Skip to main content

Advertisement

SpringerLink
Log in

Adrenergic modulation of immune cells: an update

  • Invited Review
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Sympathoadrenergic pathways are crucial to the communication between the nervous system and the immune system. The present review addresses emerging issues in the adrenergic modulation of immune cells, including: the specific pattern of adrenoceptor expression on immune cells and their role and changes upon cell differentiation and activation; the production and utilization of noradrenaline and adrenaline by immune cells themselves; the dysregulation of adrenergic immune mechanisms in disease and their potential as novel therapeutic targets. A wide array of sympathoadrenergic therapeutics is currently used for non-immune indications, and could represent an attractive source of non-conventional immunomodulating agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Amenta F, Bronzetti E, Cantalamessa F, El-Assouad D, Felici L, Ricci A, Tayebati SK (2001) Identification of dopamine plasma membrane and vesicular transporters in human peripheral blood lymphocytes. J Neuroimmunol 117:133–142

    CAS  PubMed  Google Scholar 

  • Andreassi JL 2nd, Eggleston WB, Stewart JK (1998) Phenylethanolamine N-methyltransferase mRNA in rat spleen and thymus. Neurosci Lett 241:75–78

    CAS  PubMed  Google Scholar 

  • Arnason BG, Brown M, Maselli R, Karaszewski J, Reder A (1988) Blood lymphocyte beta-adrenergic receptors in multiple sclerosis. Ann NY Acad Sci 540:585–588

    CAS  PubMed  Google Scholar 

  • Arslan F, de Kleijn DP, Pasterkamp G (2011) Innate immune signaling in cardiac ischemia. Nat Rev Cardiol 8:292–300

    CAS  PubMed  Google Scholar 

  • Audus KL, Gordon MA (1982) Characteristics of tricyclic antidepressant binding sites associated with murine lymphocytes from spleen. J Immunopharmacol 4:1–12

    CAS  PubMed  Google Scholar 

  • Baerwald C, Graefe C, von Wichert P, Krause A (1992) Decreased density of beta-adrenergic receptors on peripheral blood mononuclear cells in patients with rheumatoid arthritis. J Rheumatol 19:204–210

    CAS  PubMed  Google Scholar 

  • Baerwald CG, Laufenberg M, Specht T, von Wichert P, Burmester GR, Krause A (1997) Impaired sympathetic influence on the immune response in patients with rheumatoid arthritis due to lymphocyte subset-specific modulation of beta 2-adrenergic receptors. Br J Rheumatol 36:1262–1269

    CAS  PubMed  Google Scholar 

  • Baerwald CG, Wahle M, Ulrichs T, Jonas D, von Bierbrauer A, von Wichert P, Burmester GR, Krause A (1999) Reduced catecholamine response of lymphocytes from patients with rheumatoid arthritis. Immunobiology 200:77–91

    CAS  PubMed  Google Scholar 

  • Baerwald CG, Burmester GR, Krause A (2000) Interactions of autonomic nervous, neuroendocrine, and immune systems in rheumatoid arthritis. Rheum Dis Clin North Am 26:841–857

    CAS  PubMed  Google Scholar 

  • Baker AJ, Fuller RW (1995) Loss of response to beta-adrenoceptor agonists during the maturation of human monocytes to macrophages in vitro. J Leukoc Biol 57:395–400

    CAS  PubMed  Google Scholar 

  • Balsa MD, Gómez N, Unzeta M (1989) Characterization of monoamine oxidase activity present in human granulocytes and lymphocytes. Biochim Biophys Acta 992:140–144

    CAS  PubMed  Google Scholar 

  • Barnes SJ, Ackland GL (2010) Beta-adrenoreceptor modulation of metabolic, endocrine and immunologic function during critical illness. Endocr Metab Immune Disord Drug Targets 10:292–300

    CAS  PubMed  Google Scholar 

  • Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K (2011) Beta blockers and breast cancer mortality: a population-based study. J Clin Oncol 29:2635–2644

    CAS  PubMed  Google Scholar 

  • Bartik MM, Brooks WH, Roszman TL (1993) Modulation of T cell proliferation by stimulation of the beta-adrenergic receptor: lack of correlation between inhibition of T cell proliferation and cAMP accumulation. Cell Immunol 148:408–421

    CAS  PubMed  Google Scholar 

  • Bellinger DL, Lorton D, Felten SY, Felten DL (1992) Innervation of lymphoid organs and implications in development, aging, and autoimmunity. Int J Immunopharmacol 14:329–344

    CAS  PubMed  Google Scholar 

  • Bellinger DL, Millar BA, Perez S, Carter J, Wood C, ThyagaRajan S, Molinaro C, Lubahn C, Lorton D (2008) Sympathetic modulation of immunity: relevance to disease. Cell Immunol 252:27–56

    CAS  PubMed  Google Scholar 

  • Benarroch EE (2009) Autonomic-mediated immunomodulation and potential clinical relevance. Neurology 73:236–242

    PubMed  Google Scholar 

  • Ben-Eliyahu S, Shakhar G, Page GG, Stefanski V, Shakhar K (2000) Suppression of NK cell activity and of resistance to metastasis by stress: a role for adrenal catecholamines and beta-adrenoceptors. Neuroimmunomodulation 8:154–164

    CAS  PubMed  Google Scholar 

  • Benschop RJ, Nijkamp FP, Ballieux RE, Heijnen CJ (1994) The effects of beta-adrenoceptor stimulation on adhesion of human natural killer cells to cultured endothelium. Br J Pharmacol 113:1311–1316

    CAS  PubMed  Google Scholar 

  • Benschop RJ, Schedlowski M, Wienecke H, Jacobs R, Schmidt RE (1997) Adrenergic control of natural killer cell circulation and adhesion. Brain Behav Immun 11:321–332

    CAS  PubMed  Google Scholar 

  • Bergquist J, Silberring J (1998) Identification of catecholamines in the immune system by electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 12:683–688

    CAS  PubMed  Google Scholar 

  • 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 USA 91:12912–12916

    CAS  PubMed  Google Scholar 

  • Berkeley MB, Daussin S, Hernandez MC, Bayer BM (1994) In vitro effects of cocaine, lidocaine and monoamine uptake inhibitors on lymphocyte proliferative responses. Immunopharmacol Immunotoxicol 16:165–178

    CAS  PubMed  Google Scholar 

  • Bidart JM, Assicot M, Bohuon C (1981) Catechol-O-methyl transferase activity in human mononuclear cells. Res. Commun. Chem Pathol Pharmacol 34:47–54

    CAS  Google Scholar 

  • Bidart JM, Motte P, Assicot M, Bohuon C, Bellet D (1983) Catechol-O-methyltransferase activity and aminergic binding sites distribution in human peripheral blood lymphocyte subpopulations. Clin Immunol Immunopathol 26:1–9

    CAS  PubMed  Google Scholar 

  • Blume J, Douglas SD, Evans DL (2011) Immune suppression and immune activation in depression. Brain Behav Immun 25:221–229

    CAS  PubMed  Google Scholar 

  • 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 58:85–90

    CAS  PubMed  Google Scholar 

  • Boreus LO, Hjemdahl P, Lagercrantz H, Martinsson A, Yao AC (1986) Beta-adrenoceptor function in white blood cells from newborn infants: no relation to plasma catecholamine levels. Pediatr Res 20:1152–1155

    CAS  PubMed  Google Scholar 

  • Borger P, Hoekstra Y, Esselink MT, Postma DS, Zaagsma J, Vellenga E, Kauffman HF (1998) Beta-adrenoceptor-mediated inhibition of IFN-gamma, IL-3, and GM-CSF mRNA accumulation in activated human T lymphocytes is solely mediated by the beta2-adrenoceptor subtype. Am J Respir Cell Mol Biol 19:400–407

    CAS  PubMed  Google Scholar 

  • Botta F, Maestroni GJ (2008) Adrenergic modulation of dendritic cell cancer vaccine in a mouse model: role of dendritic cell maturation. J Immunother 31:263–270

    CAS  PubMed  Google Scholar 

  • Brown SL, Charney DS, Woods SW, Heninger GL, Tallman J (1988) Lymphocyte beta-adrenergic receptor binding in panic disorder. Psychopharmacology (Berl) 94:24–28

    CAS  Google Scholar 

  • Bylund DB, Bond RA, Eikenburg DC, Hieble JP, Hills R, Minneman KP, Parra S (2010) Adrenoceptors. Last modified 10 Feb 2011. IUPHAR database (IUPHAR-DB). http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=4. Accessed 24 Aug 2011

  • 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

    CAS  PubMed  Google Scholar 

  • Carlson SL, Trauth K, Brooks WH, Roszman TL (1994) Enhancement of beta-adrenergic-induced cAMP accumulation in activated T-cells. J Cell Physiol 161:39–48

    CAS  PubMed  Google Scholar 

  • Chaitidis P, Billett EE, O’Donnell VB, Fajardo AB, Fitzgerald J, Kuban RJ, Ungethuem U, Kühn H (2004) Th2 response of human peripheral monocytes involves isoform-specific induction of monoamine oxidase-A. J Immunol 173:4821–4827

    CAS  PubMed  Google Scholar 

  • Chaitidis P, O’Donnell V, Kuban RJ, Bermudez-Fajardo A, Ungethuem U, Kühn H (2005) Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and -13. Cytokine 30:366–377

    CAS  PubMed  Google Scholar 

  • Chakroborty D, Sarkar C, Basu B, Dasgupta PS, Basu S (2009) Catecholamines regulate tumor angiogenesis. Cancer Res 69:3727–3730

    CAS  PubMed  Google Scholar 

  • Chello M, Mastroroberto P, Romano R, Cirillo F, Marchese AR (1995) Improved beta-adrenergic receptor function after coronary artery bypass grafting in patients with congestive heart failure. Coron Artery Dis 6:957–963

    CAS  PubMed  Google Scholar 

  • Chou RC, Dong XL, Noble BK, Knight PR, Spengler RN (1998) Adrenergic regulation of macrophage-derived tumor necrosis factor-alpha generation during a chronic polyarthritis pain model. J Neuroimmunol 82:140–148

    CAS  PubMed  Google Scholar 

  • Cole SW, Korin YD, Fahey JL, Zack JA (1998) Norepinephrine accelerates HIV replication via protein kinase A-dependent effects on cytokine production. J Immunol 161:610–616

    CAS  PubMed  Google Scholar 

  • Comi C, Leone M, Bonissoni S, DeFranco S, Bottarel F, Mezzatesta C, Chiocchetti A, Perla F, Monaco F, Dianzani U (2000) Defective T cell Fas function in patients with multiple sclerosis. Neurology 55:921–927

    CAS  PubMed  Google Scholar 

  • Corradi L, Negri F, Parini A, Partesana N, Finardi G (1981) Decreased beta-adrenoceptors in polymorphonucleates in essential hypertension. Boll Soc Ital Biol Sper 57:1766–1770

    CAS  PubMed  Google Scholar 

  • 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 64:975–981

    CAS  PubMed  Google Scholar 

  • Cosentino M, Bombelli R, Ferrari M, Marino F, Rasini E, Maestroni GJM, Conti A, Boveri M, Lecchini S, Frigo G (2000) HPLC-ED measurement of endogenous catecholamines in human immune cells and hematopoietic cell lines. Life Sci 68:283–295

    CAS  PubMed  Google Scholar 

  • Cosentino M, Marino F, Bombelli R, Ferrari M, Rasini E, Lecchini S, Frigo G (2002a) 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 125:125–133

    CAS  PubMed  Google Scholar 

  • Cosentino M, Zaffaroni M, Marino F, Bombelli R, Ferrari M, Rasini E, Lecchini S, Ghezzi A, Frigo GM (2002b) Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis. J Neuroimmunol 133:233–240

    CAS  PubMed  Google Scholar 

  • Cosentino M, Marino F, Bombelli R, Ferrari M, Lecchini S, Frigo G (2003) Unravelling dopamine (and catecholamine) physiopharmacology in lymphocytes: open questions. Trends Immunol 24:581–582

    CAS  PubMed  Google Scholar 

  • Cosentino M, Zaffaroni M, Ferrari M, Marino F, Bombelli R, Rasini E, Frigo G, Ghezzi A, Comi G, Lecchini S (2005) Interferon-γ and interferon-β affect endogenous catecholamines in human peripheral blood mononuclear cells: implications for multiple sclerosis. J Neuroimmunol 162:112–121

    CAS  PubMed  Google Scholar 

  • 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 109:632–642

    CAS  PubMed  Google Scholar 

  • De Giorgi V, Grazzini M, Gandini S, Benemei S, Lotti T, Marchionni N, Geppetti P (2011) Treatment with β-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med 171:779–781

    PubMed  Google Scholar 

  • De Keyser J, Wilczak N, Leta R, Streetland C (1999) Astrocytes in multiple sclerosis lack beta-2 adrenergic receptors. Neurology 53:1628–1633

    PubMed  Google Scholar 

  • De Keyser J, Zeinstra E, Frohman E (2003) Are astrocytes central players in the pathophysiology of multiple sclerosis? Arch Neurol 60:132–136

    PubMed  Google Scholar 

  • De Keyser J, Zeinstra E, Wilczak N (2004) Astrocytic beta2-adrenergic receptors and multiple sclerosis. Neurobiol Dis 15:331–339

    PubMed  Google Scholar 

  • De Keyser J, Steen C, Mostert JP, Koch MW (2008) Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance. J Cereb Blood Flow Metab 28:1645–1651

    PubMed  Google Scholar 

  • De Keyser J, Laureys G, Demol F, Wilczak N, Mostert J, Clinckers R (2010) Astrocytes as potential targets to suppress inflammatory demyelinating lesions in multiple sclerosis. Neurochem Int 57:446–450

    PubMed  Google Scholar 

  • del Rey A, Besedovsky HO (2008) Sympathetic nervous system-immune interactions in autoimmune lymphoproliferative diseases. Neuroimmunomodulation 15:29–36

    CAS  PubMed  Google Scholar 

  • Dzimiri N, Hussain S, Moorji A, Prabhakar G, Bakr S, Kumar M, Almotrefi AA, Halees Z (1995) Characterization of lymphocyte beta-adrenoceptor activity and Gs-protein in patients with rheumatic heart valvular disease. Fundam Clin Pharmacol 9:372–380

    CAS  PubMed  Google Scholar 

  • 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 52:595–638

    CAS  PubMed  Google Scholar 

  • Elliott L, Brooks W, Roszman T (1992) Inhibition of anti-CD3 monoclonal antibody-induced T-cell proliferation by dexamethasone, isoproterenol, or prostaglandin E2 either alone or in combination. Cell Mol Neurobiol 12:411–427

    CAS  PubMed  Google Scholar 

  • Ezeamuzie CI, Shihab PK, Al-Radwan R (2011) Loss of surface beta-2 adrenoceptors accounts for the insensitivity of cultured human monocytes to beta-2 adrenoceptor agonists. Int Immunopharmacol [Epub ahead of print]

  • Feldman RD, Hunninghake GW, McArdle WL (1987) Beta-adrenergic-receptor-mediated suppression of interleukin 2 receptors in human lymphocytes. J Immunol 139:3355–3359

    CAS  PubMed  Google Scholar 

  • Feldman RS, Meyer JS, Quenzer LF (1997) Catecholamines. In: Principles of neuropsychopharmacology. Sinauer Associates Inc., Sunderland, Massachusets, pp 277–344

  • Felten DL (1991) Neurotransmitter signaling of cells of the immune system: important progress, major gaps. Brain Behav Immun 5:2–8

    CAS  PubMed  Google Scholar 

  • Ferrari M, Cosentino M, Marino F, Bombelli R, Rasini E, Lecchini S, Frigo G (2004) Dopaminergic D1-like receptor-dependent inhibition of tyrosine hydroxylase mRNA expression and catecholamine production in human lymphocytes. Biochem Pharmacol 67:865–873

    CAS  PubMed  Google Scholar 

  • Flierl MA, Rittirsch D, Nadeau BA, Chen AJ, Sarma JV, Zetoune FS, McGuire SR, List RP, Day DE, Hoesel LM, Gao H, Van Rooijen N, Huber-Lang MS, Neubig RR, Ward PA (2007) Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature 449:721–725

    CAS  PubMed  Google Scholar 

  • Flierl MA, Rittirsch D, Huber-Lang M, Sarma JV, Ward PA (2008) Catecholamines—Crafty weapons in the inflammatory arsenal of immune/inflammatory cells or opening Pandora’s box? Mol Med 14:195–204

    CAS  PubMed  Google Scholar 

  • Flierl MA, Rittirsch D, Nadeau BA, Sarma JV, Day DE, Lentsch AB, Huber-Lang MS, Ward PA (2009) Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response. PLoS One 4:e4414

    PubMed  Google Scholar 

  • Fragala MS, Kraemer WJ, Mastro AM, Denegar CR, Volek JS, Häkkinen K, Anderson JM, Lee E, Maresh CM (2011) Leukocyte β2-adrenergic receptor expression in response to resistance. Exerc Med Sci Sports Exerc 43:1422–1432

    Google Scholar 

  • Freeman JG, Ryan JJ, Shelburne CP, Bailey DP, Bouton LA, Narasimhachari N, Domen J, Simeon N, Couderc F, Stewart JK (2001) Catecholamines in murine bone marrow derived mast cells. J Neuroimmunol 119:231–238

    CAS  PubMed  Google Scholar 

  • Freier E, Weber CS, Nowottne U, Horn C, Bartels K, Meyer S, Hildebrandt Y, Luetkens T, Cao Y, Pabst C, Muzzulini J, Schnee B, Brunner-Weinzierl MC, Marangolo M, Bokemeyer C, Deter HC, Atanackovic D (2010) Decrease of CD4(+)FOXP3(+) T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor. Psychoneuroendocrinology 35:663–673

    CAS  PubMed  Google Scholar 

  • Friedman EM, Irwin MR (1997) Modulation of immune cell function by the autonomic nervous system. Pharmacol Ther 74:27–38

    CAS  PubMed  Google Scholar 

  • Frohman EM, Monson NL, Lovett-Racke AE, Racke MK (2001) Autonomic regulation of neuroimmunological responses: implications for multiple sclerosis. J Clin Immunol 21:61–73

    CAS  PubMed  Google Scholar 

  • Frohman EM, Racke MK, Raine CS (2006) Multiple sclerosis—the plaque and its pathogenesis. N Engl J Med 354:942–955

    CAS  PubMed  Google Scholar 

  • Garlind A, Johnston JA, Algotsson A, Winblad B, Cowburn RF (1997) Decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in lymphocytes from Alzheimer’s disease patients. Neurosci Lett 226:37–40

    CAS  PubMed  Google Scholar 

  • Ghorpade A, Gendelman HE, Kipnis J (2008) Macrophages, microglia and dendritic cells. In: Ikezu T, Gendelman HE (eds) Neuroimmune pharmacology. Springer, Berlin, pp 89–104

  • Giorelli M, Livrea P, Trojano M (2004) Post-receptorial mechanisms underlie functional disregulation of beta2-adrenergic receptors in lymphocytes from Multiple Sclerosis patients. J Neuroimmunol 155:143–149

    CAS  PubMed  Google Scholar 

  • Giubilei F, Calderaro C, Antonini G, Sepe-Monti M, Tisei P, Brunetti E, Marchione F, Caronti B, Pontieri FE (2004) Increased lymphocyte dopamine beta-hydroxylase immunoreactivity in Alzheimer’s disease: compensatory response to cholinergic deficit? Dement Geriatr Cogn Disord 18:338–341

    CAS  PubMed  Google Scholar 

  • Goldfarb Y, Sorski L, Benish M, Levi B, Melamed R, Ben-Eliyahu S (2011) Improving postoperative immune status and resistance to cancer metastasis: a combined perioperative approach of immunostimulation and prevention of excessive surgical stress responses. Ann Surg 253:798–810

    PubMed  Google Scholar 

  • 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 17:188–196

    CAS  PubMed  Google Scholar 

  • Grisanti LA, Evanson J, Marchus E, Jorissen H, Woster AP, DeKrey W, Sauter ER, Combs CK, Porter JE (2010) Pro-inflammatory responses in human monocytes are beta1-adrenergic receptor subtype dependent. Mol Immunol 47:1244–1254

    CAS  PubMed  Google Scholar 

  • 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 338:648–657

    CAS  PubMed  Google Scholar 

  • 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 Physiol 273:E1203–E1208

    CAS  PubMed  Google Scholar 

  • Gurguis GN, Andrews R, Antai-Otong D, Vo SP, Blakeley JE, Orsulak PJ, Rush AJ (1999a) Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls. Psychopharmacology (Berl) 143:131–140

    CAS  Google Scholar 

  • Gurguis GN, Vo SP, Griffith JM, Rush AJ (1999b) Neutrophil beta(2)-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome. Eur J Pharmacol 386:135–144

    CAS  PubMed  Google Scholar 

  • Hataoka I, Okayama M, Sugi M, Inoue H, Takishima T, Shirato K (1993) Decrease in beta-adrenergic receptors of lymphocytes in spontaneously occurring acute asthma. Chest 104:508–514

    CAS  PubMed  Google Scholar 

  • Heijink IH, Vellenga E, Borger P, Postma DS, Monchy JG, Kauffman HF (2003) Polarized Th1 and Th2 cells are less responsive to negative feedback by receptors coupled to the AC/cAMP system compared to freshly isolated T cells. Br J Pharmacol 138:1441–1450

    CAS  PubMed  Google Scholar 

  • Heijnen CJ, Rouppe van der Voort C, Wulffraat N, van der Net J, Kuis W, Kavelaars A (1996) Functional alpha 1-adrenergic receptors on leukocytes of patients with polyarticular juvenile rheumatoid arthritis. J Neuroimmunol 71:223–226

    CAS  PubMed  Google Scholar 

  • Heijnen CJ, Rouppe van der Voort C, van de Pol M, Kavelaars A (2002) Cytokines regulate alpha(1)-adrenergic receptor mRNA expression in human monocytic cells and endothelial cells. J Neuroimmunol 125:66–72

    CAS  PubMed  Google Scholar 

  • Henry JP, Botton D, Sagne C, Isambert MF, Desnos C, Blanchard V, Raisman-Vozari R, Krejci E, Massoulie J, Gasnier B (1994) Biochemistry and molecular biology of the vesicular monoamine transporter from chromaffin granules. J Exp Biol 196:251–262

    CAS  PubMed  Google Scholar 

  • Hertz L, Chen Y, Gibbs ME, Zang P, Peng L (2004) Astrocytic adrenoceptors: a major drug target in neurological and psychiatric disorders? Curr Drug Targets CNS Neurol Disord 3:239–267

    CAS  PubMed  Google Scholar 

  • Hertz L, Lovatt D, Goldman SA, Nedergaard M (2010) Adrenoceptors in brain: cellular gene expression and effects on astrocytic metabolism and [Ca(2+)]i. Neurochem Int 57:411–420

    CAS  PubMed  Google Scholar 

  • Inbar S, Neeman E, Avraham R, Benish M, Rosenne E, Ben-Eliyahu S (2011) Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity. PLoS One 6:e19246

    CAS  PubMed  Google Scholar 

  • Irwin M (1994) Stress-induced immune suppression: role of brain corticotropin releasing hormone and autonomic nervous system mechanisms. Adv Neuroimmunol 4:29–47

    CAS  PubMed  Google Scholar 

  • Jana M, Dasgupta S, Ghorpade A, Pahan K (2008) Astrocytes, oligodendrocytes, and Schwann cells. In: Ikezu T, Gendelman HE (eds) Neuroimmune pharmacology. Springer, Berlin, pp 69–88

  • Jetschmann JU, Benschop RJ, Jacobs R, Kemper A, Oberbeck R, Schmidt RE, Schedlowski M (1997) Expression and in vivo modulation of alpha- and beta-adrenoceptors on human natural killer (CD16+) cells. J Neuroimmunol 74:159–164

    CAS  PubMed  Google Scholar 

  • Jiang H, Jiang Q, Liu W, Feng J (2006) Parkin suppresses the expression of monoamine oxidases. J Biol Chem 281:8591–8599

    CAS  PubMed  Google Scholar 

  • Jiang JL, Peng YP, Qiu YH, Wang JJ (2007) Effect of endogenous catecholamines on apoptosis of Con A-activated lymphocytes of rats. J Neuroimmunol 192:79–88

    CAS  PubMed  Google Scholar 

  • Jiang JL, Peng YP, Qiu YH, Wang JJ (2009) Adrenoreceptor-coupled signal-transduction mechanisms mediating lymphocyte apoptosis induced by endogenous catecholamines. J Neuroimmunol 213:100–111

    CAS  PubMed  Google Scholar 

  • Josefsson E, Bergquist J, Ekman R, Tarkowski A (1996) Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis. Immunology 88:140–146

    CAS  PubMed  Google Scholar 

  • Kálmán J, Kitajka K, Pákáski M, Zvara A, Juhász A, Vincze G, Janka Z, Puskás LG (2005) Gene expression profile analysis of lymphocytes from Alzheimer’s patients. Psychiatr Genet 15:1–6

    PubMed  Google Scholar 

  • Kamp T, Liebl B, Haen E, Emmerich B, Hallek M (1997) Defects of beta 2-adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression. Eur J Clin Invest 27:121–127

    CAS  PubMed  Google Scholar 

  • Karaszewski JW, Reder AT, Maselli R, Brown M, Arnason BG (1990) Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis. Ann Neurol 27:366–372

    CAS  PubMed  Google Scholar 

  • Karaszewski JW, Reder AT, Anlar B, Kim WC, Arnason BG (1991) Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28− suppressor cell. Ann Neurol 30:42–47

    CAS  PubMed  Google Scholar 

  • Karaszewski JW, Reder AT, Anlar B, Arnason GW (1993) Increased high affinity beta-adrenergic receptor densities and cyclic AMP responses of CD8 cells in multiple sclerosis. J Neuroimmunol 43:1–7

    CAS  PubMed  Google Scholar 

  • Kasprowicz DJ, Kohm AP, Berton MT, Chruscinski AJ, Sharpe A, Sanders VM (2000) Stimulation of the B cell receptor, CD86 (B7-2), and the beta 2-adrenergic receptor intrinsically modulates the level of IgG1 and IgE produced per B cell. J Immunol 165:680–690

    CAS  PubMed  Google Scholar 

  • Kavelaars A, van de Pol M, Zijlstra J, Heijnen CJ (1997) Beta 2-adrenergic activation enhances interleukin-8 production by human monocytes. J Neuroimmunol 77:211–216

    CAS  PubMed  Google Scholar 

  • Khan MM, Sansoni P, Silverman ED, Engleman EG, Melmon KL (1986) Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes. Biochem Pharmacol 35:1137–1142

    CAS  PubMed  Google Scholar 

  • Knudsen JH, Christensen NJ, Bratholm P (1996) Lymphocyte norepinephrine and epinephrine, but not plasma catecholamines predict lymphocyte cAMP production. Life Sci 59:639–647

    CAS  PubMed  Google Scholar 

  • Kohm AP, Sanders VM (1999) Suppression of antigen-specific Th2 cell-dependent IgM and IgG1 production following norepinephrine depletion in vivo. J Immunol 162:5299–5308

    CAS  PubMed  Google Scholar 

  • Kohm AP, Sanders VM (2001) Norepinephrine and beta 2-adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo. Pharmacol Rev 53:487–525

    CAS  PubMed  Google Scholar 

  • Koopman FA, Stoof SP, Straub RH, Van Maanen MA, Vervoordeldonk MJ, Tak PP (2011) Restoring the balance of the autonomic nervous system as an innovative approach to the treatment of rheumatoid arthritis. Mol Med. doi:10.2119/molmed.2011.00065 [Epub ahead of print]

  • Korichneva IL, Tkachuk VA (1990) Alterations in beta-adrenoceptor density on T-lymphocytes upon activation with interleukin-2 and phytohaemagglutinin. Biomed Sci 1:84–88

    CAS  PubMed  Google Scholar 

  • Krause A, Henrich A, Beckh KH, Von Wichert P, Baerwald C (1992) Correlation between density of beta 2-adrenergic receptors on peripheral blood mononuclear cells and serum levels of soluble interleukin-2 receptors in patients with chronic inflammatory diseases. Eur J Clin Invest 22(Suppl 1):47–51

    PubMed  Google Scholar 

  • Kuis W, van Steenwijk C, Sinnema G, Kavelaars A, Prakken B, Helders PJ, Heijnen CJ (1996) The autonomic nervous system and the immune system in juvenile rheumatoid arthritis. Brain Behav Immun 10:387–398

    CAS  PubMed  Google Scholar 

  • Laureys G, Clinckers R, Gerlo S, Spooren A, Wilczak N, Kooijman R, Smolders I, Michotte Y, De Keyser J (2010) Astrocytic beta(2)-adrenergic receptors: from physiology to pathology. Prog Neurobiol 91:189–199

    CAS  PubMed  Google Scholar 

  • Leosco D, Fortunato F, Rengo G, Iaccarino G, Sanzari E, Golino L, Zincarelli C, Canonico V, Marchese M, Koch WJ, Rengo F (2007) Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer’s disease. Neurosci Lett 415:279–282

    CAS  PubMed  Google Scholar 

  • Leposavić G, Pilipović I, Radojević K, Pesić V, Perisić M, Kosec D (2008) Catecholamines as immunomodulators: a role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development. Auton Neurosci 144:1–12

    PubMed  Google Scholar 

  • Levi G, Patrizio M, Bernardo A, Petrucci TC, Agresti C (1993) Human immunodeficiency virus coat protein gp120 inhibits the beta-adrenergic regulation of astroglial and microglial functions. Proc Natl Acad Sci USA 90:1541–1545

    CAS  PubMed  Google Scholar 

  • Levite M (2001) Nervous immunity: neurotransmitters, extracellular K+ and T-cell function. Trends Immunol 22:2–5

    CAS  PubMed  Google Scholar 

  • Li ZJ, Cho CH (2011) Neurotransmitters, more than meets the eye—neurotransmitters and their perspectives in cancer development and therapy. Eur J Pharmacol 667:17–22

    CAS  PubMed  Google Scholar 

  • Li CY, Chou TC, Lee CH, Tsai CS, Loh SH, Wong CS (2003) Adrenaline inhibits lipopolysaccharide-induced macrophage inflammatory protein-1 alpha in human monocytes: the role of beta-adrenergic receptors. Anesth Analg 96:518–523

    CAS  PubMed  Google Scholar 

  • Lombardi MS, Kavelaars A, Schedlowski M, Bijlsma JW, Okihara KL, Van de Pol M, Ochsmann S, Pawlak C, Schmidt RE, Heijnen CJ (1999) Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis. FASEB J 13:715–725

    CAS  PubMed  Google Scholar 

  • Lorton D, Lubahn C, Bellinger DL (2003) Potential use of drugs that target neural-immune pathways in the treatment of rheumatoid arthritis and other autoimmune diseases. Curr Drug Targets Inflamm Allergy 2:1–30

    CAS  PubMed  Google Scholar 

  • Macchi B, Matteucci C, Nocentini U, Caltagirone C, Mastino A (1999) Impaired apoptosis in mitogen-stimulated lymphocytes of patients with multiple sclerosis. NeuroReport 10:399–402

    CAS  PubMed  Google Scholar 

  • Madden KS, Sanders VM, Felten DL (1995) Catecholamine influences and sympathetic neural modulation of immune responsiveness. Annu Rev Pharmacol Toxicol 35:417–448

    CAS  PubMed  Google Scholar 

  • Madden KS, Thyagarajan S, Felten DL (1998) Alterations in sympathetic noradrenergic innervation in lymphoid organs with age. Ann NY Acad Sci 840:262–268

    CAS  PubMed  Google Scholar 

  • Maes M, Lin A, Kenis G, Egyed B, Bosmans E (2000) The effects of noradrenaline and alpha-2 adrenoceptor agents on the production of monocytic products. Psychiatry Res 96:245–253

    CAS  PubMed  Google Scholar 

  • Maestroni GJ (2005) Adrenergic modulation of dendritic cells function: relevance for the immune homeostasis. Curr Neurovasc Res 2:169–173

    PubMed  Google Scholar 

  • Maestroni GJ (2006) Sympathetic nervous system influence on the innate immune response. Ann NY Acad Sci 1069:195–207

    PubMed  Google Scholar 

  • Maisel AS, Harris T, Rearden CA, Michel MC (1990) Beta-adrenergic receptors in lymphocyte subsets after exercise. Alterations in normal individuals and patients with congestive heart failure. Circulation 82:2003–2010

    CAS  PubMed  Google Scholar 

  • Makhlouf K, Weiner HL, Khoury SJ (2002) Potential of beta2-adrenoceptor agonists as add-on therapy for multiple sclerosis: focus on salbutamol (albuterol). CNS Drugs 16:1–8

    CAS  PubMed  Google Scholar 

  • Mamani-Matsuda M, Moynet D, Molimard M, Ferry-Dumazet H, Marit G, Reiffers J, Mossalayi MD (2004) Long-acting beta2-adrenergic formoterol and salmeterol induce the apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol 124:141–150

    CAS  PubMed  Google Scholar 

  • Mandela P, Ordway GA (2006) The norepinephrine transporter and its regulation. J Neurochem 97:310–333

    CAS  PubMed  Google Scholar 

  • Manni M, Maestroni GJ (2008) Sympathetic nervous modulation of the skin innate and adaptive immune response to peptidoglycan but not lipopolysaccharide: involvement of beta-adrenoceptors and relevance in inflammatory diseases. Brain Behav Immun 22:80–88

    CAS  PubMed  Google Scholar 

  • Manni M, Granstein RD, Maestroni G (2011) β2-Adrenergic agonists bias TLR-2 and NOD2 activated dendritic cells towards inducing an IL-17 immune response. Cytokine 55:380–386

    CAS  PubMed  Google Scholar 

  • Mantyh PW, Rogers SD, Allen CJ, Catton MD, Ghilardi JR, Levin LA, Maggio JE, Vigna SR (1995) Beta 2-adrenergic receptors are expressed by glia in vivo in the normal and injured central nervous system in the rat, rabbit, and human. J Neurosci 15:152–164

    CAS  PubMed  Google Scholar 

  • Marazziti D, Consoli G, Masala I, Catena Dell’Osso M, Baroni S (2010) Latest advancements on serotonin and dopamine transporters in lymphocytes. Mini Rev Med Chem 10:32–40

    CAS  PubMed  Google Scholar 

  • 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 27:489–495

    CAS  PubMed  Google Scholar 

  • Markus T, Hansson SR, Cronberg T, Cilio C, Wieloch T, Ley D (2010) β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices. J Neuroinflammation 7:94

    CAS  PubMed  Google Scholar 

  • Marshall GD (2004) Neuroendocrine mechanisms of immune dysregulation: applications to allergy and asthma. Ann Allergy Asthma Immunol 93(2 Suppl 1):S11–S17

    Google Scholar 

  • Marshall GD Jr, Agarwal SK (2000) Stress, immune regulation, and immunity: applications for asthma. Allergy Asthma Proc 21:241–246

    PubMed  Google Scholar 

  • McNamee EN, Ryan KM, Kilroy D, Connor TJ (2010) Noradrenaline induces IL-1ra and IL-1 type II receptor expression in primary glial cells and protects against IL-1beta-induced neurotoxicity. Eur J Pharmacol 626:219–228

    CAS  PubMed  Google Scholar 

  • Melmon KL, Bourne HR, Weinstein Y, Shearer GM, Kram J, Bauminger S (1974) Hemolytic plaque formation by leukocytes in vitro. Control by vasoactive hormones. J Clin Invest 53:13–21

    CAS  PubMed  Google Scholar 

  • Mignini F, Tomassoni D, Traini E, Amenta F (2009) Dopamine, vesicular transporters and dopamine receptor expression and localization in rat thymus and spleen. J Neuroimmunol 206:5–13

    CAS  PubMed  Google Scholar 

  • Miller LE, Jüsten HP, Schölmerich J, Straub RH (2000) 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 14:2097–2107

    CAS  PubMed  Google Scholar 

  • Miller LE, Grifka J, Schölmerich J, Straub RH (2002) Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritis. J Rheumatol 29:427–435

    CAS  PubMed  Google Scholar 

  • Mizuno K, Takahashi HK, Iwagaki H, Katsuno G, Kamurul HA, Ohtani S, Mori S, Yoshino T, Nishibori M, Tanaka N (2005) Beta2-adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12 production in monocytes. Immunol Lett 101:168–172

    CAS  PubMed  Google Scholar 

  • Musgrave IF, Seifert R (1994) Human neutrophils and HL-60 cells do not possess alpha 2-adrenoceptors. Biochem Pharmacol 47:233–239

    CAS  PubMed  Google Scholar 

  • Musso NR, Brenci S, Setti M, Indiveri F, Lotti G (1996) Catecholamine content and in vitro catecholamine synthesis in peripheral human lymphocytes. J Clin Endocrinol Metab 81:3553–3557

    CAS  PubMed  Google Scholar 

  • Nance DM, Sanders VM (2007) Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 21:736–745

    CAS  PubMed  Google Scholar 

  • Nielson CP (1987) Beta-adrenergic modulation of the polymorphonuclear leukocyte respiratory burst is dependent upon the mechanism of cell activation. J Immunol 139:2392–2397

    CAS  PubMed  Google Scholar 

  • Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343:938–952

    CAS  PubMed  Google Scholar 

  • Page GG, Ben-Eliyahu S (2000) Natural killer cell activity and resistance to tumor metastasis in prepubescent rats: deficient baselines, but invulnerability to stress and beta-adrenergic stimulation. Neuroimmunomodulation 7:160–168

    CAS  PubMed  Google Scholar 

  • Page GG, Fennelly AM, Littleton-Kearney MT, Ben-Eliyahu S (2008) Male-female differences in the impact of beta-adrenoceptor stimulation on resistance to experimental metastasis: exploring the effects of age and gonadal hormone involvement. J Neuroimmunol 193:113–119

    CAS  PubMed  Google Scholar 

  • Paietta E, Schwarzmeier JD (1983) Differences in beta-adrenergic receptor density and adenylate cyclase activity between normal and leukaemic leukocytes. Eur J Clin Invest 13:339–346

    CAS  PubMed  Google Scholar 

  • 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 100:1513–1519

    CAS  PubMed  Google Scholar 

  • Pender MP (1998) Genetically determined failure of activation-induced apoptosis of autoreactive T cells as a cause of multiple sclerosis. Lancet 351:978–981

    CAS  PubMed  Google Scholar 

  • Pintar JE, Breakefield XO (1982) Monoamine oxidase (MAO) activity as a determinant in human neurophysiology. Behav Genet 12:53–68

    CAS  PubMed  Google Scholar 

  • Pohl A, Otto J, Urbanek R (1991) Beta-2-adrenoceptors of polymorphonuclear leukocytes in children with atopic dermatitis. Their number and affinity to the radioligand [125I]-cyanopindolol. Int Arch Allergy Appl Immunol 95:261–265

    CAS  PubMed  Google Scholar 

  • Powe DG, Voss MJ, Zänker KS, Habashy HO, Green AR, Ellis IO, Entschladen F (2010) Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget 1:628–638

    PubMed  Google Scholar 

  • 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 272:357–365

    PubMed  Google Scholar 

  • Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia A-S, McNamara JO, Williams SM (eds) (2001) Criteria that define a neurotransmitter. In: Neuroscience, 2nd ed. Sinauer Associates, Sunderland. http://www.ncbi.nlm.nih.gov/books/NBK10957/?rendertype=box&id=A377. Accessed 24 Aug 2011

  • Qiu YH, Peng YP, Jiang JM, Wang JJ (2004) Expression of tyrosine hydroxylase in lymphocytes and effect of endogenous catecholamines on lymphocyte function. Neuroimmunomodulation 11:75–83

    CAS  PubMed  Google Scholar 

  • Qiu YH, Cheng C, Dai L, Peng YP (2005) Effect of endogenous catecholamines in lymphocytes on lymphocyte function. J Neuroimmunol 167:45–52

    CAS  PubMed  Google Scholar 

  • Radojcic T, Baird S, Darko D, Smith D, Bulloch K (1991) Changes in beta-adrenergic receptor distribution on immunocytes during differentiation: an analysis of T cells and macrophages. J Neurosci Res 30:328–335

    CAS  PubMed  Google Scholar 

  • Rainer TH, Lam N, Cocks RA (1999) Adrenaline upregulates monocyte L-selectin in vitro. Resuscitation 43:47–55

    CAS  PubMed  Google Scholar 

  • Rajda C, Bencsik K, Vecsei LL, Bergquist J (2002) Catecholamine levels in peripheral blood lymphocytes from multiple sclerosis patients. J Neuroimmunol 124:93–100

    CAS  PubMed  Google Scholar 

  • Ratge D, Wiedemann A, Kohse KP, Wisser H (1988) Alterations of beta-adrenoceptors on human leukocyte subsets induced by dynamic exercise: effect of prednisone. Clin Exp Pharmacol Physiol 15:43–53

    CAS  PubMed  Google Scholar 

  • Reguzzoni M, Cosentino M, Rasini E, Marino F, Ferrari M, Bombelli R, Congiu T, Protasoni M, Quacci D, Lecchini S, Raspanti M, Frigo G (2002) Ultrastructural localization of tyrosine hydroxylase in human peripheral blood mononuclear cells: effect of stimulation with phytohaemagglutinin. Cell Tissue Res 310:297–304

    CAS  PubMed  Google Scholar 

  • 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. Arthr Res Ther 12:R110

    Google Scholar 

  • Rouppe van der Voort C, Kavelaars A, van de Pol M, Heijnen CJ (1999) Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes. J Neuroimmunol 95:165–173

    CAS  PubMed  Google Scholar 

  • Rouppe van der Voort C, Heijnen CJ, Wulffraat N, Kuis W, Kavelaars A (2000a) Stress induces increases in IL-6 production by leucocytes of patients with the chronic inflammatory disease juvenile rheumatoid arthritis: a putative role for alpha(1)-adrenergic receptors. J Neuroimmunol 110:223–229

    Google Scholar 

  • Rouppe van der Voort C, Kavelaars A, van de Pol M, Heijnen CJ (2000b) Noradrenaline induces the phosphorylation of ERK-2 in human peripheral blood mononuclear cells after induction of α1-adrenergic receptors. J Neuroimmunol 108:82–91

    CAS  PubMed  Google Scholar 

  • Sanders VM, Baker RA, Ramer-Quinn DS, Kasprowicz DJ, Fuchs BA, Street NE (1997) Differential expression of the beta-2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help. J Immunol 158:4200–4210

    CAS  PubMed  Google Scholar 

  • 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 156:93–99

    CAS  PubMed  Google Scholar 

  • Schopf RE, Lemmel EM (1983) Control of the production of oxygen intermediates of human polymorphonuclear leukocytes and monocytes by beta-adrenergic receptors. J Immunopharmacol 5:203–216

    CAS  PubMed  Google Scholar 

  • Schwab KO, Bartels H, Martin C, Leichtenschlag EM (1993) Decreased beta 2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: an additional cause of severe hypoglycaemia in childhood diabetes? Eur J Pediatr 152:797–801

    CAS  PubMed  Google Scholar 

  • Shah SM, Carey IM, Owen CG, Harris T, Dewilde S, Cook DG (2011) Does β-adrenoceptor blocker therapy improve cancer survival? Findings from a population-based retrospective cohort study. Br J Clin Pharmacol 72:157–161

    CAS  PubMed  Google Scholar 

  • Shakhar G, Ben-Eliyahu S (1998) In vivo beta-adrenergic stimulation suppresses natural killer activity and compromises resistance to tumor metastasis in rats. J Immunol 160:3251–3258

    CAS  PubMed  Google Scholar 

  • Sharief MK, Douglas M, Noori M, Semra YK (2002) The expression of pro- and anti-apoptosis Bcl-2 family proteins in lymphocytes from patients with multiple sclerosis. J Neuroimmunol 125:155–162

    CAS  PubMed  Google Scholar 

  • Sheppard JR, Gormus R, Moldow CF (1977) Catecholamine hormone receptors are reduced on chronic lymphocytic leukaemic lymphocytes. Nature 269:693–695

    CAS  PubMed  Google Scholar 

  • Sloan EK, Capitanio JP, Cole SW (2008) Stress-induced remodeling of lymphoid innervation. Brain Behav Immun 22:15–21

    CAS  PubMed  Google Scholar 

  • Sneader W (2005) Drug discovery: a history. John, Chichester, pp 155–157

    Google Scholar 

  • 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 18:603–605

    CAS  PubMed  Google Scholar 

  • Spengler RN, Chensue SW, Giacherio DA, Blenk N, Kunkel SL (1994) Endogenous norepinephrine regulates tumor necrosis factor-alpha production from macrophages in vitro. J Immunol 152:3024–3031

    CAS  PubMed  Google Scholar 

  • Spooren A, Mestdagh P, Rondou P, Kolmus K, Haegeman G, Gerlo S (2011) IL-1β potently stabilizes IL-6 mRNA in human astrocytes. Biochem Pharmacol 81:1004–1015

    CAS  PubMed  Google Scholar 

  • Stefanski V, Ben-Eliyahu S (1996) Social confrontation and tumor metastasis in rats: defeat and beta-adrenergic mechanisms. Physiol Behav 60:277–282

    CAS  PubMed  Google Scholar 

  • Straub RH (2004) Complexity of the bi-directional neuroimmune junction in the spleen. Trends Pharmacol Sci 25:640–646

    CAS  PubMed  Google Scholar 

  • Straub RH, Härle P (2005) Sympathetic neurotransmitters in joint inflammation. Rheum Dis Clin North Am 31:43–59, viii

    Google Scholar 

  • Straub RH, Günzler C, Miller LE, Cutolo M, Schölmerich J, Schill S (2002a) Anti-inflammatory cooperativity of corticosteroids and norepinephrine in rheumatoid arthritis synovial tissue in vivo and in vitro. FASEB J 16:993–1000

    CAS  PubMed  Google Scholar 

  • Straub RH, Kittner JM, Heijnen C, Schedlowski M, Schmidt RE, Jacobs R (2002b) Infusion of epinephrine decreases serum levels of cortisol and 17-hydroxyprogesterone in patients with rheumatoid arthritis. J Rheumatol 29:1659–1664

    CAS  PubMed  Google Scholar 

  • Straub RH, Dhabhar FS, Bijlsma JW, Cutolo M (2005) How psychological stress via hormones and nerve fibers may exacerbate rheumatoid arthritis. Arthritis Rheum 52:16–26

    PubMed  Google Scholar 

  • Straub RH, Wiest R, Strauch UG, Härle P, Schölmerich J (2006) The role of the sympathetic nervous system in intestinal inflammation. Gut 55:1640–1649

    CAS  PubMed  Google Scholar 

  • Swanson MA, Lee WT, Sanders VM (2001) IFN-gamma production by Th1 cells generated from naive CD4+ T cells exposed to norepinephrine. J Immunol 166:232–240

    CAS  PubMed  Google Scholar 

  • Szelenyi J, Selmeczy Z, Brozik A, Medgyesi D, Magocsi M (2006) Dual beta-adrenergic modulation in the immune system: stimulus-dependent effect of isoproterenol on MAPK activation and inflammatory mediator production in macrophages. Neurochem Int 49:94–103

    CAS  PubMed  Google Scholar 

  • 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 304:634–642

    CAS  PubMed  Google Scholar 

  • Takahashi HK, Iwagaki H, Mori S, Yoshino T, Tanaka N, Nishibori M (2004) Beta 2-adrenergic receptor agonist induces IL-18 production without IL-12 production. J Neuroimmunol 151:137–147

    CAS  PubMed  Google Scholar 

  • 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 58:127–131

    CAS  PubMed  Google Scholar 

  • Thorpe LW, Westlund KN, Kochersperger LM, Abell CW, Denney RM (1987) Immunocytochemical localization of monoamine oxidases A and B in human peripheral tissues and brain. J Histochem Cytochem 35:23–32

    CAS  PubMed  Google Scholar 

  • Tomozawa Y, Yabuuchi K, Inoue T, Satoh M (1995) Participation of cAMP and cAMP-dependent protein kinase in beta-adrenoceptor-mediated interleukin-1 beta mRNA induction in cultured microglia. Neurosci Res 22:399–409

    CAS  PubMed  Google Scholar 

  • Townend JN, Virk SJ, Qiang FX, Lawson N, Bain RJ, Davies MK (1993) Lymphocyte beta adrenoceptor upregulation and improved cardiac response to adrenergic stimulation following converting enzyme inhibition in congestive heart failure. Eur Heart J 14:243–250

    CAS  PubMed  Google Scholar 

  • Tsavaris N, Konstantopoulos K, Vaidakis S, Koumakis K, Pangalis G (1995) Cytochemical determination of monoamine oxidase activity in lymphocytes and neutrophils of schizophrenic patients. Haematologia (Budap) 26:143–146

    CAS  Google Scholar 

  • Vago T, Norbiato G, Baldi G, Chebat E, Bertora P, Bevilacqua M (1990) Respiratory-burst stimulants desensitize beta-2 adrenoceptors on human polymorphonuclear leukocytes. Int J Tissue React 12:53–58

    CAS  PubMed  Google Scholar 

  • Wahle M, Krause A, Ulrichs T, Jonas D, von Wichert P, Burmester GR, Baerwald CG (1999) Disease activity related catecholamine response of lymphocytes from patients with rheumatoid arthritis. Ann NY Acad Sci 876:287–296

    CAS  PubMed  Google Scholar 

  • Wahle M, Kölker S, Krause A, Burmester GR, Baerwald CG (2001a) Impaired catecholaminergic signalling of B lymphocytes in patients with chronic rheumatic diseases. Ann Rheum Dis 60:505–510

    CAS  PubMed  Google Scholar 

  • Wahle M, Stachetzki U, Krause A, Pierer M, Häntzschel H, Baerwald CG (2001b) Regulation of beta2-adrenergic receptors on CD4 and CD8 positive lymphocytes by cytokines in vitro. Cytokine 16:205–209

    CAS  PubMed  Google Scholar 

  • Wahle M, Krause A, Pierer M, Hantzschel H, Baerwald CG (2002) Immunopathogenesis of rheumatic diseases in the context of neuroendocrine interactions. Ann NY Acad Sci 966:355–364

    CAS  PubMed  Google Scholar 

  • Wahle M, Hanefeld G, Brunn S, Straub RH, Wagner U, Krause A, Häntzschel H, Baerwald CG (2006) Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile in patients with rheumatoid arthritis. Arthr Res Ther 8:R138

    Google Scholar 

  • Wang J, Li J, Sheng X, Zhao H, Cao XD, Wang YQ, Wu GC (2010) Beta-adrenoceptor mediated surgery-induced production of pro-inflammatory cytokines in rat microglia cells. J Neuroimmunol 223:77–83

    CAS  PubMed  Google Scholar 

  • Werner C, Werdan K, Pönicke K, Brodde OE (2001) Impaired beta-adrenergic control of immune function in patients with chronic heart failure: reversal by beta1-blocker treatment. Basic Res Cardiol 96:290–298

    CAS  PubMed  Google Scholar 

  • Werstiuk ES, Steiner M, Burns T (1990) Studies on leukocyte beta-adrenergic receptors in depression: a critical appraisal. Life Sci 47:85–105

    CAS  PubMed  Google Scholar 

  • Whalen MM, Bankhurst AD (1990) Effects of beta-adrenergic receptor activation, cholera toxin and forskolin on human natural killer cell function. Biochem J 272:327–331

    CAS  PubMed  Google Scholar 

  • Wrona D (2006) Neural-immune interactions: an integrative view of the bidirectional relationship between the brain and immune systems. J Neuroimmunol 172:38–58

    CAS  PubMed  Google Scholar 

  • Wu JR, Chang HR, Huang TY, Chiang CH, Chen SS (1996) Reduction in lymphocyte beta-adrenergic receptor density in infants and children with heart failure secondary to congenital heart disease. Am J Cardiol 77:170–174

    CAS  PubMed  Google Scholar 

  • Xu BY, Pirskanen R, Lefvert AK (1998) Antibodies against beta1 and beta2 adrenergic receptors in myasthenia gravis. J Neuroimmunol 91:82–88

    CAS  PubMed  Google Scholar 

  • Xu B, Zhang WS, Yang JL, Lû N, Deng XM, Xu H, Zhang YQ (2010) Evidence for suppression of spinal glial activation by dexmedetomidine in a rat model of monoarthritis. Clin Exp Pharmacol Physiol 37:e158–e166

    CAS  PubMed  Google Scholar 

  • Yanagawa Y, Matsumoto M, Togashi H (2010) Enhanced dendritic cell antigen uptake via alpha2 adrenoceptor-mediated PI3K activation following brief exposure to noradrenaline. J Immunol 185:5762–5768

    CAS  PubMed  Google Scholar 

  • Yu BH, Dimsdale JE, Mills PJ (1999) Psychological states and lymphocyte beta-adrenergic receptor responsiveness. Neuropsychopharmacology 21:147–152

    CAS  PubMed  Google Scholar 

  • 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 214:315–321

    CAS  PubMed  Google Scholar 

  • Zeinstra E, Wilczak N, De Keyser J (2000) [3H]dihydroalprenolol binding to beta adrenergic receptors in multiple sclerosis brain. Neurosci Lett 289:75–77

    CAS  PubMed  Google Scholar 

  • Ziegler MG, Bao X, Kennedy BP, Joyner A, Enns R (2002) Location, development, control, and function of extraadrenal phenylethanolamine N-methyltransferase. Ann NY Acad Sci 971:76–82

    CAS  PubMed  Google Scholar 

  • Zoukos Y, Leonard JP, Thomaides T, Thompson AJ, Cuzner ML (1992) Beta-Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: a regulatory role for cortisol and interleukin-1. Ann Neurol 31:657–662

    CAS  PubMed  Google Scholar 

  • Zoukos Y, Kidd D, Woodroofe MN, Kendall BE, Thompson AJ, Cuzner ML (1994) Increased expression of high affinity IL-2 receptors and β-adrenoceptors on peripheral blood mononuclear cells is associated with clinical and MRI activity in multiple sclerosis. Brain 117:307–315

    PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9, 21100, Varese, VA, Italy

    Franca Marino & Marco Cosentino

Authors
  1. Franca Marino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Cosentino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco Cosentino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marino, F., Cosentino, M. Adrenergic modulation of immune cells: an update. Amino Acids 45, 55–71 (2013). https://doi.org/10.1007/s00726-011-1186-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-011-1186-6

Keywords

Search

Navigation