Advertisement

Neural Regulation of Inflammation: Pharmacological Mechanisms and Therapeutic Perspectives

  • Marco Cosentino
  • Franca Marino
Chapter

Abstract

During the past three decades, our knowledge about the close relationship and functional integration between the immune system and the nervous system hugely increased, and the relevance of the neuroimmune network in health and disease is now established, providing novel and unanticipated opportunities for the modulation of the immune response by means of conventional neural targets. Primary and secondary lymphoyd organs are extensively innervated by the autonomic nervous system, and cells of adaptive as well as innate immunity express receptors for neurotransmitters and neurohormones, including noradrenaline, adrenaline, acetylcholine and many others, which control critical immune functions. In addition, immune cells themselves may produce and utilize classical neurotransmitters, providing additional complexity to the network but also additional opportunities to develop novel immunomodulating strategies.

Neuroimmune pharmacology is a young but rapidly growing discipline, encompassing interdisciplinary research in pharmacology, immunology and neuroscience, offering original therapeutic approaches to investigate the neuroimmune network. The present chapter provides an overview of the main neurotransmitter-operated pathways affecting the immune system, as well as of their clinical and translational potential with regard to major diseases such as multiple sclerosis, cancer and rheumatoid arthritis.

Keywords

Neuroimmunology Neuroimmune Pharmacology Dopamine Noradrenaline Adrenaline Acetylcholine Glutamic acid Multiple sclerosis Cancer Rheumatoid arthritis Drug repurposing 

References

  1. 1.
    Felten DL, Felten SY (1988) Sympathetic noradrenergic innervation of immune organs. Brain Behav Immun 2:293–300PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES (2000) The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52:595–638PubMedPubMedCentralGoogle Scholar
  3. 3.
    De Potter WP, Partoens P, Schoups A, Llona I, Coen EP (1997) Noradrenergic neurons release both noradrenaline and neuropeptide Y from a single pool: the large dense cored vesicles. Synapse 25:44–55PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Bergquist J, Tarkowski A, Ekman R, Ewing A (1994) Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop. Proc Natl Acad Sci U S A 91:12912–12916PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Marino F, Cosentino M, Bombelli R, Ferrari M, Lecchini S, Frigo G (1999) Endogenous catecholamine synthesis, metabolism storage, and uptake in human peripheral blood mononuclear cells. Exp Hematol 27:489–495PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Cosentino M, Marino F, Bombelli R, Ferrari M, Lecchini S, Frigo G (1999) Endogenous catecholamine synthesis, metabolism, storage and uptake in human neutrophils. Life Sci 64:975–981PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Gordon MA, Cohen JJ, Wilson IB (1978) Muscarinic cholinergic receptors in murine lymphocytes: demonstration by direct binding. Proc Natl Acad Sci U S A 75:2902–2904PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Haddock AM, Patel KR, Alston WC, Kerr JW (1975) Response of lymphocyte guanyl cyclase to propranolol, noradrenaline, thymoxamine, and acetylcholine in extrinsic bronchial asthma. Br Med J 2:357–359PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Herr N, Bode C, Duerschmied D (2017) The effects of serotonin in immune cells. Front Cardiovasc Med 4:48PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Pittaluga A (2017) CCL5-glutamate cross-talk in astrocyte-neuron communication in multiple sclerosis. Front Immunol 8:1079. https://doi.org/10.3389/fimmu.2017.01079 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ganea D, Hooper KM, Kong W (2015) The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases. Acta Physiol (Oxf) 213:442–452CrossRefGoogle Scholar
  12. 12.
    Barragan A, Weidner JM, Jin Z, Korpi ER, Birnir B (2015) GABAergic signalling in the immune system. Acta Physiol (Oxf) 213:819–827CrossRefGoogle Scholar
  13. 13.
    Härle P, Straub RH (2005) Neuroendocrine-immune aspects of accelerated aging in rheumatoid arthritis. Curr Rheumatol Rep 7:389–394PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Shah N, Khurana S, Cheng RJP (2009) Muscarinic receptors and ligands in cancer. Am J Physiol Cell Physiol 296:C221–C232PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Calcagni E, Elenkov I (2006) Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. Ann N Y Acad Sci 1069:62–76PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    García JJ, del Carmen SM, De la Fuente M, Ortega E (2003) Noradrenaline and its end metabolite 3-methoxy-4-hydroxyphenylglycol inhibit lymphocyte chemotaxis: role of alpha- and beta-adrenoreceptors. Mol Cell Biochem 254:305–309PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP (2005) Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12:255–269PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Sanders VM (2006) Interdisciplinary research: noradrenergic regulation of adaptive immunity. Brain Behav Immun 20:1–8PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Maestroni GJ (2006) Sympathetic nervous system influence on the innate immune response. Ann N Y Acad Sci 1069:195–207PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Nance DM, Sanders VM (2007) Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 21:736–745PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Straznicky NE, Lambert GW, Lambert EA (2010) Neuroadrenergic dysfunction in obesity: an overview of the effects of weight loss. Curr Opin Lipidol 21:21–30PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Gomez-Marquez J, Paz-Paredes A (1971) Structural changes of the sympathetic ganglia in chronic arteriopathies. Angiologia 23:59–63PubMedPubMedCentralGoogle Scholar
  23. 23.
    Fronek K, Turner JD (1980) Combined effect of cholesterol feeding and sympathectomy on the lipid content in rabbit aortas. Atherosclerosis 37:521–528PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Ulloa L (2005) The vagus nerve and the nicotinic anti-inflammatory pathway. Nat Rev Drug Discov 4:673–684PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Moisse K, Strong MJ (2006) Innate immunity in amyotrophic lateral sclerosis. Biochim Biophys Acta 1762:1083–1093PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Ganor Y, Levite M (2014) The neurotransmitter glutamate and human T cells: glutamate receptors and glutamate-induced direct and potent effects on normal human T cells, cancerous human leukemia and lymphoma T cells, and autoimmune human T cells. J Neural Transm (Vienna) 121:983–1006CrossRefGoogle Scholar
  27. 27.
    Ossipov MH, Lai J, Malan TP, Porreca F (2000) Spinal and supraspinal mechanisms of neuropathic pain. Ann N Y Acad Sci 909:12–24PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Feldman RS, Meyer JS, Quenzer LF (1997) Catecholamines. In: Principles of neuropsychopharmacology. Sinauer Associates, Sunderland, pp 277–344Google Scholar
  29. 29.
    Sneader W (2005) Drug discovery: a history. Wiley, Chichester, pp 155–167CrossRefGoogle Scholar
  30. 30.
    Cosentino M, Marino F (2012). Nerve Driven immunity: noradrenaline and adrenaline. In Nerve-Driven immunity. Neurotransmitters and neuropetides in the immune system. Mia Levite Editor, Springer-Verlag WienCrossRefGoogle Scholar
  31. 31.
    Basu S, Dasgupta PS (2000) Dopamine, a neurotransmitter, influences the immune system. J Neuroimmunol 102:113–124PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Sarkar C, Basu B, Chakroborty D, Dasgupta PS, Basu S (2010) The immunoregulatory role of dopamine: an update. Brain Behav Immun 24:525–528PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Levite M (2012) Nerve-driven immunity neurotransmitters and neuropeptides in the immune system. In: Nerve-driven immunology. Springer, Vienna/New York, pp 1–45CrossRefGoogle Scholar
  34. 34.
    Cosentino M, Fietta AM, Ferrari M, Rasini E, Bombelli R, Carcano E, Saporiti F, Meloni F, Marino F, Lecchini S (2007) Human CD4+CD25+ regulatory T cells selectively express tyrosine hydroxylase and contain endogenous catecholamines subserving an autocrine/paracrine inhibitory functional loop. Blood 109:632–642PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Nakano K, Higashi T, Takagi R, Hashimoto K, Tanaka Y, Matsushita S (2009) Dopamine released by dendritic cells polarizes Th2 differentiation. Int Immunol 21:645–654PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78:189–225PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Cosentino M, Zaffaroni M, Ferrari M, Marino F, Bombelli R, Rasini E, Frigo G, Ghezzi A, Comi G, Lecchini S (2005) Interferon-gamma and interferon-beta affect endogenous catecholamines in human peripheral blood mononuclear cells: implications for multiple sclerosis. J Neuroimmunol 162:112–121PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Kustrimovic N, Rasini E, Legnaro M, Bombelli R, Aleksic I, Blandini F, Comi C, Mauri M, Minafra B, Riboldazzi G, Sanchez-Guajardo V, Marino F, Cosentino M (2016) Dopaminergic receptors on CD4+ T naive and memory lymphocytes correlate with motor impairment in patients with Parkinson’s disease. Sci Rep. https://doi.org/10.1038/srep33738
  39. 39.
    Marino F, Cosentino M (2016) Multiple sclerosis: repurposing dopaminergic drugs for MS--the evidence mounts. Nat Rev Neurol 12:191–192PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Capellino S, Cosentino M, Wolff C, Schmidt M, Grifka J, Straub RH (2010) Catecholamine- producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target. Ann Rheum Dis 69:1853–1860. https://doi.org/10.1136/ard.2009.119701 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Leite F, Lima M, Marino F, Cosentino M, Ribeiro L (2016) Dopaminergic receptors and tyrosine hydroxylase expression in peripheral blood mononuclear cells: a distinct pattern in central obesity. PLoS One 11(1):e0147483PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    McKenna F, McLaughlin PJ, Lewis BJ, Sibbring GC, Cummerson JA, Bowen-Jones D, Moots RJ (2002) Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils, eosinophils and NK cells: a flow cytometric study. J Neuroimmunol 132:34–40PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Pinoli M, Marino F, Cosentino M (2017) Dopaminergic regulation of innate immunity: a review. J Neuroimmune Pharmacol 12:602–623PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Yamazaki M, Matsuoka T, Yasui K, Komiyama A, Akabane T (1989) Dopamine inhibition of superoxide anion production by polymorphonuclear leukocytes. J Allergy Clin Immunol 83:967–972PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Wenisch C, Parschalk B, Weiss A, Zedwitz-Liebenstein K, Hahsler B, Wenisch H, Georgopoulos A, Graninger W (1996) High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production. Clin Diagn Lab Immunol 3:423–428PubMedPubMedCentralGoogle Scholar
  46. 46.
    Sookhai S, Wang JH, McCourt M, O'Connell D, Redmond HP (1999) Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism. Surgery 126:314–322PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Chen ML, Tsai TC, Wang LK, Lin YY, Tsai YM, Lee MC, Tsai FM (2012) Risperidone modulates the cytokine and chemokine release of dendritic cells and induces TNF-α-directed cell apoptosis in neutrophils. Int Immunopharmacol 12:197–204. https://doi.org/10.1016/j.intimp.2011.11.011 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Sookhai S, Wang JH, Winter D, Power C, Kirwan W, Redmond HP (2000) Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome. Shock 14:295–299PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Altenburg SP, Martins MA, Silva PM, Bozza PT, Tibiriçá EV, Cordeiro RS, Castro-Faria-Neto HC (1995) Systemic neutrophilia observed during anaphylactic shock in rats is inhibited by dopaminergic antagonists. Int Arch Allergy Immunol 108:33–38PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Pinoli M, Rasini E, Legnaro M, De Eguileor M, Pulze L, Cosentino M, Marino F (2016) Dopamine affects migration and morphology of human neutrophils through D1-like dopaminergic receptors. J Neuroimmune Pharmacol 11:S1-S2. https://doi.org/10.1007/s11481-016-9661-1
  51. 51.
    Cordano C, Pardini M, Cellerino M, Schenone A, Marino F, Cosentino M (2015) Levodopa- induced neutropenia. Parkinsonism Relat Disord 21:423–425. https://doi.org/10.1016/j.parkreldis.2015.02.002 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Podolec Z, Vetulani J, Bednarczyk B, Szczeklik A (1979) Central dopamine receptors regulate blood eosinophilia in the rat. Allergy 34:103–110PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Takkenberg JJ, Czer LS, Fishbein MC, Luthringer DJ, Quartel AW, Mirocha J, Queral CA, Blanche C, Trento A (2004) Eosinophilic myocarditis in patients awaiting heart transplantation. Crit Care Med 32:714–721PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Seol IW, Kuo NY, Kim KM (2004) Effects of dopaminergic drugs on the mast cell degranulation and nitric oxide generation in RAW 264.7 cells. Arch Pharm Res 27:94–98PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Coley JS, Calderon TM, Gaskill PJ, Eugenin EA, Berman JW (2015) Dopamine increases CD14+CD16+ monocyte migration and adhesion in the context of substance abuse and HIV neuropathogenesis. PLoS One 10(2):e0117450. https://doi.org/10.1371/journal.pone.0117450 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Calderon TM, Williams DW, Lopez L, Eugenin EA, Cheney L, Gaskill PJ, Veenstra M, Anastos K, Morgello S, Berman JW (2017) Dopamine increases CD14+CD16+ monocyte transmigration across the blood brain barrier: implications for substance abuse and HIV neuropathogenesis. J Neuroimmune Pharmacol 12:353–370PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Gaskill PJ, Yano HH, Kalpana GV, Javitch JA, Berman JW (2014) Dopamine receptor activation increases HIV entry into primary human macrophages. PLoS One. https://doi.org/10.1371/journal.pone.0108232
  58. 58.
    Gaskill PJ, Calderon TM, Luers AJ, Eugenin EA, Javitch JA, Berman JW (2009) Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine: a bridge between HIV-associated neurologic disorders and drug abuse. Am J Pathol 175:1148–1159PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Liang H, Wang X, Chen H, Song L, Ye L, Wang SH, Wang YJ, Zhou L, Ho WZ (2008) Methamphetamine enhances HIV infection of macrophages. Am J Pathol 172:1617–1624PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Yan Y, Jiang W, Liu L, Wang X, Ding C, Tian Z, Zhou R (2015) Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell 160:62–73PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Prado C, Contreras F, Gonzalez H, Diaz P, Elgueta D, Barrientos M, Herrada AA, Lladser A, Bernales S, Pacheco R (2012) Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity. J Immunol 188:3062–3070PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Nakano K, Higashi T, Hashimoto K, Takagi R, Tanaka Y, Matsushita S (2008) Antagonizing dopamine D1-like receptor inhibits Th17 cell differentiation: preventive and therapeutic effects on experimental autoimmune encephalomyelitis. Biochem Biophys Res Commun 373:286–291PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Zhao W, Huang Y, Liu Z, Cao BB, Peng YP, Qiu YH (2013) Dopamine receptors modulate cytotoxicity of natural killer cells via cAMP-PKA-CREB signaling pathway. PLoS One. https://doi.org/10.1371/journal.pone.0065860
  64. 64.
    Teunis MA, Heijnen CJ, Cools AR, Kavelaars A (2004) Reduced splenic natural killer cell activity in rats with a hyperreactive dopaminergic system. Psychoneuroendocrinol 29:1058–1064CrossRefGoogle Scholar
  65. 65.
    Theorell J, Gustavsson AL, Tesi B, Sigmundsson K, Ljunggren HG, Lundbäck T, Bryceson YT (2014) Immunomodulatory activity of commonly used drugs on Fc-receptor-mediated human natural killer cell activation. Cancer Immunol Immunother 63:627–641PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Vaarmann A, Ghandi S, Abramov AY (2010) Dopamine induces Ca2+ signaling in astrocytes through reactive oxygen species generated by monoamine oxidase. J Biol Chem 285:25018–25023PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Adluri RK, Singh AV, Skoyles J, Robins A, Parton J, Baker M, Mitchell IM (2010) The effect of fenoldopam and dopexamine on cytokine and endotoxin release following on-pump coronary artery bypass grafting: a prospective randomized double-blind trial. Heart Surg Forum 13:353–361CrossRefGoogle Scholar
  68. 68.
    Zaffaroni M, Marino F, Bombelli R, Rasini E, Monti M, Ferrari M, Ghezzi A, Comi G, Lecchini S, Cosentino M (2008) Therapy with interferon-beta modulates endogenous catecholamines in lymphocytes of patients with multiple sclerosis. Exp Neurol 214:315–321PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Capellino S, Cosentino M, Luini A, Bombelli R, Lowin T, Cutolo M, Marino F, Straub RH (2014) Increased expression of dopamine receptors in synovial fibroblasts from patients with rheumatoid arthritis. Arthritis Rheumatol 66:2685–2693PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Gong S, Li J, Ma L, Li K, Zhang L, Wang G, Liu Y, Ji X, Liu X, Chen P, Ouyang R, Zhang S, Zhou Z, Wang CY, Xiang X, Yang Y (2013) Blockade of dopamine D1-like receptor signalling protects mice against OVA-induced acute asthma by inhibiting B-cell activating transcription factor signalling and Th17 function. FEBS J 280:6262–6273PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Kouassi E, Li YS, Boukhris W, Millet I, Revillard JP (1988) Opposite effects of the catecholamines dopamine and norepinephrine on murine polyclonal B-cell activation. Immunopharmacology 16:125–137PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Watanabe Y, Nakayama T, Nagakubo D, Hieshima K, Jin Z, Katou F, Hashimoto K, Yoshie O (2006) Dopamine selectively induces migration and homing of naive CD8+ T cells via dopamine receptor D3. J Immunol 176:848–856PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Elkashef AM, Al-Barazi H, Venable D, Baker I, Hill J, Apud J, Wyatt RJ (2002) Dopamine effect on the mitochondria potential in B lymphocytes of schizophrenic patients and normal controls. Prog Neuro-Psychopharmacol Biol Psychiatry 26:145–148CrossRefGoogle Scholar
  74. 74.
    Tsao CW, Lin YS, Cheng JT (1997) Effect of dopamine on immune cell proliferation in mice. Life Sci 61:PL 361-71PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Cosentino M, Rasini E, Colombo C, Marino F, Blandini F, Ferrari M, Samuele A, Lecchini S, Nappi G, Frigo G (2004) Dopaminergic modulation of oxidative stress and apoptosis in human peripheral blood lymphocytes: evidence for a D1-like receptor-dependent protective effect. Free Radic Biol Med 36:1233–1240PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Melnikov M, Belousova O, Murugin V, Pashenkov М, Boyко A (2016) The role of dopamine in modulation of Th-17 immune response in multiple sclerosis. J Neuroimmunol 292:97–101PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Levite M, Chowers Y, Ganor Y, Besser M, Hershkovits R, Cahalon L (2001) Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates beta1 integrin function. Eur J Immunol 31:3504–3512PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Strell C, Sievers A, Bastian P, Lang K, Niggemann B, Zänker KS, Entschladen F (2009) Divergent effects of norepinephrine, dopamine and substance P on the activation, differentiation and effector functions of human cytotoxic T lymphocytes. BMC Immunol 10:62PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Besser MJ, Ganor Y, Levite M (2005) Dopamine by itself activates either D2, D3 or D1/D5 dopaminergic receptors in normal human T-cells and triggers the selective secretion of either IL-10, TNFalpha or both. J Neuroimmunol 169:161–171PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Ferreira TB, Barros PO, Teixeira B, Cassano T, Centurião N, Kasahara TM, Hygino J, Vasconcelos CC, Filho HA, Alvarenga R, Wing AC, Andrade RM, Andrade AF, Bento CA (2014) Dopamine favors expansion of glucocorticoid-resistant IL-17-producing T cells in multiple sclerosis. Brain Behav Immun 41:182–190PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Sarkar C, Das S, Chakroborty D, Chowdhury UR, Basu B, Dasgupta PS, Basu S (2006) Cutting edge: stimulation of dopamine D4 receptors induce T cell quiescence by up-regulating Kruppel- like factor-2 expression through inhibition of ERK1/ERK2 phosphorylation. J Immunol 177:7525–7529PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Huang Y, Chen CC, Wang TT, Qiu YH, Peng YP (2016) Dopamine receptors modulate T lymphocytes via inhibition of cAMP-CREB signaling pathway. Neuro Endocrinol Lett 37:491–500PubMedPubMedCentralGoogle Scholar
  83. 83.
    Zhu H, Lemos H, Bhatt B, Islam BN, Singh A, Gurav A, Huang L, Browning DD, Mellor A, Fulzele S, Singh N (2017) Carbidopa, a drug in use for management of Parkinson disease inhibits T cell activation and autoimmunity. PLoS One 12(9):e0183484PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Franz D, Contreras F, González H, Prado C, Elgueta D, Figueroa C, Pacheco R (2015) Dopamine receptors D3 and D5 regulate CD4(+)T-cell activation and differentiation by modulating ERK activation and cAMP production. J Neuroimmunol 284:18–29PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Scanzano A, Cosentino M (2015) Adrenergic regulation of innate immunity: a review. Front Pharmacol. https://doi.org/10.3389/fphar.2015.00171
  86. 86.
    Ahlquist RP (1948) A study of the adrenotropic receptors. Am J Phys 153:586–600Google Scholar
  87. 87.
    Bylund DB, Eikenberg DC, Hieble JP, Langer SZ, Lefkowitz RJ, Minneman KP, Molinoff PB, Ruffolo RR Jr, Trendelenburg U (1994) International Union of Pharmacology nomenclature of adrenoceptors. Pharmacol Rev 46:121–136PubMedPubMedCentralGoogle Scholar
  88. 88.
    Gauthier C, Tavernier G, Charpentier F, Langin D, Lemarec H (1996) Functional beta (3)- adrenoceptor in the human heart. J Clin Invest 98:556–562PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Harms HH, Zaagsma J, Van der Wal B. (1974) β-Adrenoceptor studies. III. On the β- adrenoceptors in rat adipose tissue. Eur J Pharmacol 25:87–91Google Scholar
  90. 90.
    Dessy C, Balligand JL (2010) Beta3-adrenergic receptors in cardiac and vascular tissues emerging concepts and therapeutic perspectives. Adv Pharmacol 59:135–163PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Arch S, Kaumann AJ (1993) Beta 3 and atypical beta-adrenoceptors. Med Res Rev 13:663–729PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Williams JM, Peterson RG, Shea PA, Schmedtje JF, Bauer DC, Felten DL (1981) Sympathetic innervation of murine thymus and spleen: evidence for a functional link between the nervous and immune systems. Brain Res Bull 6:83–94PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Elenkov IJ, Vizi ES (1991) Presynaptic modulation of release of noradrenaline from the sympathetic nerve terminals in the rat spleen. Neuropharmacology 30(12A):1319–1324PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Kohm AP, Sanders VM (2000) Norepinephrine: a messenger from the brain to the immune system. Immunol Today 21:539–542PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Bellinger DL, Lorton D, Felten SY, Felten DL (1992) Innervation of lymphoid organs and implications in development, aging, and autoimmunity. Int J Immunopharmacol 14:329–344PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Friedman EM, Irwin MR (1997) Modulation of immune cell function by the autonomic nervous system. Pharmacol Ther 74:27–38PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Straub RH, Wiest R, Strauch UG, Harle P, Scholmerich J (2006) The role of the sympathetic nervous system in intestinal inflammation. Gut 55:1640–1649PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Marino F, Cosentino M (2013) Adrenergic modulation of immune cells: an update. Amino Acids 45:55–71PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Kenney MJ, Ganta CK (2014) Autonomic nervous system and immune system interactions. Compr Physiol 4:1177–1200PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Nielson CP (1987) Beta-adrenergic modulation of the polymorphonuclear leukocyte respiratory burst is dependent upon the mechanism of cell activation. J Immunol 139:2392–2397PubMedPubMedCentralGoogle Scholar
  101. 101.
    Brunskole Hummel I, Reinartz MT, Kälble S, Burhenne H, Schwede F, Buschauer A, Seifert R (2013) Dissociations in the effects of β2-adrenergic receptor agonists on cAMP formation and superoxide production in human neutrophils: support for the concept of functional selectivity. PLoS One 8:e64556. https://doi.org/10.1371/journal.pone.0064556 CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Scanzano A, Schembri L, Rasini E, Luini A, Dallatorre J, Legnaro M, Bombelli R, Congiu T, Cosentino M, Marino F (2015) Adrenergic modulation of migration, CD11b and CD18 expression, ROS and interleukin-8 production by human polymorphonuclear leukocytes. Inflamm Res 64:127–135PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Wahle M, Greulich T, Baerwald CG, Häntzschel H, Kaufmann A (2005) Influence of catecholamines on cytokine production and expression of adhesion molecules of human neutrophils in vitro. Immunobiology 210:43–52PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Trabold B, Gruber M, Fröhlich D (2007) Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines. Scand Cardiovasc J 41:59–64PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Koch-Weser J (1968) Beta adrenergic blockade and circulating eosinophils. Arch Intern Med 121:255–258PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Munoz NM, Vita AJ, Neeley SP, McAllister K, Spaethe SM, White SR, Leff AR (1994) Beta adrenergic modulation of formyl-methionine-leucine-phenylalanine-stimulated secretion of eosinophil peroxidase and leukotriene C4. J Pharmacol Exp Ther 268:139–143PubMedPubMedCentralGoogle Scholar
  107. 107.
    Chong LK, Chess-Williams R, Peachell PT (2002) Pharmacological characterisation of the beta-adrenoceptor expressed by human lung mast cells. Eur J Pharmacol 437:1–7PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Wang XS, Lau HY (2006) Beta-adrenoceptor-mediated inhibition of mediator release from human peripheral blood-derived mast cells. Clin Exp Pharmacol Physiol 33:746–750PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Schopf RE, Lemmel EM (1983) Control of the production of oxygen intermediates of human polymorphonuclear leukocytes and monocytes by beta-adrenergic receptors. J Immunopharmacol 5:203–216PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Guirao X, Kumar A, Katz J, Smith M, Lin E, Keogh C, Calvano SE, Lowry SF (1997) Catecholamines increase monocyte TNF receptors and inhibit TNF through beta 2-adrenoreceptor activation. Am J Phys 273:E1203–E1208Google Scholar
  111. 111.
    Borda ES, Tenenbaum A, Sales ME, Rumi L, Sterin-Borda L (1998) Role of arachidonic acid metabolites in the action of a beta adrenergic agonist on human monocyte phagocytosis. Prostaglandins Leukot Essent Fatty Acids 58:85–90PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Prösch S, Wendt CE, Reinke P, Priemer C, Oppert M, Krüger DH, Volk HD, Döcke WD (2000) A novel link between stress and human cytomegalovirus (HCMV) infection: sympathetic hyperactivity stimulates HCMV activation. Virology 272:357–365PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Sarigianni M, Bekiari E, Tsapas A, Konstantinidis D, Kaloyianni M, Koliakos G, Paletas K (2011) Effect of epinephrine and insulin resistance on human monocytes obtained from lean and obese healthy participants: a pilot study. Angiology 62:38–45PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Paul-Eugène N, Kolb JP, Abadie A, Gordon J, Delespesse G, Sarfati M, Mencia-Huerta JM, Braquet P, Dugas B (1992) Ligation of CD23 triggers cAMP generation and release of inflammatory mediators in human monocytes. J Immunol 149:3066–3071Google Scholar
  115. 115.
    Paul- Eugène N, Kolb JP, Calenda A, Gordon J, Kikutani H, Kishimoto T, Mencia-Huerta JM, Braquet P, Dugas B (1993) Functional interaction between beta 2-adrenoceptor agonists and interleukin-4 in the regulation of CD23 expression and release and IgE production in human. Mol Immunol 30:157–164PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Paul-Eugène N, Kolb JP, Damais C, Abadie A, Mencia-Huerta JM, Braquet P, Bousquet J, Dugas B (1994) Beta 2-adrenoceptor agonists regulate the IL-4-induced phenotypical changes and IgE-dependent functions in normal human monocytes. J Leukoc Biol 55:313–320PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Kavelaars A, van de Pol M, Zijlstra J, Heijnen CJ (1997) Beta 2-adrenergic activation enhances interleukin-8 production by human monocytes. J Neuroimmunol 77:211–216PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Rainer TH, Lam N, Cocks RA (1999) Adrenaline upregulates monocyte L-selectin in vitro. Resuscitation 43:47–55PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Speidl WS, Toller WG, Kaun C, Weiss TW, Pfaffenberger S, Kastl SP, Furnkranz A, Maurer G, Huber K, Metzler H, Wojta J (2004) Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability. FASEB J 18:603–605PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Grisanti LA, Woster AP, Dahlman J, Sauter ER, Combs CK, Porter JE (2011) {alpha}1- adrenergic receptors positively regulate toll-like receptor cytokine production from human monocytes and macrophages. J Pharmacol Exp Ther 338:648–657PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Armaiz-Pena GN, Gonzalez-Villasana V, Nagaraja AS, Rodriguez-Aguayo C, Sadaoui NC, Stone RL, Matsuo K, Dalton HJ, Previs RA, Jennings NB, Dorniak P, Hansen JM, Arevalo JM, Cole SW, Lutgendorf SK, Sood AK, Lopez-Berestein G (2015) Adrenergic regulation of monocyte chemotactic protein 1 leads to enhanced macrophage recruitment and ovarian carcinoma growth. Oncotarget 6:4266–4273PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Panina-Bordignon P, Mazzeo D, Lucia PD, D’Ambrosio D, Lang R, Fabbri L, Self C, Sinigaglia F (1997) Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12. J Clin Invest 100:1513–1519PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Goyarts E, Matsui M, Mammone T, Bender AM, Wagner JA, Maes D, Granstein RD (2008) Norepinephrine modulates human dendritic cell activation by altering cytokine release. Exp Dermatol 17:188–196PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Yang H, Du RZ, Qiu JP, Tang YQ, Chen SC (2013) Bisoprolol reverses epinephrine- mediated inhibition of cell emigration through increases in the expression of β-arrestin 2 and CCR7 and PI3K phosphorylation, in dendritic cells loaded with cholesterol. Thromb Res 131:230–237PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Nijhuis LE, Olivier BJ, Dhawan S, Hilbers FW, Boon L, Wolkers MC, Samsom JN, de Jonge WJ (2014) Adrenergic β2 receptor activation stimulates anti-inflammatory properties of dendritic cells in vitro. PLoS One 9:e85086. https://doi.org/10.1371/journal.pone.0085086 CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Takamoto T, Hori Y, Koga Y, Toshima H, Hara A, Yokoyama MM (1991) Norepinephrine inhibits human natural killer cell activity in vitro. Int J Neurosci 58:127–131PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Benschop RJ, Schedlowski M, Wienecke H, Jacobs R, Schmidt RE (1997) Adrenergic control of natural killer cell circulation and adhesion. Brain Behav Immun 11:321–332PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Schedlowski M, Hosch W, Oberbeck R, Benschop RJ, Jacobs R, Raab HR, Schmidt RE (1996) Catecholamines modulate human NK cell circulation and function via spleen-independent beta 2-adrenergic mechanisms. J Immunol 156:93–99PubMedPubMedCentralGoogle Scholar
  129. 129.
    Lappin D, Whaley K (1982) Adrenergic receptors on monocytes modulate complement component synthesis. Clin Exp Immunol 47:606–612PubMedPubMedCentralGoogle Scholar
  130. 130.
    Gross CA, Bowler RP, Green RM, Weinberger AR, Schnell C, Chu HW (2010) Beta2- agonists promote host defense against bacterial infection in primary human bronchial epithelial cells. BMC 10:30. https://doi.org/10.1186/1471-2466-10-30 CrossRefGoogle Scholar
  131. 131.
    Riepl B, Grässel S, Wiest R, Fleck M, Straub RH (2010) Tumor necrosis factor and norepinephrine lower the levels of human neutrophil peptides 1-3 secretion by mixed synovial tissue cultures in osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 12:R110PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Cosentino M, Marino F, Bombelli R, Ferrari M, Rasini E, Lecchini S, Frigo G (2002) Stimulation with phytohaemagglutinin induces the synthesis of catecholamines in human peripheral blood mononuclear cells: role of protein kinase C and contribution of intracellular calcium. J Neuroimmunol 125:125–133PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Deo SH, Jenkins NT, Padilla J, Parrish AR, Fadel PJ (2013) Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol 305:R1124–R1132PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Takahashi HK, Morichika T, Iwagaki H, Yoshino T, Tamura R, Saito S, Mori S, Akagi T, Tanaka N, Nishibori M (2003) Effect of beta 2-adrenergic receptor stimulation on interleukin-18- induced intercellular adhesion molecule-1 expression and cytokine production. J Pharmacol Exp Ther 304:634–642PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Dale H (1914) The action of certain esters and ethers of choline and their relation to muscarine. J Pharmacol 6:147–160Google Scholar
  136. 136.
    Witzemann V, Brenner HR, Sakmann B (1991) Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses. J Cell Biol 114:125–141PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Orr-Urtreger A, Göldner FM, Saeki M, Lorenzo I, Goldberg L, De Biasi M, Dani JA, Patrick JW, Beaudet AL (1997) Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci 17:9165–9171PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Hellström-Lindahl E, Nordberg A (1996) Muscarinic receptor subtypes in subpopulations of human blood mononuclear cells as analyzed by RT-PCR technique. J Neuroimmunol 68:139–144PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Sato KZ, Fujii T, Watanabe Y, Yamada S, Ando T, Kazuko F, Kawashima K (1999) Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines. Neurosci Lett 266:17–20PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Wessler I, Reinheimer T, Klapproth H, Schneider FJ, Racké K, Hammer R (1997) Mammalian glial cells in culture synthesize acetylcholine. Naunyn Schmiedeberg's Arch Pharmacol 356:694–697CrossRefGoogle Scholar
  141. 141.
    Egea J, Buendia I, Parada E, Navarro E, Leon R, Lopez MG (2015) Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection. Biochem Pharmacol 97:463–472PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Kalkman HO, Feuerbach D (2016) Modulatory effects of alpha7 nAChRs on the immune system and its relevance for CNS disorders. Cell Mol Life Sci 73:2511–2530PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Shytle RD, Mori T, Townsend K, Vendrame M, Sun N, Zeng J, Ehrhart J, Silver AA, Sanberg PR, Tan J (2004) Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem 89:337–343PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Hiemke C, Stolp M, Reuss S, Wevers A, Reinhardt S, Maelicke A, Schlegel S, Schroder H (1996) Expression of alpha subunit genes of nicotinic acetylcholine receptors in human lymphocytes. Neurosci Lett 214:171–174PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    De Rosa MJ, Esandi Mdel C, Garelli A, Rayes D, Bouzat C (2005) Relationship between alpha 7 nAChR and apoptosis in human lymphocytes. J Neuroimmunol 160:154–161PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Kawashima K, Fujii T (2004) Expression of non-neuronal acetylcholine in lymphocytes and its contribution to the regulation of immune function. Front Biosci 9:2063–2085PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Kawashima K, Fujii T (2003) The lymphocytic cholinergic system and its contribution to the regulation of immune activity. Life Sci 74:675–696PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Kawashima K, Fujii T (2000) Extraneuronal cholinergic system in lymphocytes. Pharmacol Ther 86:29–48PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Shi FD, Piao WH, Kuo YP, Campagnolo DI, Vollmer TL, Lukas RJ (2009) Nicotinic attenuation of central nervous system inflammation and autoimmunity. J Immunol 182:1730–1739PubMedCrossRefPubMedCentralGoogle Scholar
  151. 151.
    Han B, Li X, Hao J (2017) The cholinergic anti-inflammatory pathway: An innovative treatment strategy for neurological diseases. Neurosci Biobehav Rev 77:358–368PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    Bernik TR, Friedman SG, Ochani M, DiRaimo R, Ulloa L, Yang H, Sudan S, Czura CJ, Ivanova SM, Tracey KJ (2002) Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 195:781–788PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Aicher C, Heeschen M, Mohaupt JP, Cooke AM, Zeiher S, Dimmeler S (2003) Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Circulation 107:604–611PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Totti N, McCusker KT, Campbell EJ, Griffin GL, Senior RM (1984) Nicotine is chemotactic for neutrophils and enhances neutrophil responsiveness to chemotactic peptides. Science 223:169–171PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Geng Y, Savage SM, Johnson LJ, Seagrave J, Sopori ML (1995) Effects of nicotine on the immune response. I. Chronic exposure to nicotine impairs antigen receptor-mediated signal transduction in lymphocytes. Toxicol Appl Pharmacol 135:268–278PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    Hamano R, Takahashi HK, Iwagaki H, Yoshino T, Nishibori M, Tanaka N (2006) Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes. Shock 26:358–364PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Sugano N, Shimada K, Ito K, Murai S (1998) Nicotine inhibits the production of inflammatory mediators in U937 cells through modulation of nuclear factor-kappaB activation. Biochem Biophys Res Commun 252:25–28PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Padilla A, Keating P, Hartmann JX, Marí F (2017) Effects of α-conotoxin ImI on TNF-α, IL-8 and TGF-β expression by human macrophage-like cells derived from THP-1 pre-monocytic leukemic cells. Sci Rep 7:12742PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Fujii T, Mashimo M, Moriwaki Y, Misawa H, Ono S, Horiguchi K, Kawashima K (2017) Expression and function of the cholinergic system in immune cells. Front Immunol 8:1085. https://doi.org/10.3389/fimmu.2017.01085 CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Ma C, Liu Y, Neumann S, Gao X (2017) Nicotine from cigarette smoking and diet and Parkinson disease: a review. Transl Neurodegener 6:18PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Di Bari M, Reale M, Di Nicola M, Orlando V, Galizia S, Porfilio I, Costantini E, D’Angelo C, Ruggieri S, Biagioni S, Gasperini C, Tata AM. (2016) Dysregulated homeostasis of acetylcholine levels in immune cells of RR-multiple sclerosis patients. Int J Mol Sci 17(12). pii: E2009Google Scholar
  162. 162.
    Valdés-Ferrer SI, Crispín JC, Belaunzarán-Zamudio PF, Rodríguez-Osorio CA, Cacho-Díaz B, Alcocer-Varela J, Cantú-Brito C, Sierra-Madero J (2017) Add-on pyridostigmine enhances CD4+ T-cell recovery in HIV-1-infected immunological non-responders: a proof-of-concept study. Front Immunol 8:1301PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Hayashi T (1956) Chemical physiology of excitation in muscle and nerve. Nakayama- Shoten, TokyoGoogle Scholar
  164. 164.
    Van Harreveld A (1959) Compounds in brain extracts causing spreading depression of cerebral cortical activity and contraction of crustacean muscle. J Neurochem 3:300–315CrossRefGoogle Scholar
  165. 165.
    Das S, Sasaki YF, Rothe T, Premkumar LS, Takasu M, Crandall JE, Dikkes P, Conner DA, Rayudu PV, Cheung W, Chen HS, Lipton SA, Nakanishi N (1998) Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 393:377–381PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, Shin Y, Cui J, Tu S, Sevarino KA, Nakanishi N, Tong G, Lipton SA, Zhang D (2002) Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415:793–798PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Ganor Y, Levite M (2012) Glutamate in the immune system: glutamate receptors in immune cells, potent effects, endogenous production and involvement in disease. In: Nerve-drive immunity. Mia Levite Editor, Spriger, pp 121–159CrossRefGoogle Scholar
  168. 168.
    Rosenmund C, Stern-Bach Y, Stevens CF (1998) The tetrameric structure of a glutamate receptor channel. Science 280:1596–1599PubMedCrossRefPubMedCentralGoogle Scholar
  169. 169.
    Armstrong N, Sun Y, Chen GQ, Gouaux E (1998) Structure of a glutamate-receptor ligand- binding core in complex with kainate. Nature 395:913–917PubMedCrossRefPubMedCentralGoogle Scholar
  170. 170.
    Mayer ML (2005) Glutamate receptor ion channels. Curr Opin Neurbiol 15:282–288CrossRefGoogle Scholar
  171. 171.
    Endoh T (2004) Characterization of modulatory effects of postsynaptic metabotropic glutamate receptors on calcium currents in rat nucleus tractus solitarius. Brain Res 1024:212–224PubMedCrossRefPubMedCentralGoogle Scholar
  172. 172.
    Sela M, Mozes E, Shearer GM (1972) Thymus-independence of slowly metabolized immunogens. Proc Natl Acad Sci U S A 69:2696–2700PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Bluestein HG, Green I, Maurer PH, Benacerraf B (1972) Specific immune response genes of the guinea pig. V. Influence of the GA and GT immune response genes on the specificity of cellular and humoral immune responses to a terpolymer of L-glutamic acid, L-alanine, and L-tyrosine. J Exp Med 135:98–109PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Levite M (2017) Glutamate, T cells and multiple sclerosis. J Neural Transm (Vienna) 124:775–798CrossRefGoogle Scholar
  175. 175.
    Liu H, Leak RK, Hu X (2016) Neurotransmitter receptors on microglia. Stroke Vasc Neurol 1:52–58PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Boldyrev AA, Bryushkova EA, Vladychenskaya EA (2012) NMDA receptors in immune competent cells. Biochemistry (Mosc) 77:128–134CrossRefGoogle Scholar
  177. 177.
    Ascoli BM, Géa LP, Colombo R, Barbé-Tuana FM, Kapczinski F, Rosa AR (2016) The role of macrophage polarization on bipolar disorder: identifying new therapeutic targets. Aust N Z J Psychiatry 50(7):618–630PubMedCrossRefPubMedCentralGoogle Scholar
  178. 178.
    Lombardi G, Dianzani C, Miglio G, Canonico PL, Fantozzi R (2001) Characterization of ionotropic glutamate receptors in human lymphocytes. Br J Pharmacol 133:936–944PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Chiocchetti A, Miglio G, Mesturini R, Varsaldi F, Mocellin M, Orilieri E, Dianzani C, Fantozzi R, Dianzani U, Lombardi G (2006) Group I mGlu receptor stimulation inhibits activation- induced cell death of human T lymphocytes. Br J Pharmacol 148:760–768PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Lombardi G, Miglio G, Dianzani C, Mesturini R, Varsaldi F, Chiocchetti A, Dianzani U, Fantozzi R (2004) Glutamate modulation of human lymphocyte growth: in vitro studies. Biochem Biophys Res Commun 318:496–502PubMedCrossRefPubMedCentralGoogle Scholar
  181. 181.
    Pacheco R, Oliva H, Martinez-Navío JM, Climent N, Ciruela F, Gatell JM, Gallart T, Mallol J, Lluis C, Franco R (2006) Glutamate released by dendritic cells as a novel modulator of T cell activation. J Immunol 177:6695–6704PubMedCrossRefPubMedCentralGoogle Scholar
  182. 182.
    Kaul M, Lipton SA (2006) Mechanisms of neuronal injury and death in HIV-1 associated dementia. Curr HIV Res 4:307–318PubMedCrossRefPubMedCentralGoogle Scholar
  183. 183.
    Arreola R, Becerril-Villanueva E, Cruz-Fuentes C, Velasco-Velázquez MA, Garcés-Alvarez ME, Hurtado-Alvarado G, Quintero-Fabian S, Pavón L (2015) Immunomodulatory effects mediated by serotonin. J Immunol Res 2015:354957. https://doi.org/10.1155/2015/354957 CrossRefPubMedPubMedCentralGoogle Scholar
  184. 184.
    Hempfling C, Neuhuber WL, Wörl J (2012) Serotonin-immunoreactive neurons and mast cells in the mouse esophagus suggest involvement of serotonin in both motility control and neuroimmune interactions. Neurogastroenterol Motil 24:e67–e78PubMedCrossRefPubMedCentralGoogle Scholar
  185. 185.
    Barcik W, Wawrzyniak M, Akdis CA, O'Mahony L (2017) Immune regulation by histamine and histamine-secreting bacteria. Curr Opin Immunol 48:108–113PubMedCrossRefPubMedCentralGoogle Scholar
  186. 186.
    Holzer P, Farzi A (2014) Neuropeptides and the microbiota-gut-brain axis. Adv Exp Med Biol 817:195–219PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Pintér E, Pozsgai G, Hajna Z, Helyes Z, Szolcsányi J (2014) Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions. Br J Clin Pharmacol 77:5–20PubMedCrossRefPubMedCentralGoogle Scholar
  188. 188.
    Farzi A, Reichmann F, Holzer P (2015) The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour. Acta Physiol (Oxf) 213:603–627CrossRefGoogle Scholar
  189. 189.
    Auteri M, Zizzo MG, Serio R (2015) The GABAergic system and the gastrointestinal physiopathology. Curr Pharm Des 21:4996–5016PubMedCrossRefPubMedCentralGoogle Scholar
  190. 190.
    Gavish M, Weizman A, Karp L, Tyano S, Tanne Z (1986) Decreased peripheral benzodiazepine binding sites in platelets of neuroleptic-treated schizophrenics. Eur J Pharmacol 121:275–279PubMedCrossRefPubMedCentralGoogle Scholar
  191. 191.
    Fonsêca DV, Salgado PR, de Carvalho FL, Salvadori MG, Penha AR, Leite FC, Borges C, Piuvezam MR, Pordeus LC, Sousa DP, Almeida RN (2016) Nerolidol exhibits antinociceptive and anti-inflammatory activity: involvement of the GABAergic system and proinflammatory cytokines. Fundam Clin Pharmacol 30:14–22PubMedCrossRefPubMedCentralGoogle Scholar
  192. 192.
    Dionisio L, José De Rosa M, Bouzat C, Esandi Mdel C (2011) An intrinsic GABAergic system in human lymphocytes. Neuropharmacology 60:513–519PubMedCrossRefPubMedCentralGoogle Scholar
  193. 193.
    Wheeler DW, Thompson AJ, Corletto F, Reckless J, Loke JC, Lapaque N, Grant AJ, Mastroeni P, Grainger DJ, Padgett CL, O'Brien JA, Miller NG, Trowsdale J, Lummis SC, Menon DK, Beech JS (2011) Anaesthetic impairment of immune function is mediated via GABA(A) receptors. PLoS One 6(2):e17152. https://doi.org/10.1371/journal.pone.0017152 CrossRefPubMedPubMedCentralGoogle Scholar
  194. 194.
    Vezzani A, Balosso S, Ravizza T (2008) The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun 22:797–803PubMedCrossRefPubMedCentralGoogle Scholar
  195. 195.
    Crowley T, Cryan JF, Downer EJ, O’Leary OF (2016) Inhibiting neuroinflammation: The role and therapeutic potential of GABA in neuro-immune interactions. Brain Behav Immun 54:260–277PubMedCrossRefPubMedCentralGoogle Scholar
  196. 196.
    Cabot PJ, Carter L, Gaiddon C, Zhang Q, Schäfer M, Loeffler JP, Stein C (1997) Immune cell-derived beta-endorphin. Production, release, and control of inflammatory pain in rats. J Clin Invest 100:142–148PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Ninkovic J, Roy S (2012) The effects of opioids on immune cells, functions and disease. In: Nerve- driven immunity. Mia Levite Ed. Springer, pp 175–202CrossRefGoogle Scholar
  198. 198.
    Holzer P, Hassan AM, Jain P, Reichmann F, Farzi A (2015) Neuroimmune pharmacological approaches. Curr Opin Pharmacol 25:13–22PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Plein LM, Rittner HL (2017) Opioids and the immune system – friend or foe. Br J Pharmacol. https://doi.org/10.1111/bph.13750
  200. 200.
    Rittner HL, Brack A (2007) Leukocytes as mediators of pain and analgesia. Curr Rheumatol Rep 9:503–510PubMedCrossRefPubMedCentralGoogle Scholar
  201. 201.
    Hua S, Dias TH, Pepperall DG, Yang Y (2017) Topical loperamide-encapsulated liposomal gel increases the severity of inflammation and accelerates disease progression in the adjuvant-induced model of experimental rheumatoid arthritis. Front Pharmacol 8:503. https://doi.org/10.3389/fphar.2017.00503 CrossRefPubMedPubMedCentralGoogle Scholar
  202. 202.
    Boland JW, Pockley AG (2017) Influence of opioids on immune function in patients with cancer pain: from bench to bedside. Br J Pharmacol (Jun 8). https://doi.org/10.1111/bph.13903
  203. 203.
    Nakano K, Yamaoka K, Hanami K, Saito K, Sasaguri Y, Yanagihara N, Tanaka S, Katsuki I, Matsushita S, Tanaka Y (2011) Dopamine induces IL-6-dependent IL-17 production via D1-like receptor on CD4 naive T cells and D1-like receptor antagonist SCH-23390 inhibits cartilage destruction in a human rheumatoid arthritis/SCID mouse chimera model. J Immunol 186:3745–3752PubMedCrossRefPubMedCentralGoogle Scholar
  204. 204.
    Killock D (2017) Skin cancer: Propranolol limits melanoma recurrence. Nat Rev Clin Oncol 14(12):714PubMedCrossRefPubMedCentralGoogle Scholar
  205. 205.
    Bose T (2017) Role of immunological memory cells as a therapeutic target in multiple sclerosis. Brain Sci 7(11):pii: E148. https://doi.org/10.3390/brainsci7110148 CrossRefGoogle Scholar
  206. 206.
    Sternberg Z (2012) Sympathetic nervous system dysfunction in multiple sclerosis, linking neurodegeneration to a reduced response to therapy. Curr Pharm Des 18:1635–1644PubMedCrossRefPubMedCentralGoogle Scholar
  207. 207.
    Cosentino M, Marino F (2013) Adrenergic and dopaminergic modulation of immunity in multiple sclerosis: teaching old drugs new tricks? J Neuroimmune Pharmacol 8:163–179PubMedCrossRefPubMedCentralGoogle Scholar
  208. 208.
    Cosentino M, Zaffaroni M, Marino F (2014) Levels of mRNA for dopaminergic receptor D5 in circulating lymphocytes may be associated with subsequent response to interferon-β in patients with multiple sclerosis. J Neuroimmunol 277:193–196PubMedCrossRefPubMedCentralGoogle Scholar
  209. 209.
    Liu Q, Whiteaker P, Morley BJ, Shi FD, Lukas RJ. (2017) Distinctive roles for α7*- and α9*-nicotinic acetylcholine receptors in inflammatory and autoimmune responses in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis. Front Cell Neurosci. 11:287. https://doi.org/10.3389/fncel.2017.00287. eCollection 2017
  210. 210.
    Demakova EV, Korobov VP, Lemkina LM (2003) Determination of gamma-aminobutyric acid concentration and activity of glutamate decarboxylase in blood serum of patients with multiple sclerosis. Klin Lab Diagn 4:15–17Google Scholar
  211. 211.
    Heidari B (2011) Rheumatoid Arthritis: Early diagnosis and treatment outcomes. Caspian J Intern Med 2:161–170PubMedPubMedCentralGoogle Scholar
  212. 212.
    McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219PubMedCrossRefPubMedCentralGoogle Scholar
  213. 213.
    Gierut A, Perlman H, Pope RM (2010) Innate immunity and rheumatoid arthritis. Rheum Dis Clin N Am 36:271–296CrossRefGoogle Scholar
  214. 214.
    Kaplan MJ (2013) Role of neutrophils in systemic autoimmune diseases. Arthritis Res Ther 15:219PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Straub RH, Härle P (2005) Sympathetic neurotransmitters in joint inflammation. Rheum Dis Clin N Am 31:43–59CrossRefGoogle Scholar
  216. 216.
    Fahmy Wahba MG, Shehata Messiha BA, Abo-Saif AA (2015) Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats. Eur J Pharmacol 765:307–315PubMedCrossRefPubMedCentralGoogle Scholar
  217. 217.
    Lowin T, Straub RH (2015) Synovial fibroblasts integrate inflammatory and neuroendocrine stimuli to drive rheumatoid arthritis. Expert Rev Clin Immunol 11:1069–1071PubMedCrossRefPubMedCentralGoogle Scholar
  218. 218.
    Tian J, Dang HN, Yong J, Chui WS, Dizon MP, Yaw CK, Kaufman DL (2011) Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis. Autoimmunity 44:465–470PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Koopman FA, van Maanen MA, Vervoordeldonk MJ, Tak PP (2017) Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis. J Intern Med 282:64–75PubMedCrossRefPubMedCentralGoogle Scholar
  220. 220.
    Lakshmi C, Deb C, Ray C, Ray MR (2005) Reduction of hematotoxicity and augmentation of antitumor efficacy of cyclophosphamide by dopamine. Neoplasma 52:68–73PubMedPubMedCentralGoogle Scholar
  221. 221.
    Chakroborty D, Sarkar C, Yu H, Wang J, Liu Z, Dasgupta PS, Basu S (2011) Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and Kruppel- like factor-2 expression in tumor endothelial cells. Proc Natl Acad Sci U S A 108:20730–20735PubMedPubMedCentralCrossRefGoogle Scholar
  222. 222.
    Basu S, Sarkar C, Chakroborty D, Nagy J, Mitra RB, Dasgupta PS, Mukhopadhyay D. (2004) Ablation of peripheral dopaminergic nerves stimulates malignant tumor growth by inducing vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis. Cancer Res 64:5551–5PubMedCrossRefPubMedCentralGoogle Scholar
  223. 223.
    De Giorgi V, Grazzini M, Benemei S, Marchionni N, Botteri E, Pennacchioli E, Geppetti P, Gandini S (2017) Propranolol for off-label treatment of patients with melanoma: results from a cohort study. JAMA Oncol (Sep 28). https://doi.org/10.1001/jamaoncol.2017.2908. [Epub ahead of print]
  224. 224.
    Coelho M, Soares-Silva C, Brandão D, Marino F, Cosentino M, Ribeiro L (2017) β-adrenergic modulation of cancer cell proliferation: available evidence and clinical perspectives. J Cancer Res Clin Oncol 143:275–291PubMedCrossRefPubMedCentralGoogle Scholar
  225. 225.
    Ribeiro MP, Custódio JB, Santos AE (2017) Ionotropic glutamate receptor antagonists and cancer therapy: time to think out of the box? Cancer Chemother Pharmacol 79:219–225PubMedCrossRefPubMedCentralGoogle Scholar
  226. 226.
    Xu X, Gao Y, Wen L, Zhai Z, Zhang S, Shan F, Feng J (2016) Methionine enkephalin regulates microglia polarization and function. Int Immunopharmacol 40:90–97PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Center of Research in Medical PharmacologyUniversity of InsubriaVareseItaly

Personalised recommendations