, Biol. Reprod., 27 (1982) 1267–1276.
Reichhart, R., Zeppezauer, M. and Jornvall, H., Preparations of hemeostatic thymus hormone consist predominantly of histones 2A and 2B and suggest additonal histone functions, Proc. Natl. Acad. Sci., 82 (1985) 4871–4875.
Ruitenberg, E.J. and Berkvens, J.M., The morphology of the endocrine system in congenitally athymic (nude) mice, J. Pathol., 121 (1977) 225–231.
Safieh, B., Venn, G.E., Ritter, M., Singh, S., Buckingham, J.C. and Kendall, M.D., Plasma thymulin concentations in cardiac patients: involvement with the hypothalamo-pituitary-adrenal axis, J. Physiol. (Paris), 438 (1991) 50p.
Safieh-Garabedian, B., Ahmed, K., Khamashta, M.A. and Hughes, G.R.V., Thymulin modulates cytokine release by peripheral blood mononuclear cells: a comparison between healthy volunteers and patients with systemic lupus erythematosus, Int. Arch Allergy Immunol., 101 (1993) 126–131.
Safieh-Garabedian, B., Jalakhian, R.H., Saadé, N.E., Haddad, J.J., Jabbur, S.J. and Kanaan, S.A., Thymulin reduces hyperalgesia induced by peripheral endotoxin injectin in rats and mice, Brain Res., 717 (1996) 179–183.
Safieh-Garabedian, B., Kanaan, S.A., Jalakhian, R.H., Poole, S., Jabbur, S.J. and Saadé, N.E., Hyperalgesia induced by low doses of thymulin injections: possible involvement of prostaglandin E2, J. Neuroimmunol., 73 (1997) 162–168.
Savino, W., Gagnerault, M.C., Bach, J.F. and Dardenne, M., Neuroendocrine control of thymic hormonal production. II. Stimulatory effects of endogenous opioids on thymulin production by cultured human and murine thymic epithelial cells, Life Sci., 46 (1990) 1687–1697.
Savino, W., Wolff, B., Aratan-Spire, S. and Dardenne, M., Thymic hormone containing cells. IV. Fluctuations in the thyroid hormone levels in vivo can modulate the secretion of thymulin by the epithelial cells of young mouse thymus, Clin. Exp. Immunol., 55 (1984) 629–635.
Spangelo, B.L., Hall, N.R., Dunn, A.J. and Goldstein, A.L., Thymosin fraction 5 stimulates the release of prolactin from cultured GH3 cells, Life Sci., 40 (1987) 283–288.
Spangelo, B.L., Judd, A.M., Ross, P.C., Login, I.S., Jarvis, W.D., Badamchian, M., Goldstein, A.L. and Mac Leod, R.M., Thymosin fraction 5 stimulates prolactin and growth hormone release from anterior pituitary, Endocrinology, 121 (1987) 2035–2043.
Su, Y., Ho, K.L., Dalakas, M.C. and Mutchnick, M.G., Localization of immunoreactive thymosin alpha 1 in astrocytes of normal human brain, Ann. Neurol., 26 (1989) 277–280.
Timsit, J., Savino, W., Safieh, B., Chanson, P., Gagnerault, M.C., Bach, J.F. and Dardenne, M., Effects of growth hormone and insulin-like growth factor 1 in thymic hormonal function in man, J. Clin. Endocrin. Metab., 75 (1992) 1251–1260.
Van Ewijk, W., T-cell differentiation is influenced by thymic microenvironmeuts, Ann. Rev. Immunol., 9 (1991) 591–615.
Van Ewijk, W., Ron, Y., Monaco, J., Kapplier, J., Marrack, P., Le Meur, H., Gerlinger, P., Durand, B., Benoist, C. and Mattis, D., Compartimentalization of MHC class II gene expression in transgenic mice, Cell, 53 (1988) 357–370.
Zaidi, S.A.A., Kendall, M.D., Gillham, B. and Jones, M.T., The release of LH from pituitaries perifused with thymic extracts, Thymus, 12 (1988) 253–264.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media New York
About this chapter
Cite this chapter
Dardenne, M., Safieh-Garabedian, B., Pleau, JM. (2000). Thymic Peptides: Transmitters Between the Neuroendocrine and the Immune System. In: Saadé, N.E., Apkarian, A.V., Jabbur, S.J. (eds) Pain and Neuroimmune Interactions. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4225-4_10
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4225-4_10
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6897-7
Online ISBN: 978-1-4615-4225-4
eBook Packages: Springer Book Archive