Advertisement

Neuroendocrine Involvement in Immune-Mediated Rheumatic Diseases

  • Maurizio CutoloEmail author
  • Amelia Chiara Trombetta
Living reference work entry
First Online:
Part of the Endocrinology book series (ENDOCR)

Abstract

In the present chapter, the evidences showing how neuro-endocrine-immune network integrates human organism functions in healthy and disease status will be summarized. Central and peripheral nervous systems in fact were demonstrated to present receptors for immune system products, like pro-inflammatory cytokines and growth factors. At the same time, immune system cells and peripheral tissues show receptors and are able produce and catabolize neurotransmitters and hormones. Consequently, in the main immune-mediated rheumatic diseases, several alterations of the interactions between nervous, endocrine, and immune systems have been described. At the same time, disease-modifying and biologic drugs have shown in several cases to determine the restoration of hormonal and nervous system activity while performing their main immune-modulating effect.

Keywords

Neuroendocrine immunology Rheumatoid arthritis Systemic lupus erytrhematosus Sjogren syndrome Polymialgia rheumatica Glucocorticoids Gender Sexual hormones 
This is a preview of subscription content, log in to check access.

References

  1. Abraham AD, Bug G. 3H-testosterone distribution and binding in rat thymus cells in vivo. Mol Cell Biochem. 1976;13:157–63.PubMedCrossRefGoogle Scholar
  2. Anaya JM, Liu GT, D’Souza E, Ogawa N, Luan X, Talal N. Primary Sjögren’s syndrome in the elderly: clinical and immunological characteristics. Lupus. 1999;8:20–3.CrossRefGoogle Scholar
  3. Arrenbrecht S. Specific binding of growth hormone to thymocytes. Nature. 1974;252:255–25.PubMedCrossRefGoogle Scholar
  4. Baerwald CG, Wahle M, Ulrichs T, Jonas D, von Bierbrauer A, von Wichert P, Burmester GR, Krause A, et al. Reduced catecholamine response of lymphocytes from patients with rheumatoid arthritis. Immunobiology. 1999;200:77–91.PubMedCrossRefGoogle Scholar
  5. Bailly S, Ferrua B, Fay M, Gougerot-Pocidalo MA. Differential regulation of IL 6, IL 1 a, IL 1 beta and TNF alpha production in LPS-stimulated human monocytes: role of cyclic AMP. Cytokine. 1990;2:205–10.PubMedCrossRefGoogle Scholar
  6. Besedovsky HO, del Rey A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev. 1996;17:64–102.PubMedCrossRefGoogle Scholar
  7. Besedovsky HO, del Rey AE, Sorkin E. Immune-neuroendocrine interactions. J Immunol. 1985;135:750–4.Google Scholar
  8. Boettger MK, Weber K, Grossmann D, Gajda M, Bauer R, Bär KJ, et al. Spinal tumor necrosis factor alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis: a role for spinal tumor necrosis factor alpha during induction and maintenance of peripheral inflammation. Arthritis Rheum. 2010;62:1308–18.PubMedCrossRefGoogle Scholar
  9. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405:458–62.PubMedCrossRefGoogle Scholar
  10. Bosmann M, Meta F, Ruemmler R, Haggadone MD, Sarma JV, Zetoune FS, et al. Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice. Am J Pathol. 2013;182:1124–30.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bourne HR, Lichtenstein LM, Melmon KL, Henney CS, Weinstein Y, Shearer GM. Modulation of inflammation and immunity by cyclic AMP. Receptors for vasoactive hormones and mediators of inflammation regulate many leukocyte functions. Science. 1974;184:19–28.PubMedCrossRefGoogle Scholar
  12. Bynoe MS, Grimaldi CM, Diamond B. Estrogen up-regulates Bcl-2 and blocks tolerance induction of naıve B cells. Proc Natl Acad Sci U S A. 2000;97:2703–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Capellino S, Cosentino M, Wolff C, Schmidt M, Grifka J, Straub RH. Catecholamine-producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target. Ann Rheum Dis. 2010;69:1853–60.PubMedCrossRefGoogle Scholar
  14. Carlsten H, Nilsson N, Jonsson R, Backman K, Holmdahl R, Tarkowski A. Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice 86. Cell Immunol. 1992;144:190–202.PubMedCrossRefGoogle Scholar
  15. Chabbi-Achengli Y, Coman T, Collet C, Callebert J, Corcelli M, Lin H, et al. Serotonin is involved in autoimmune arthritis through Th17 immunity and bone resorption. Am J Pathol. 2016;186:927–37.PubMedCrossRefGoogle Scholar
  16. Chang Y, Albright S, Lee F. Cytokines in the central nervous system: expression of macrophage colony stimulating factor and its receptor during development. J Neuroimmunol. 1994;52:9–17.PubMedCrossRefGoogle Scholar
  17. Chikanza IC, Grossman AB. Reciprocal interactions between the neuroendocrine and immune systems during inflammation. Rheum Dis Clin N Am. 2000;26:693–711.CrossRefGoogle Scholar
  18. Conde J, Scotece M, Abella V, López V, Pino J, Gómez-Reino JJ, et al. An update on leptin as immunomodulator. Expert Rev Clin Immunol. 2014;10:1165–70.PubMedCrossRefGoogle Scholar
  19. Crofford LJ, Sano H, Karalis K, Friedman TC, Epps HR, Remmers EF, et al. Corticotropin-releasing hormone in synovial fluids and tissues of patients with rheumatoid arthritis and osteoarthritis. J Immunol. 1993;151:1587–96.PubMedGoogle Scholar
  20. Cutolo M, Maestroni GJ. The melatonin-cytokine connection in rheumatoid arthritis. Ann Rheum Dis. 2005;64:1109–11.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Cutolo M, Straub RH. Polymyalgia rheumatica: evidence for a hypothalamic-pituitary-adrenal axis-driven disease. Clin Exp Rheumatol. 2000;18:655–8.PubMedGoogle Scholar
  22. Cutolo M, Wilder RL. Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases. Rheum Dis Clin N Am. 2000;26:825–39.CrossRefGoogle Scholar
  23. Cutolo M, Balleari E, Giusti M, Monachesi M, Accardo S. Sex hormone status of male patients with rheumatoid arthritis: evidence of low serum concentrations of testosterone at baseline and after human chorionic gonadotropin stimulation. Arthritis Rheum. 1988;31:1314–7.PubMedCrossRefGoogle Scholar
  24. Cutolo M, Kirkham BC, Sany BJ, Scott D, Brooks P, Forre O, et al. Loading/maintenance doses approach to neutralization of TNF by Lenercept (TNFR55-IgG1, Ro 45-2081) in patients with rheumatoid arthritis treated for 3months: results of double-blind placebo controlled phase II trial. Arthritis Rheum. 1996;39(Supplement):S243.Google Scholar
  25. Cutolo M, Foppiani L, Prete C, Ballarino P, Sulli A, Villaggio B, et al. Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocorticoids. J Rheumatol. 1999;26:282–8.PubMedGoogle Scholar
  26. Cutolo M, Sulli A, Pizzorni C, Craviotto C, Prete C, Foppiani L, et al. Cortisol, dehydroepiandrosterone sulfate, and androstenedione levels in patients with polymyalgia rheumatica during twelve months of glucocorticoid therapy. N Y Acad Sci. 2002;966:91–6.CrossRefGoogle Scholar
  27. Cutolo M, Capellino S, Montagna P, Villaggio B, Sulli A, Seriolo B, et al. New roles for estrogens in rheumatoid arthritis. Clin Exp Rheumatol. 2003a;21:687–90.PubMedGoogle Scholar
  28. Cutolo M, Sulli A, Pizzorni C, Craviotto C, Straub RH. Hypothalamic-pituitary-adrenocortical and gonadal functions in rheumatoid arthritis. Ann N Y Acad Sci. 2003b;992:107–17.PubMedCrossRefGoogle Scholar
  29. Cutolo M, Capellino S, Montagna P, Villaggio B, Sulli A, Seriolo B, et al. New roles for estrogens in rheumatoid arthritis. Clin Exp Rheumatol. 2003c;21:687–90.PubMedGoogle Scholar
  30. Cutolo M, Straub RH, Buttgereit F. Circadian rhythms of nocturnal hormones in rheumatoid arthritis: translation from bench to bedside. Ann Rheum Dis. 2008;67:905–8.PubMedCrossRefGoogle Scholar
  31. Cutolo M, Hopp M, Liebscher S, Dasgupta B, Buttgereit F. Modified-release prednisone for polymyalgia rheumatica: a multicentre, randomised, active-controlled, double-blind, parallel-group study. RMD Open. 2017;3:e000426.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Dailey MO, Schreurs J, Schulman H. Hormone receptors on cloned T lymphocytes. Increased responsiveness to histamine, prostaglandins and β-adrenergic agents as a late stage in T cell activation. J Immunol. 1988;140:2931–6.PubMedGoogle Scholar
  33. De Souza EB, Webster EL, Grigoriadis DE, Tracey DE. Corticotropin-releasing factor (CRF) and interleukin-1 (IL-1) receptors in the brain-pituitary-immune axis. Psychopharmacol Bull. 1989;25:299–305.PubMedGoogle Scholar
  34. Dekkers JC, Geenen R, Godaert GL, Glaudemans KA, Lafeber FP, van Doornen LJ, et al. Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis. J Rheumatol. 2001;28:1496–504.PubMedGoogle Scholar
  35. Dicou E, Perrot S, Menkes CJ, Masson C, Nerriere V. Nerve growth factor (NGF) autoantibodies and NGF in the synovial fluid: implications in spondylarthropathies. Autoimmunity. 1996;24:1–9.PubMedCrossRefGoogle Scholar
  36. Ernestam S, Hafstrom I, Werner S, Carlstrom K, Tengstrand B. Increased DHEAS levels in patients with rheumatoid arthritis after treatment with tumor necrosis factor antagonists: evidence for improved adrenal function. J Rheumatol. 2007;34:1451–8.PubMedGoogle Scholar
  37. Forrest CM, Mackay GM, Stoy N, Stone TW, Darlington LG. Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin. Br J Clin Pharmacol. 2007;64:517–26.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Galant SP, Remo RA. Beta-adrenergic inhibition of human T lymphocyte rosettes. J Immunol. 1975;114:512–3.PubMedGoogle Scholar
  39. Gillette S, Gillette R. Changes in thymic estrogen receptor expression following orchidectomy. Cell Immunol. 1979;42:194–6.PubMedCrossRefGoogle Scholar
  40. Gisler RH, Schenkel-Hulliger L. Hormonal regulation of the immune response. II. Influence of pituitary and adrenal activity on immune responsiveness in vitro. Cell Immunol. 1971;2:646–57.PubMedCrossRefGoogle Scholar
  41. Guirao X, Kumar A, Katz J, Smith M, Lin E, Keogh C, et al. Catecholamines increase monocyte TNF receptors and inhibit TNF through beta 2-adrenoreceptor activation. Am J Phys. 1997;273:E1203–8.Google Scholar
  42. Guo F, Yu J, Jae Jung H, Abruzzi KC, Luo W, Griffith LC, et al. Circadian neuron feedback controls the Drosophila sleep–activity profile. Nature. 2016;536:292–7.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hadden JW, Hadden EM, Middleton EJ. Lymphocyte blast transformation. Demonstration of adrenergic receptors in human peripheral lymphocytes. Cell Immunol. 1970;1:583–95.PubMedCrossRefGoogle Scholar
  44. Harbuz MS, Rees RG, Eckland D, Jessop DS, Brewerton D, Lightman SL. Paradoxical responses of hypothalamic corticotropin-releasing factor (CRF) messenger ribonucleic acid (mRNA) and CRF-41 peptide and adenohypophysial propiomelanocortin mRNA during chronic inflammatory stress. Endocrinology. 1992;130:1394–400.PubMedGoogle Scholar
  45. Härle P, Straub RH, Wiest R, Mayer A, Schölmerich J, Atzeni F, et al. Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems. Ann Rheum Dis. 2006;65:51–6.PubMedCrossRefGoogle Scholar
  46. Härle P, Pongratz G, Albrecht J, Tarner IH, Straub RH. An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells. Arthritis Rheum. 2008;58:2347–55.PubMedCrossRefGoogle Scholar
  47. Hazum E, Chang KJ, Cuatrecasas P. Specific nonopiate receptors for beta endorphins. Science. 1979;205:1033–5.PubMedCrossRefGoogle Scholar
  48. Helderman JH, Strom T. Specific insulin binding site on T and B lymphocytes as a marker of cell activation. Nature. 1978a;274:62–3.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Helderman JH, Strom T. Specific insulin binding site on T and B lymphocytes as a marker of cell activation. Nature. 1978b;274:62–3.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Hench PS. The ameliorating effect of pregnancy on chronic atrophic (infectious, rheumatoid) arthritis, fibrositis, and intermittent hydrarthrosis. Proc Staff Meet Mayo Clin. 1938;13:161–7.Google Scholar
  51. Herxheimer H, Rosa L. The protective effect of sympathicomimetic amines and of aminophylline in the anaphylactic microshock of the Guinea-pig. Br J Pharmacol Chemother. 1953;8:177–80.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Imrich R, Bosak V, Rovensky J. Polymyalgia rheumatica and temporal arteritis: the endocrine relations and the pathogenesis. Review Endocr Regul. 2006;40:83–9.PubMedGoogle Scholar
  53. Jara LJ, Medina G, Saavedra MA, Vera-Lastra O, Navarro C. Prolactin and autoimmunity. Clin Rev Allergy Immunol. 2011;40:50–9.PubMedCrossRefGoogle Scholar
  54. Jenei-Lanzl Z, Zwingenberg J, Lowin T, Anders S, Straub RH. Proinflammatory receptor switch from Gαs to Gαi signaling by β-arrestin-mediated PDE4 recruitment in mixed RA synovial cells. Brain Behav Immun. 2015;50:266–74.PubMedCrossRefGoogle Scholar
  55. Jiang H, Shen X, Chen Z, Liu F, Wang T, Xie Y, Ma C. Nociceptive neuronal fc-gamma receptor I is involved in IgG immune complex induced pain in the rat. Brain Behav Immun. 2017;62:351–61.PubMedCrossRefGoogle Scholar
  56. Johnson EO, Moutsopoulos HM. Neuroendocrine manifestations in Sjogren’s syndrome. Relation to the neurobiology of stress. Ann N Y Acad Sci. 2000;917:797–808.PubMedCrossRefGoogle Scholar
  57. Kassi E, Vlachoyiannopoulos PG, Kominakis A, Kiaris H, Moutsopoulos HM, Moutsatsou P. Estrogen receptor alpha gene polymorphism and systemic lupus erythematosus: a possible risk? Lupus. 2005;14:391–8.PubMedCrossRefGoogle Scholar
  58. Kinouchi K, Brown G, Pasternak G, Donner DB. Identification and characterization of receptors for tumor necrosis factor-alpha in the brain. Biochem Biophys Res Commun. 1991;18:1532–8.CrossRefGoogle Scholar
  59. Koller MD, Templ E, Riedl M, Clodi M, Wagner O, Smolen JS, et al. Pituitary function in patients with newly diagnosis untreated systemic lupus erythematosus. Ann Rheum Dis. 2004;63:1677–80.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Koopman FA, Chavan SS, Miljko S. Grazio S4 Sokolovic S5 Schuurman PR, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016;113:8284–9.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Lago R, Gómez R, Lago F, Gómez-Reino J, Gualillo O. Leptin beyond body weight regulation–current concepts concerning its role in immune function and inflammation. Cell Immunol. 2008;252:139–45.PubMedCrossRefGoogle Scholar
  62. Lahita RG. Sex and age in systemic lupus erythematosus. Systemic lupus erythematosus. New York: Wiley; 1986. p. 523–39.Google Scholar
  63. Lahita RG, Bradlow HL, Kunkel HG, Fishman J. Alterations of estrogen metabolism in systemic lupus erythematosus. Arthritis Rheum. 1979;22:1195–8.PubMedCrossRefGoogle Scholar
  64. Lahita RG, Bradlow HL, Ginzler E, Pang S, New M. Low plasma androgens in women with systemic lupus erythematosus. Arth Rheum. 1987;30:241–8.CrossRefGoogle Scholar
  65. Landmann RMA, Bittiger H, Biihler FR. High affinity beta-2-adrenergic receptors in mononuclear leucocytes: similar density in young and old normal subjects. Life Sci. 1981;29:1761–71.PubMedCrossRefGoogle Scholar
  66. Le Moine O, Stordeur P, Schandene L, Marchant A, De Groote D, Goldman M, et al. Adenosine enhances IL-10 secretion by human monocytes. J Immunol. 1996;156:4408–14.PubMedGoogle Scholar
  67. Lechner O, Hu Y, Jafarian-Tehrani M, Dietrich H, Schwarz S, Herold M, et al. Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in murine lupus. Brain Behav Immun. 1996;10:337–59.PubMedCrossRefGoogle Scholar
  68. Lechner O, Dietrich H, Oliveira dos Santos A, Wiegers GJ, Schwarz S, Harbutz M, et al. Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP- fas (Lpr) mice. J Autoimmun. 2000;14:325–33.PubMedCrossRefGoogle Scholar
  69. Lee YC, Raychaudhuri S, Cui J, De VI, Ding B, Alfredsson L, et al. The PRL- 1149G/T polymorphism and rheumatoid arthritis susceptibility. Arthritis Rheum. 2009;60:1250–4.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Levine YA, Koopman FA, Faltys M, Caravaca A, Bendele A, Zitnik R, et al. Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. PLoS One. 2014;9:e104530.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Lorton D, Bellinger DL. Molecular mechanisms underlying β-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells. Int J Mol Sci. 2015;16:5635–65.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Masi AT, Imrich R, Cutolo M. Hypothesis: can neuroendocrine immune (NEI) testing of individual RA patients guide benefits to harms ratio in glucocorticoid therapy? Arthritis Care Res (Hoboken). 2017;26  https://doi.org/10.1002/acr.23453. [Epub ahead of print]CrossRefGoogle Scholar
  73. Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab. 1993;77:1690–4.PubMedGoogle Scholar
  74. Matera L, Mori M, Geuna M, Buttiglieri S, Palestro G. Prolactin in auto-immunity and antitumor defence. J Neuroimmunol. 2000;109:47–55.PubMedCrossRefGoogle Scholar
  75. Miller LE, Justen HP, Scholmerich J, Straub RH. The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages. FASEB J. 2000;14:2097–107.PubMedCrossRefGoogle Scholar
  76. Miller LE, Grifka J, Scho Imerich J, Straub RH. Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritis. J Rheumatol. 2002;29:427–35.PubMedGoogle Scholar
  77. Ohmichi M, Hirota K, Koike K, Kurachi H, Ohtsuka S, Matsuzaki N, et al. Binding sites for interleukin-6 in the anterior pituitary gland. Neuroendocrinology. 1992;55:199–203.PubMedCrossRefGoogle Scholar
  78. O’Shaughnessy MC, Vetsika EK, Inglis JJ, Carleson J, Haigh R, Kidd BL, et al. The effect of substance P on nitric oxide release in a rheumatoid arthritis model. Inflamm Res. 2006;55:236–40.PubMedCrossRefGoogle Scholar
  79. Paolino S, Cutolo M, Pizzorni C. Glucocorticoid management in rheumatoid arthritis: morning or night low dose? Reumatologia. 2017;55:189–97.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Pereira da Silva JA, Carmo-Fonseca M. Peptide containing nerves in human synovium: immunohistochemical evidence for decreased innervation in rheumatoid arthritis. J Rheumatol. 1990;17:1592–9.PubMedGoogle Scholar
  81. Platzer C, Meisel C, Vogt K, Platzer M, Volk HD. Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int Immunol. 1995;7:517–23.PubMedCrossRefGoogle Scholar
  82. Pool AJ, Whipp BJ, Skasick AJ, Alavi A, Bland JM, Axford JS. Serum cortisol reduction and abnormal prolactin and CD4þ/CD8þ T-cell response as a result of controlled exercise in patients with rheumatoid arthritis and systemic lupus erythematosus despite unaltered muscle energetics. Rheumatology (Oxford). 2004;43:43–8.CrossRefGoogle Scholar
  83. Procaccini C, La Rocca C, Carbone F, De Rosa V, Galgani M, Matarese G. Leptin as immune mediator: interaction between neuroendocrine and immune system. Dev Comp Immunol. 2017;66:120–9.PubMedCrossRefGoogle Scholar
  84. Richman DP, Arnason BG. Nicotinic acetylcholine receptor: evidence for a functionally distinct receptor on human lymphocytes. Proc Natl Acad Sci U S A. 1979;76:4632–5.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Rivier C, Vale W. In the rat, interleukin-1 alpha acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. Endocrinology. 1989;124:2105–9.PubMedCrossRefGoogle Scholar
  86. Russell DH, Matrision L, Kibler R, Larson D, Poulps B, Magun B. Prolactin receptor on human lymphocytes and their modulation by cyclosporin. Biochem Biophys Res Commun. 1984;121:899–906.PubMedCrossRefGoogle Scholar
  87. Schaible HG. Nociceptive neurons detect cytokines in arthritis. Arthritis Res Ther. 2014;16:470.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Schmidt P, Holsboer F. Spengler D. beta(2)-adrenergic receptors potentiate glucocorticoid receptor transactivation via g protein betagamma-subunits and the phosphoinositide 3-kinase pathway. Mol Endocrinol. 2001;15:553–64.PubMedGoogle Scholar
  89. Schramm CM. Beta-adrenergic relaxation of rabbit tracheal smooth muscle: a receptor deficit that improves with corticosteroid administration. J Pharmacol Exp Ther. 2000;292:280–7.PubMedGoogle Scholar
  90. Severn A, Rapson NT, Hunter CA, Liew FY. Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J Immunol. 1992;148:3441–5.PubMedGoogle Scholar
  91. Shim GJ, Warner M, Kim HJ, Andersson S, Liu L, Ekman J, et al. Aromatase-deficient mice spontaneously develop a lym- phoproliferative autoimmune disease resembling Sjogren’s syndrome. Proc Natl Acad Sci U S A. 2004;101:12628–33.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Silva CA, Deen ME, Febronio MV, Oliveira SK, Terreri MT, Sacchetti SB, et al. Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea. Rheumatol Int. 2011;31:1037–43.PubMedCrossRefGoogle Scholar
  93. Smith LR, Brown SL, Blalock JE. Interleukin-2 induction of ACTH secretion: presence of an interleukin-2 receptor alpha-chain- like molecule on pituitary cells. J Neuroimmunol. 1989;21:249–54.PubMedCrossRefGoogle Scholar
  94. Spies CM, Schaumann DH, Berki T, Mayer K, Jakstadt M, Huscher D, et al. Membrane glucocorticoid receptors (mGCR) are down-regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1 independent expression pathway. Ann Rheum Dis. 2006;65:1139–46.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Srinivasan V, Spence DW, Trakht I, Pandi-Perumal SR, Cardinali DP, Maestroni GJ. Immunomodulation by melatonin: its significance for seasonally occurring diseases. Neuroimmunomodulation. 2008;15:93–101.PubMedCrossRefGoogle Scholar
  96. Stark K, Schmidt M, Rovensky J, Blazickova S, Lowin T, Straub RH. Influence of CYB5A gene variants on risk of rheumatoid arthritis and local endocrine function in the joint. Brain Behav Immun. 2013;29(Suppl):S12–3.CrossRefGoogle Scholar
  97. Sternberg EM, Hill JM, Chrousos GP, Kamilaris T, Listwak SJ, Gold PW, et al. Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci U S A. 1989;86:2374–8.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Straub RH. The complex role of estrogens in inflammation. Endocr Rev. 2007;28:521–74.CrossRefPubMedGoogle Scholar
  99. Straub RH, Cutolo M. Involvement of the hypothalamic—pituitary—adrenal/ gonadal axis and the peripheral nervous system in rheumatoid arthritis: viewpoint based on a systemic pathogenetic role. Arthritis Rheum. 2001;44:493–507.PubMedCrossRefGoogle Scholar
  100. Straub RH, Cutolo M. Glucocorticoids and chronic inflammation. Rheumatology (Oxford). 2016;55:ii6–ii14.CrossRefGoogle Scholar
  101. Straub RH, Konecna L, Hrach S, Rothe G, Kreutz M, Schölmerich J, et al. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab. 1998a;83:2012–7.PubMedCrossRefGoogle Scholar
  102. Straub RH, Konecna L, Hrach S, Rothe G, Kreutz M, Schölmerich J, et al. Serum DHEA and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab. 1998b;83:2012–7.PubMedCrossRefGoogle Scholar
  103. Straub RH, Glück T, Cutolo M, Georgi J, Helmke K, Schölmerich J, et al. The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica. Rheumatology (Oxford). 2000;39:624–31.CrossRefGoogle Scholar
  104. Straub RH, Günzler C, Miller LE, Cutolo M, Schölmerich J, Schill S. Anti-inflammatory cooperativity of corticosteroids and norepinephrine in rheumatoid arthritis synovial tissue in vivo and in vitro. FASEB J. 2002a;16:993–1000.PubMedCrossRefGoogle Scholar
  105. Straub RH, Paimela L, Peltomaa R, Schölmerich J, Leirisalo-Repo M. Inad- equately low serum levels of steroid hormones in relation to IL-6 and TNF in untreated patients with early rheumatoid arthritis and reactive arthritis. Arthritis Rheum. 2002b;46:654–62.PubMedCrossRefGoogle Scholar
  106. Straub RH, Pongratz G, Schölmerich J, Kees F, Schaible TF, Antoni C, et al. Long-term anti-tumor necrosis factor antibody therapy in rheumatoid arthritis patients sensitizes the pituitary gland and favors adrenal androgen secretion. Arthritis Rheum. 2003;48:1504–12.PubMedCrossRefGoogle Scholar
  107. Straub RH, Weidler C, Demmel B, Herrmann M, Kees F, Schmidt M, et al. Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rheumatoid arthritis and systemic lupus erythematosus. Rheum Dis. 2004;63:961–8.CrossRefGoogle Scholar
  108. Straub RH, Bijlsma JW, Masi A, Cutolo M. Role of neuroendocrine and neuroimmune mechanisms in chronic inflammatory rheumatic diseases–the 10-year update. Semin Arthritis Rheum. 2013;43:392–404.PubMedCrossRefGoogle Scholar
  109. Suehiro RM, Borba EF, Bonfa E, Okay TS, Cocuzza M, Soares PM, et al. Testicular Sertoli cell function in male systemic lupus erythematosus. Rheumatology (Oxford). 2008;47:1692–7.CrossRefGoogle Scholar
  110. Szabo G, Girouard L, Mandrekar P, Catalano D. Regulation of monocyte IL-12 production: augmentation by lymphocyte contact and acute ethanol treatment, inhibition by elevated intracellular cAMP. Int J Immunopharmacol. 1998;20:491–503.PubMedCrossRefGoogle Scholar
  111. Tai P, Wang J, Jin H, Song X, Yan J, Kang Y, et al. Induction of regulatory T cells by physiological level estrogen. J Cell Physiol. 2008;214:456–64.PubMedCrossRefGoogle Scholar
  112. Tengstrand B, Carlstrom K, Hafstrom I. Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism. Rheumatology (Oxford). 2002;41:285–9.CrossRefGoogle Scholar
  113. Tengstrand B, Carlstrom K, Hafstrom I. Gonadal hormones in men with rheumatoid arthritis—from onset through 2 years. J Rheumatol. 2009;36:887–92.PubMedCrossRefGoogle Scholar
  114. Torres-Ruiz J, Sulli A, Cutolo M, Air Travel SY. Circadian rhythms/hormones, and autoimmunity. Clin Rev Allergy Immunol. 2017;53:117–25.PubMedCrossRefGoogle Scholar
  115. Tsigos C, Papanicolaou DA, Defensor R, Mitsiadis CS, Kyrou I, Chrousos GP. Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology. 1997;66:54–62.PubMedCrossRefGoogle Scholar
  116. van der Goes MC, Bossema ER, Hartkamp A, Godaert GL, Jacobs JW, Kruize AA. Cortisol during the day in patients with systemic lupus erythematosus or primary Sjogren’s syndrome. J Rheumatol. 2011;38:285–8.PubMedCrossRefGoogle Scholar
  117. Verghese MW, McConnell RT, Strickland AB, Gooding RC, Stimpson SA, Yarnall DP, et al. Differential regulation of human monocyte-derived TNF alpha and IL-1 beta by type IV cAMP-phosphodiesterase (cAMP-PDE) inhibitors. J Pharmacol Exp Ther. 1995;272:1313–20.PubMedGoogle Scholar
  118. Walker SE, Jacobson JD. Roles of prolactin and gonadotropin-releasing hormone in rheumatic diseases. Rheum Dis Clin N Am. 2000a;26:713–36.CrossRefGoogle Scholar
  119. Walker SE, Jacobson JD. Roles of prolactin and gonadotropin-releasing hormone in rheumatic diseases. Rheum Dis Clin N Am. 2000b;26:713–36.CrossRefGoogle Scholar
  120. Webster EL, Barrientos RM, Contoreggi C, Isaac MG, Ligier S, Gabry KE, et al. Corticotropin releasing hormone (CRH) antagonist attenuates adjuvant induced arthritis: role of CRH in peripheral inflammation. J Rheumatol. 2002;29:1252–61.PubMedGoogle Scholar
  121. Weidler C, Holzer C, Harbuz M, Hofbauer R, Angele P, Schölmerich J, et al. Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium. Ann Rheum Dis. 2005;64:13–20.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Werb Z, Foley R, Munck A. Interaction of glucocorticoids with macrophages. Identification of glucocorticoid receptors in monocytes and macrophages. J Exp Med. 1978;147:1684–94.PubMedCrossRefGoogle Scholar
  123. Wybran J, Appelboom T, Famaey JP, Govaerts A. Suggestive evidence for morphin and methionine-enkephalin receptor-like structures on normal blood T lymphocytes. J Immunol. 1979;123:1068–70.PubMedGoogle Scholar
  124. Zietz B, Reber T, Oertel M, Gluck T, Scholmerich J, Straub RH. Altered function of the hypothalamic stress axes in patients with moderately active systemic lupus erythematosus. II. Dissociation between androstenedione, cortisol, or dehydroepiandrosterone and interleukin 6 or tumor necrosis factor. J Rheumatol. 2000;27:911–8.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Research Laboratory and Clinical Division of Rheumatology, Department of Internal MedicineUniversity of Genova, IRCCS San Martino Polyclinic HospitalGenovaItaly

Personalised recommendations

Cite entry