Skip to main content
SpringerLink
Log in

NPY and Immune Functions: Implications for Health and Disease

  • Chapter
Neuropeptide Y and Related Peptides

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 162))

Abstract

It is now well established that the nervous system and the immune system are connected in a reciprocal manner. A major pathway in the neuroimmune crosstalk is provided by the sympathetic nervous system (SNS). Though this interaction is thought to be predominantly mediated by catecholamines (CA), compelling evidence is now available indicating that neuropeptide Y (NPY), released from sympathetic nerves within immune organs, also exerts profound influence on both cellular and humoral immune functions. NPY interferes with critical immune functions, such as differentiation of T helper cells, monocyte mediator release, natural killer (NK) cell activation, and immune cell redistribution. Additionally, NPY also modulates the outcome of CA induced immune alterations in vitro and in vivo, thereby acting as a neuroimmune cotransmitter. In this chapter, we summarize key findings from the interaction between NPY and immune functions and discuss implications for the clinical situation. In addition, fields of future research on this interesting topic are outlined.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793

    PubMed  CAS  Google Scholar 

  • Ahmed AA, Wahbi A, Nordlind K, Kharazmi A, Sundqvist KG, Mutt V, Liden S (1998) In vitro Leishmania major promastigote-induced macrophage migration is modulated by sensory and autonomic neuropeptides. Scand J Immunol 48:79–85

    PubMed  CAS  Google Scholar 

  • Ahmed AA, Wahbi AH, Nordlin K (2001) Neuropeptides modulate a murine monocyte/ macrophage cell line capacity for phagocytosis and killing of Leishmania major parasites. Immunopharmacol Immunotoxicol 23:397–409

    PubMed  CAS  Google Scholar 

  • Ahmed M, Bjurholm A, Theodorsson E, Schultzberg M, Kreicbergs A (1995) Neuropeptide Y-and vasoactive intestinal polypeptide-like immunoreactivity in adjuvant arthritis: effects of capsaicin treatment. Neuropeptides 29:33–43

    PubMed  CAS  Google Scholar 

  • Andrade-Mena CE (1997) Inhibition of gamma interferon synthesis by catecholamines. J Neuroimmunol 76:10–14

    PubMed  CAS  Google Scholar 

  • Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E (1993) Relation between the intra-articular temperature of the temporomandibular joint and the presence of neuropeptide Y-like immunoreactivity in the joint fluid. A clinical study. Acta Odontol Scand 51:1–8

    PubMed  CAS  Google Scholar 

  • Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E (1995) Neuropeptides in the arthritic TMJ and symptoms and signs from the stomatognathic system with special consideration to rheumatoid arthritis. J Orofac Pain 9:215–225

    PubMed  CAS  Google Scholar 

  • Arinbjarnarson S, Jonsson T, Steinsson K, Sigfusson A, Jonsson H, Geirsson A, Thorsteinsson J, Valdimarsson H (1997) IgA rheumatoid factor correlates with changes in B and T lymphocyte subsets and disease manifestations in rheumatoid arthritis. J Rheumatol 24:269–274

    PubMed  CAS  Google Scholar 

  • Arzt E, Pereda MP, Castro CP, Pagotto U, Renner U, Stalla GK (1999) Pathophysiological role of the cytokine network in the anterior pituitary gland. Front Neuroendocrinol 20:71–95

    PubMed  CAS  Google Scholar 

  • Arzubiaga C, Morrow J, Roberts LJ, Biaggioni I (1991) Neuropeptide Y, a putative cotransmitter in noradrenergic neurons, induces mast cell degranulation but not prostaglandin D2 release. J Allergy Clin Immunol 87:88–93

    PubMed  CAS  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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Barbany G, Friedman WJ, Persson H (1991) Lymphocyte-mediated regulation of neurotransmitter gene expression in rat sympathetic ganglia. J Neuroimmunol 32:97–104

    PubMed  CAS  Google Scholar 

  • Barnea A, Roberts J, Keller P, Word RA (2001) Interleukin-1 beta induces expression of neuropeptide Y in primary astrocyte cultures in a cytokine-specific manner: induction in human but not rat astrocytes. Brain Res 896:137–145

    PubMed  CAS  Google Scholar 

  • Bedoui S, Kuhlmann S, Nave H, Drube J, Pabst R, von Hörsten S (2001) Differential effects of neuropeptide Y (NPY) on leukocyte subsets in the blood: mobilization of B-1-like B-lymphocytes and activated monocytes. J Neuroimmunol 117:125–132

    PubMed  CAS  Google Scholar 

  • Bedoui S, Lechner S, Gebhardt T, Nave H, Beck-Sickinger AG, Straub RH, Pabst R, von Horsten S (2002) NPY modulates epinephrine-induced leukocytosis via Y-1 and Y-5 receptor activation in vivo: sympathetic co-transmission during leukocyte mobilization. J Neuroimmunol 132:25–33

    PubMed  CAS  Google Scholar 

  • Bedoui S, Kawamura N, Straub RH, Pabst R, Yamamura T, von Hörsten S (2003a) Contributions of NPY to the neuroimmune crosstalk. J Neuroimmunol 134:1–11

    PubMed  CAS  Google Scholar 

  • Bedoui S, Miyake S, Lin Y, Miyamoto K, Oki S, Kawamura N, Beck-Sickinger A, Hörsten Sv, Yamamura T (2003) Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis: Neuropeptide Y1 receptor-specific inhibition of autoreactive Th1 responses in vivo. J Immunol 171:3451–3458

    PubMed  CAS  Google Scholar 

  • Benschop RJ, Rodriguez-Feuerhahn M, Schedlowski M (1996) Catecholamine-induced leukocytosis: early observations, current research, and future directions. Brain Behav Immun 10:77–91

    PubMed  CAS  Google Scholar 

  • Bracci-Laudiero L, Aloe L, Stenfors C, Theodorsson E, Lundeberg T (1998) Development of systemic lupus erythematosus in mice is associated with alteration of neuropeptide concentrations in inflamed kidneys and immunoregulatory organs. Neurosci Lett 248:97–100

    PubMed  CAS  Google Scholar 

  • Burmester GR, Stuhlmuller B, Keyszer G, Kinne RW (1997) Mononuclear phagocytes and rheumatoid synovitis. Mastermind or workhorse in arthritis? Arthritis Rheum 40:5–18

    PubMed  CAS  Google Scholar 

  • Cavallotti C, Artico M, Cavallotti D (1999) Occurrence of adrenergic nerve fibers and of noradrenaline in thymus gland of juvenile and aged rats. Immunol Lett 70:53–62

    PubMed  CAS  Google Scholar 

  • Chelmicka-Schorr E, Checinski M, Arnason BG (1988) Chemical sympathectomy augments the severity of experimental allergic encephalomyelitis. J Neuroimmunol 17:347–350

    PubMed  CAS  Google Scholar 

  • Chelmicka-Schorr E, Kwasniewski MN, Thomas BE, Arnason BG (1989) The beta-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats. J Neuroimmunol 25:203–207

    PubMed  CAS  Google Scholar 

  • Correale J, Mix E, Olsson T, Kostulas V, Fredrikson S, Hojeberg B, Link H (1991) CD5+ B cells and CD4-8-T cells in neuroimmunological diseases. J Neuroimmunol 32:123–132

    PubMed  CAS  Google Scholar 

  • Correale J, Mix E, Olsson T, Kostulas V, Fredrikson S, Hojeberg B, Link H (1991) CD5+ B cells and CD4-8-T cells in neuroimmunological diseases. J Neuroimmunol 32:123–132

    PubMed  CAS  Google Scholar 

  • Correale J de Los Milagros Bassani Molinas (2002) Oligoclonal bands and antibody responses in Multiple Sclerosis. J Neurol 249:375–389

    PubMed  CAS  Google Scholar 

  • Cross LJ, Beck-Sickinger AG, Bienert M, Gaida W, Jung G, Krause E, Ennis M (1996) Structure activity studies of mast cell activation and hypotension induced by neuropeptide Y (NPY), centrally truncated and C-terminal NPY analogues. Br J Pharmacol 117:325–332

    PubMed  CAS  Google Scholar 

  • Cunnick JE, Lysle DT, Armfield A, Rabin BS (1988) Shock-induced modulation of lymphocyte responsiveness and natural killer activity: differential mechanisms of induction. Brain Behav Immun 2:102–113

    PubMed  CAS  Google Scholar 

  • D’Hooge R, De Deyn PP, Verzwijvelen A, De Block J, De Potter WP (1990) Storage and fast transport of noradrenaline, dopamine beta-hydroxylase and neuropeptide Y in dog sciatic nerve axons. Life Sci 47:1851–1859

    PubMed  Google Scholar 

  • Davidson A, Diamond B (2001) Autoimmune diseases. N Engl J Med 345:340–350

    PubMed  CAS  Google Scholar 

  • de Boer NK, Ammerlaan WA, Meedendorp B, Kroese FG (1992) CD5 B cells in the rat? Ann NY Acad Sci 651:157–159

    PubMed  Google Scholar 

  • de la Fuente M, Bernaez I, Del Rio M, Hernanz A (1993) Stimulation of murine peritoneal macrophage functions by neuropeptide Y and peptide YY Involvement of protein kinase C. Immunology 80:259–265

    PubMed  Google Scholar 

  • de la Fuente M, Del Rio M, Medina S (2001) Changes with aging in the modulation by neuropeptide Y of murine peritoneal macrophage functions. J Neuroimmunol 116:156–167

    PubMed  Google Scholar 

  • de Seze J, Arndt C, Stojkovic T, Ayachi M, Gauvrit JY, Bughin M, Saint MT, Pruvo JP, Hache JC, Vermersch P (2001) Pupillary disturbances in multiple sclerosis: correlation with MRI findings. J Neurol Sci 188:37–41

    PubMed  Google Scholar 

  • Downing JE Miyan JA (2000) Neural immunoregulation: emerging roles for nerves in immune homeostasis and disease. Immunol Today 21:281–289

    PubMed  CAS  Google Scholar 

  • Dureus P, Louis D, Grant AV, Bilfinger TV, Stefano GB (1993) Neuropeptide Y inhibits human and invertebrate immunocyte chemotaxis, chemokinesis, and spontaneous activation. Cell Mol Neurobiol 13:541–546

    PubMed  CAS  Google Scholar 

  • Ekblad E, Edvinsson L, Wahlestedt C, Uddman R, Hakanson R, Sundler F (1984) Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers. Regul Pept 8:225–235

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Elitsur Y, Luk GD, Colberg M, Gesell MS, Dosescu J, Moshier JA (1994) Neuropeptide Y (NPY) enhances proliferation of human colonic lamina propria lymphocytes. Neuropeptides 26:289–295

    PubMed  CAS  Google Scholar 

  • Ericsson A, Schalling M, Mclntyre KR, Lundberg JM, Larhammar D, Seroogy K, Hökfelt T, Persson H (1987) Detection of neuropeptide Y and its mRNA in megakaryocytes: enhanced levels in certain autoimmune mice. Proc Natl Acad Sci USA 84:5585–5589

    PubMed  CAS  Google Scholar 

  • Ericsson A, Hemsen A, Lundberg JM, Persson H (1991) Detection of neuropeptide Y-like immunoreactivity and messenger RNA in rat platelets: the effects of vinblastine, reserpine, and dexamethasone on NPY expression in blood cells. Exp Cell Res 192:604–611

    PubMed  CAS  Google Scholar 

  • Eruklar SD (1994). Molecular, cellular and medical aspects. In: Siegel G, Albers J, Agranoff BW, Albers R, Molinoff PB (eds) Basic Neurochemistry. Raven Press, New York, pp 181-208

    Google Scholar 

  • Felten DL, Felten SY, Carlson SL, Olschowka JA, Livnat S (1985) Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 135:S755–S765.

    Google Scholar 

  • Fink T, Weihe E (1988) Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation? Neurosci Lett 90:39–44

    PubMed  CAS  Google Scholar 

  • Fiore M, Angelucci F, Alleva E, Branchi I, Probert L, Aloe L (2000) Learning performances, brain NGF distribution and NPY levels in transgenic mice expressing TNFalpha. Behav Brain Res 112:165–175

    PubMed  CAS  Google Scholar 

  • Fried G, Terenius L, Hökfelt T, Goldstein M (1985) Evidence for differential localization of noradrenaline and neuropeptide Y in neuronal storage vesicles isolated from rat vas deferens. J Neurosci 5:450–458

    PubMed  CAS  Google Scholar 

  • Friedman EM, Irwin MR, Nonogaki K (1995) Neuropeptide Y inhibits in vivo specific antibody production in rats. Brain Behav Immun 9:182–189

    PubMed  CAS  Google Scholar 

  • Furukawa F (1997) Animal models of cutaneous lupus erythematosus and lupus erythematosus photosensitivity. Lupus 6:193–202

    PubMed  CAS  Google Scholar 

  • Gallai V, Sarchielli P, Firenze C, Trequattrini A, Paciaroni M, Usai F, Franceschini M, Palumbo R (1994) Neuropeptide Y plasma levels and serum dopamine-beta-hydroxylase activity in MS patients with and without abnormal cardiovascular reflexes. Acta Neurol Belg 94:44–52

    PubMed  CAS  Google Scholar 

  • Gehlert DR, Gackenheimer SL (1996) Unexpected high density of neuropeptide Y Y1 receptors in the guinea pig spleen. Peptides 17:1345–1348

    PubMed  CAS  Google Scholar 

  • Genain CP, Cannella B, Hauser SL, Raine CS (1999) Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nature Med 5:170–175

    PubMed  CAS  Google Scholar 

  • Gluck T, Oertel M, Reber T, Zietz B, Schölmerich J, Straub RH (2000) Altered function of the hypothalamic stress axes in patients with moderately active systemic lupus erythematosus. I. The hypothalamus-autonomic nervous system axis. J Rheumatol 27:903–910

    PubMed  CAS  Google Scholar 

  • Goebels N, Hofstetter H, Schmidt S, Brunner C, Wekerle H, Hohlfeld R (2000) Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence. Brain 123(3):508–518

    PubMed  Google Scholar 

  • Grau V, Scriba A, Stehling O, Steiniger B (2000) Monocytes in the rat. Immunobiology 202:94–103

    PubMed  CAS  Google Scholar 

  • Hafström I, Ringertz B, Lundeberg T, Palmblad J (1993) The effect of endothelin, neuropeptide Y, calcitonin gene-related peptide and substance P on neutrophil functions. Acta Physiol Scand 148:341–346

    PubMed  Google Scholar 

  • Hampton MB, Kettle AJ, Winterbourn CC (1998) Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92:3007–3017

    PubMed  CAS  Google Scholar 

  • Hauser GJ, Myers AK, Dayao EK, Zukowska-Grojec Z (1993) Neuropeptide Y infusion improves hemodynamics and survival in rat endotoxic shock. Am J Physiol 265:H1416–H1423

    PubMed  CAS  Google Scholar 

  • Hernanz A, Tato E, De la F M, de Miguel E, Arnalich F (1996) Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin and vasoactive intestinal peptide on interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha production by whole blood cells from healthy young and old subjects. J Neuroimmunol 71:25–30

    PubMed  CAS  Google Scholar 

  • Herzenberg LA (2000) B-l cells: the lineage question revisited. Immunol Rev 175:9–22

    PubMed  CAS  Google Scholar 

  • Higuchi T, Aiba Y, Nomura T, Matsuda J, Mochida K, Suzuki M, Kikutani H, Honjo T, Nishioka K, Tsubata T (2002) Cutting Edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease. J Immunol 168:9–12

    PubMed  CAS  Google Scholar 

  • Holmlund A, Ekblom A, Hansson P, Lind J, Lundeberg T, Theodorsson E (1991) Concentrations of neuropeptides substance P, neurokinin A, calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide in synovial fluid of the human temporomandibular joint. A correlation with symptoms, signs and arthroscopic findings. Int J Oral Maxillofac Surg 20:228–231

    PubMed  CAS  Google Scholar 

  • Hori T, Katafuchi T, Take S, Shimizu N, Niijima A (1995) The autonomic nervous system as a communication channel between the brain and the immune system. Neuroimmunomodulation 2:203–215

    PubMed  CAS  Google Scholar 

  • Hökfelt T (1991) Neuropeptides in perspective: the last ten years. Neuron 7:867–879

    PubMed  Google Scholar 

  • Huck S, Le Corre R, Youinou P, Zouali M (2001) Expression of B cell receptor-associated signaling molecules in human lupus. Autoimmunity 33:213–224

    PubMed  CAS  Google Scholar 

  • Irwin M, Daniels M, Bloom E T, Smith T L, Weiner H (1987) Life events, depressive symptoms, and immune function. Am J Psychiatry 144:437–441

    PubMed  CAS  Google Scholar 

  • Irwin M, Brown M, Patterson T, Hauger R, Mascovich A, Grant I (1991) Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress. FASEB J 5:3100–3107

    PubMed  CAS  Google Scholar 

  • Jacobs R, Pawlak CR, Mikeska E, Meyer-Olson D, Martin M, Heijnen CJ, Schedlowski M, Schmidt RE (2001) Systemic lupus erythematosus and rheumatoid arthritis patients differ from healthy controls in their cytokine pattern after stress exposure. Rheumatology (Oxford) 40:868–875

    CAS  Google Scholar 

  • Jarek MJ, Legare EJ, McDermott MT, Merenich JA, Kollef MH (1993) Endocrine profiles for outcome prediction from the intensive care unit. Crit Care Med 21:543–550

    PubMed  CAS  Google Scholar 

  • Jindal N, Hollenberg SM, Dellinger RP (2000) Pharmacologic issues in the management of septic shock. Crit Care Clin 16:233–249

    PubMed  CAS  Google Scholar 

  • Jones BM, Cheng IK, Wong RW, Kung AW (1993) CD5-positive and CD5-negative rheumatoid factor-secreting B cells in IgA nephropathy, rheumatoid arthritis and Graves’ disease. Scand J Immunol 38:575–580

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Katafuchi T, Ichijo T, Take S, Hori T (1993) Hypothalamic modulation of splenic natural killer cell activity in rats. J Physiol 471:209–221

    PubMed  CAS  Google Scholar 

  • Kawamura N, Tamura H, Obana S, Wenner M, Ishikawa T, Nakata A, Yamamoto H (1998) Differential effects of neuropeptides on cytokine production by mouse helper T cell subsets. Neuroimmunomodulation 5:9–15

    PubMed  CAS  Google Scholar 

  • Kiecolt-Glaser JK, Ricker D, George J, Messick G, Speicher CE, Garner W, Glaser R (1984) Urinary Cortisol levels, cellular immunocompetency, and loneliness in psychiatric inpatients. Psychosom Med 46:15–23

    PubMed  CAS  Google Scholar 

  • Kodukula K, Arcuri M, Cutrone JQ, Hugill RM, Lowe SE, Pirnik DM, Shu YZ, Fernandes PB, Seethala R (1995) BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, from Aspergillus niger WB2346. I. Taxonomy, fermentation, isolation and biological activity. J Antibiot (Tokyo) 48:1055–1059

    CAS  Google Scholar 

  • Kohm AP, Sanders VM (2001) Norepinephrine and Beta2-adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo. Pharmacol Rev 53:487–525

    PubMed  CAS  Google Scholar 

  • Konttinen YT, Hukkanen M, Kemppinen P, Segerberg M, Sorsa T, Malmstrom M, Rose S, Itescu S, Polak JM (1992) Peptide-containing nerves in labial salivary glands in Sjogren’s syndrome. Arthritis Rheum 35:815–820

    PubMed  CAS  Google Scholar 

  • Larsson J, Ekblom A, Henriksson K, Lundeberg T, Theodorsson E (1991) Concentration of substance P, neurokinin A, calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide in synovial fluid from knee joints in patients suffering from rheumatoid arthritis. Scand J Rheumatol 20:326–335

    PubMed  CAS  Google Scholar 

  • Lehmann D, Karussis D, Mizrachi-Koll R, Linde A S, Abramsky O (1997) Inhibition of the progression of multiple sclerosis by linomide is associated with upregulation of CD4+/CD45RA+ cells and downregulation of CD4+/CD45RO+ cells. Clin Immunol Immunopathol 85:202–209

    PubMed  CAS  Google Scholar 

  • Levine JD, Collier DH, Basbaum Al, Moskowitz MA, Helms CA (1985) Hypothesis: the nervous system may contribute to the pathophysiology of rheumatoid arthritis. J Rheumatol 12:406–411

    PubMed  CAS  Google Scholar 

  • Levite M (1998a) Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype. Proc Natl Acad Sci USA 95:12544–12549

    PubMed  CAS  Google Scholar 

  • Levite M, Cahalon L, Hershkoviz R, Steinman L, Lider O (1998b) Neuropeptides, via specific receptors, regulate Tcell adhesion to fibronectin. J Immunol 160:993–1000

    PubMed  CAS  Google Scholar 

  • Lorton D, Lubahn C, Klein N, Schaller J, Bellinger DL (1999) Dual role for noradrenergic innervation of lymphoid tissue and arthritic joints in adjuvant-induced arthritis. Brain Behav Immun 13:315–334

    PubMed  CAS  Google Scholar 

  • Lundberg JM, Saria A, Franco-Cereceda A, Theodorsson-Norheim E (1985) Mechanisms underlying changes in the contents of neuropeptide Y in cardiovascular nerves and adrenal gland induced by sympatholytic drugs. Acta Physiol Scand 124:603–611

    PubMed  CAS  Google Scholar 

  • Lundberg JM, Rudehill A, Sollevi A, Fried G, Wallin G (1989) Co-release of neuropeptide Y and noradrenaline from pig spleen in vivo: importance of subcellular storage, nerve impulse frequency and pattern, feedback regulation and resupply by axonal transport. Neuroscience 28:475–486

    PubMed  CAS  Google Scholar 

  • Lundberg JM (1996) Pharmacology of cotransmission in the autonomic nervous system: integrative aspects on amines, neuropeptides, adenosine triphosphate, amino acids and nitric oxide. Pharmacol Rev 48:113–178

    PubMed  CAS  Google Scholar 

  • Madden KS (2001) Catecholamines, sympathetic nerves, and immunity. In: Ader R, Felten DL, Cohen N (eds) Psychoneuroimmunology. Academic Press, San Diego, pp 197–230

    Google Scholar 

  • Maeda K, Yasuda M, Kaneda H, Maeda S, Yamadori A (1994) Cerebrospinal fluid (CSF) neuropeptide Y-and somatostatin-like immunoreactivities in man. Neuropeptides 27:323–332

    PubMed  CAS  Google Scholar 

  • Malfait AM, Malik AS, Marinova-Mutafchieva L, Butler DM, Maini RN, Feldmann M (1999) The beta2-adrenergic agonist salbutamol is a potent suppressor of established collagen-induced arthritis: mechanisms of action. J Immunol 162:6278–6283

    PubMed  CAS  Google Scholar 

  • Malmström RE, Hökfelt T, Bjorkman JA, Nihlen C, Bystrom M, Ekstrand AJ, Lundberg JM (1998) Characterization and molecular cloning of vascular neuropeptide Y receptor subtypes in pig and dog. Regul Pept 75/76:55–70

    Google Scholar 

  • Mapp PI, Kidd BL, Gibson SJ, Terry JM, Revell PA, Ibrahim NB, Blake DR, Polak JM (1990) Substance P-, calcitonin gene-related peptide-and c-flanking peptide of neuropeptide Y ir-fibers are present in normal synovium but depleted in patients with rheumatoid arthritis. Neuroscience 37:143–153

    PubMed  CAS  Google Scholar 

  • Medina S, Del Rio M, Hernanz A, de la Fuente M (2000) Age-related changes in the neuropeptide Y effects on murine lymphoproliferation and interleukin-2 production. Peptides 21:1403–1409

    PubMed  CAS  Google Scholar 

  • Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, Quirion R, Schwartz T, Westfall T (1998) XVI. International Union of Pharmacology recommend dations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev 50:143–150

    PubMed  CAS  Google Scholar 

  • Miles K, Quintans J, Chelmicka-Schorr E, Arnason BG (1981) The sympathetic nervous system modulates antibody response to thymus-independent antigens. J Neuroimmunol 1:101–105

    PubMed  CAS  Google Scholar 

  • Miller LE, Justen 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

    PubMed  CAS  Google Scholar 

  • Mitchell B, Kendall M, Adam E, Schumacher U (1997) Innervation of the thymus in normal and bone marrow reconstituted severe combined immunodeficient (SCID) mice. J Neuroimmunol 75:19–27

    PubMed  CAS  Google Scholar 

  • Mor A, Chartrel N, Vaudry H, Nicolas P (1994) Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity. Proc Natl Acad Sci USA 91:10295–10299

    PubMed  CAS  Google Scholar 

  • Nair MP, Schwartz SA, Wu K, Kronfol Z (1993) Effect of neuropeptide Y on natural killer activity of normal human lymphocytes. Brain Behav Immun 7:70–78

    PubMed  CAS  Google Scholar 

  • Nakajima A, Sendo W, Tsutsumino M, Koseki Y, Ichikawa N, Akama H, Taniguchi A, Terai C, Hara M, Kashiwazaki S (1998) Acute sympathetic hyperfunction in overlapping syndromes of systemic lupus erythematosus and polymyositis. J Rheumatol 25:1638–1641

    PubMed  CAS  Google Scholar 

  • Nawa H, Nakanishi S, Patterson PH (1991) Recombinant cholinergic differentiation factor (leukemia inhibitory factor) regulates sympathetic neuron phenotype by alterations in the size and amounts of neuropeptide mRNAs. J Neurochem 56:2147–2150

    PubMed  CAS  Google Scholar 

  • Neumann H, Medana I M, Bauer J, Lassmann H (2002) Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci 25:313–319

    PubMed  CAS  Google Scholar 

  • Nordenbo AM, Boesen F, Andersen EB (1989) Cardiovascular autonomic function in multiple sclerosis. J Auton Nerv Syst 26:77–84

    PubMed  CAS  Google Scholar 

  • Ohia SE, Jumblatt JE (1990) Inhibitory effects of neuropeptide Y on sympathetic neurotransmission in the rabbit iris-ciliary body. Neurochem Res 15:251–256

    PubMed  CAS  Google Scholar 

  • Panina-Bordignon P, Mazzeo D, Lucia PD, D’Ambrosio D, Lang R, Fabbri L, Self C, Sinigaglia F (1997) Beta2-agonists prevent Thl development by selective inhibition of interleukin 12. J Clin Invest 100:1513–1519

    PubMed  CAS  Google Scholar 

  • Parnet P, Kelley KW, Bluthe RM, Dantzer R (2002) Expression and regulation of interleukin-1 receptors in the brain. Role in cytokines-induced sickness behavior. J Neuroimmunol 125:5–14

    PubMed  CAS  Google Scholar 

  • Paul WE (1998) Fundamental Immunology, Lippincott-Raven, New York, p 245

    Google Scholar 

  • Pellieux C, Sauthier T, Domenighetti A, Marsh DJ, Palmiter RD, Brunner HR, Pedrazzini T (2000) Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors. Proc Natl Acad Sci USA 97:1595–1600

    PubMed  CAS  Google Scholar 

  • Pereira da Silva JA, Carmo-Fonseca M (1990) Peptide containing nerves in human synovium: immunohistochemical evidence for decreased innervation in rheumatoid arthritis. J Rheumatol 17:1592–1599

    PubMed  CAS  Google Scholar 

  • Petitto JM, Huang Z, McCarthy DB (1994) Molecular cloning of NPY-Y1 receptor cDNA from rat splenic lymphocytes: evidence of low levels of mRNA expression and [125I]NPY binding sites. J Neuroimmunol 54:81–86

    PubMed  CAS  Google Scholar 

  • Reder A, Checinski M, Chelmicka-Schorr E (1989) The effect of chemical sympathectomy on natural killer cells in mice. Brain Behav Immun 3:110–118

    PubMed  CAS  Google Scholar 

  • Romano TA, Felten SY, Felten DL, Olschowka J A (1991) Neuropeptide-Y innervation of the rat spleen: another potential immunomodulatory neuropeptide. Brain Behav Immun 5:116–131

    PubMed  CAS  Google Scholar 

  • Sawchenko PE, Swanson LW (1982) The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat. Brain Res 257:275–325

    PubMed  CAS  Google Scholar 

  • Schwarz H, Villiger PM, von Kempis J, Lotz M (1994) Neuropeptide Y is an inducible gene in the human immune system. J Neuroimmunol 51:53–61

    PubMed  CAS  Google Scholar 

  • Scriba A, Schneider M, Grau V, van der Meide P H, Steiniger B (1997) Rat monocytes upregulate NKR-P1A and down-modulate CD4 and CD43 during activation in vivo: monocyte subpopulations in normal and IFN-gamma-treated rats. J Leukoc Biol 62:741–752

    PubMed  CAS  Google Scholar 

  • Sellebjerg F, Jensen J, Jensen C V, Wiik A (2002) Expansion of CD5-B cells in multiple sclerosis correlates with CD80 (B7-1) expression. Scand J Immunol 56:101–107

    PubMed  CAS  Google Scholar 

  • Severn A, Rapson NT, Hunter CA, Liew FY (1992) Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J Immunol 148:3441–3445

    PubMed  CAS  Google Scholar 

  • Shen GH, Grundemar L, Zukowska-Grojec Z, Hakanson R, Wahlestedt C (1991) C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents. Eur J Pharmacol 204:249–256

    PubMed  CAS  Google Scholar 

  • Shimizu M, Shigeri Y, Tatsu Y, Yoshikawa S, Yumoto N (1998) Enhancement of antimicrobial activity of neuropeptide Y by N-terminal truncation. Antimicrob Agents Chemother 42:2745–2746

    PubMed  CAS  Google Scholar 

  • Soder O Hellström PM (1987) Neuropeptide regulation of human thymocyte, guinea pig T lymphocyte and rat B lymphocyte mitogenesis. Int Arch Allergy Appl Immunol 84:205–211

    PubMed  CAS  Google Scholar 

  • Song C Leonard B E (1998) Comparison between the effects of sigma receptor ligand JO 1784 and neuropeptide Y on immune functions. Eur J Pharmacol 345:79–87

    PubMed  CAS  Google Scholar 

  • Straub RH, Westermann J, Schölmerich J, Falk W (1998) Dialogue between the CNS and the immune system in lymphoid organs. Immunol Today 19:409–413

    PubMed  CAS  Google Scholar 

  • Straub RH, Schaller T, Miller LE, von Hörsten S, Jessop DS, Falk W, Schölmerich J (2000a) Neuropeptide Y cotransmission with norepinephrine in the sympathetic nerve-macrophage interplay. J Neurochem 75:2464–2471

    PubMed  CAS  Google Scholar 

  • Straub RH, Mayer M, Kreutz M, Leeb S, Schölmerich J, Falk W (2000b) Neurotransmitters of the sympathetic nerve terminal are powerful chemoattractants for monocytes. J Leukoc Biol 67:553–558

    PubMed  CAS  Google Scholar 

  • Straub RH, Herfarth H, Falk W, Andus T, Schölmerich J (2002) Uncoupling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis in inflammatory bowel disease? J Neuroimmunol 126:116–125

    PubMed  CAS  Google Scholar 

  • Sung CP, Arleth AJ, Feuerstein GZ (1991) Neuropeptide Y upregulates the adhesiveness of human endothelial cells for leukocytes. Circ Res 68:314–318

    PubMed  CAS  Google Scholar 

  • Tabarowski Z, Gibson-Berry K, Felten SY (1996) Noradrenergic and peptidergic innervation of the mouse femur bone marrow. Acta Histochem 98:453–457

    PubMed  CAS  Google Scholar 

  • Thyaga Rajan S, Felten SY, Felten DL (1998) Restoration of sympathetic noradrenergic nerve fibers in the spleen by low doses of L-deprenyl treatment in young sympathectomized and old Fischer 344 rats. J Neuroimmunol 81:144–157

    CAS  Google Scholar 

  • Turnbull AV Rivier CL (1999) Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79:1–71

    PubMed  CAS  Google Scholar 

  • van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF (1996) Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 97:713–719

    PubMed  Google Scholar 

  • van Roon JA, Lafeber FP, Bijlsma JW (2001) Synergistic activity of interleukin-4 and interleukin-10 in suppression of inflammation and joint destruction in rheumatoid arthritis. Arthritis Rheum 44:3–12

    PubMed  Google Scholar 

  • Vermeer LA, de Boer NK, Bucci C, Bos NA, Kroese FG, Alberti S (1994) MRC OX19 recognizes the rat CD5 surface glycoprotein, but does not provide evidence for a population of CD5bright B cells. Eur J Immunol 24:585–592

    PubMed  CAS  Google Scholar 

  • von Horsten S, Nave H, Ballof J, Helfritz F, Meyer D, Schmidt RE, Stalp M, Exton NG, Exton MS, Straub RH, Radulovic J, Pabst R (1998a) Centrally applied NPY mimics immunoactivation induced by non-analgesic doses of met-enkephalin. Neuroreport 9:3881–3885

    Google Scholar 

  • von Hörsten S, Ballof J, Helfritz F, Nave H, Meyer D, Schmidt RE, Stalp M, Klemm A, Tschernig T, Pabst R (1998b) Modulation of innate immune functions by intracerebroventricularly applied neuropeptide Y: dose and time dependent effects. Life Sci 63:909–922

    Google Scholar 

  • von Hörsten S, Exton NG, Exton MS, Helfritz F, Nave H, Ballof J, Stalp M, Pabst R (1998c) Brain NPY Y1 receptors rapidly mediate the behavioral response to novelty and a compartment-specific modulation of granulocyte function in blood and spleen. Brain Res 806:282–286

    Google Scholar 

  • Vouldoukis I, Shai Y, Nicolas P, Mor A (1996) Broad spectrum antibiotic activity of the skin-PYY. FEBS Lett 380:237–240

    PubMed  CAS  Google Scholar 

  • Wahlestedt C, Edvinsson L, Ekblad E, Hakanson R (1985) Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction: mode of action. J Pharmacol Exp Ther 234:735–741

    PubMed  CAS  Google Scholar 

  • Westermann J, Pabst R (1990) Lymphocyte subsets in the blood: a diagnostic window on the lymphoid system? Immunol Today 11:406–410

    PubMed  CAS  Google Scholar 

  • Westermann J, Michel S, Lopez-Kostka S, Bode U, Rothkötter HJ, Bette M, Weihe E, Straub RH, Pabst R (1998) Regeneration of implanted splenic tissue in the rat: re-innervation is host age-dependent and necessary for tissue development. J Neuroimmunol 88:67–76

    PubMed  CAS  Google Scholar 

  • Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schoning B, Glockner F, Lanksch WR, Volk HD, Docke WD (1998) Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nature Med 4:808–813

    PubMed  CAS  Google Scholar 

  • Xu Y Wiernik PH (2001) Systemic lupus erythematosus and B-cell hematologic neoplasm. Lupus 10:841–850

    PubMed  CAS  Google Scholar 

  • Yang D, Biragyn A, Kwak LW, Oppenheim JJ (2002) Mammalian defensins in immunity: more than just microbicidal. Trends Immunol 23:291–296

    PubMed  CAS  Google Scholar 

  • Yokota T, Matsunaga T, Okiyama R, Hirose K, Tanabe H, Furukawa T, Tsukagoshi H (1991) Sympathetic skin response in patients with multiple sclerosis compared with patients with spinal cord transection and normal controls. Brain 114(3):1381–1394

    PubMed  Google Scholar 

  • Zoukos Y, Thomaides T, Pavitt DV, Leonard JP, Cuzner ML, Mathias CJ (1992) Up-regulation of beta-adrenoceptors on circulating mononuclear cells after reduction of central sympathetic outflow by clonidine in normal subjects. Clin Auton Res 2:165–170

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Functional and Applied Anatomy, OE 4120, Carl-Neuberg Str. 1, 30625, Hannover, Germany

    S. Bedoui & R. Pabst

Authors
  1. S. Bedoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Pabst
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. von Hörsten
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Afd. Farmacologie & Farmacotherapie, Academisch Medisch Centrum, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    Martin C. Michel

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bedoui, S., Pabst, R., von Hörsten, S. (2004). NPY and Immune Functions: Implications for Health and Disease. In: Michel, M.C. (eds) Neuropeptide Y and Related Peptides. Handbook of Experimental Pharmacology, vol 162. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18764-3_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18764-3_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62282-3

  • Online ISBN: 978-3-642-18764-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation