Download PDF
Aktuelle Rheumatologie 2013; 38(04): 241-246
DOI: 10.1055/s-0033-1351305
Übersichtsarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Änderungen des autonomen Nervensystems bei rheumatoider Arthritis

Changes of Autonomic Nervous System in Rheumatoid Arthritis
O. Malysheva
1   Sektion Rheumatologie, Universitätsklinikum Leipzig
,
A. Esber
1   Sektion Rheumatologie, Universitätsklinikum Leipzig
,
G. C. O. Baerwald
1   Sektion Rheumatologie, Universitätsklinikum Leipzig
› Author Affiliations
Further Information

Publication History

Publication Date:
09 August 2013 (online)

Also available at
    Permissions and Reprints

Zusammungfassung

Die rheumatoide Arthritis (RA) ist eine chronische Erkrankung, deren Auslöser und Verlaufsfaktoren noch nicht vollends geklärt sind. Durch intensive Forschung ist bisher bekannt, dass vielmehr verschiedene Faktoren an der Entstehung einer entzündlichen Rheumaerkrankung beteiligt sind. Doch neben genetischen Faktoren scheinen auch eine Dysregulation neuroimmunologischer Interaktionen, insbesondere Änderungen des autonomen Nervensystems (ANS) bei der Entstehung der Krankheit eine Rolle zu spielen. Aus Studien kann man entnehmen, dass das ANS auf die Krankheitsaktivität der RA Einfluss nehmen und das Risiko für Herzkreislauferkrankungen und Mortalität erhöhen kann. Die autonome Aktivität der RA-Patienten in Ruhe ist durch eine signifikant erhöhte Herzfrequenz, ein Überwiegen des Sympathikus im Verhältnis zum Parasympathikus sowie eine signifikant ernie­drigte Parasympathikusaktivität gekennzeichnet. Die Stressantwort der Patienten ist häufig pathologisch und durch signifikante Hypoaktivität des Sympathikus und Hyporeaktivität des Parasympathikus charakterisiert. Die Studienlage zeigt die klinische Relevanz einer autonomen Dysregulation bei RA, für ein besseres Verständnis sind jedoch noch weitere klinische und experimentelle Untersuchungen des ANS bei RA notwendig.

Abstract

Rheumatoid arthritis (RA) is a chronic rheumatic disease of unknown aetiology and variable severity. It is now well known that several risk factors are involved in its pathogenesis, e. g., genetic as well as environmental factors, including a distortion of the neuro-immune interaction. A modulation of autonomic nervous system (ANS) function is suggested to play an important role in the pathogenesis of RA. Many studies have clearly shown that ANS dysregulation is associated with an elevated risk of cardiovascular disease leading to an increased mortality in RA. Disturbed function of ANS in RA patients is characterised by an increased heart rate and a prevalence of sympathetic over parasympathetic activity. However, more studies are warranted to further explore the pathophysiological implications of ANS function on onset and activity of chronic autoimmune diseases.

Schlüsselwörter

autonomes Nervensystem - rheumatoide Arthritis - Sympathikus - Parasympathikus - Krankheitsaktivität

Key words

autonomic nervous system - rheumatoid arthritis - sympathetic activity - parasympathetic activity - disease activity
 

  • Literatur

  • 1 Aletaha D, Neogi T, Silman AJ et al. Rheumatoid arthritis classificationcriteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62: 2569-2581
    Google Scholar
  • 2 Østensen M, Villiger PM, Förger F. Interaction of pregnancy and autoimmune rheumatic disease. Autoimmun Rev 2012; 11: A437-A446
    CrossrefPubMedGoogle Scholar
  • 3 Bax M, van Heemst J, Huizinga TWJ et al. Genetics of rheumatoid arthritis: what have we learned?. Immunogenetics 2011; 63: 459-466
    CrossrefPubMedGoogle Scholar
  • 4 Malysheva O, Pierer M, Wagner U et al. Stress und Rheuma. Z Rheumatol 2010; 69: 539-543
    CrossrefPubMedGoogle Scholar
  • 5 Straub RH, Fassold A. Neuroendokrin-immune Interaktionen bei rheumatischen Krankheiten. Z Rheumatol 2010; 69: 340-348
    CrossrefPubMedGoogle Scholar
  • 6 Del Rey A, Wolff C, Wildmann J et al. When immune-neuro-endocrine interactions are disrupted: experimentally induced arthritis as an example. Neuroimmunomodulation 2010; 17: 165-168
    CrossrefPubMedGoogle Scholar
  • 7 Koopman F, Stoof S. Restoring the balance of the autonomic nervous system as an innovative approach to the treatment of rheumatoid arthritis. Mol Med 2011; 17: 937-948
    PubMedGoogle Scholar
  • 8 Kalamida D, Poulas K, Avramopoulou V et al. Muscle and neuronal nicotinic acetylcholine receptors. FEBS Journal 2007; 274: 3799-3845
    CrossrefPubMedGoogle Scholar
  • 9 Nance DM, Sanders VM. Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 2007; 21: 736-745
    CrossrefPubMedGoogle Scholar
  • 10 Buijs RM, van der Vliet J, Garidou ML et al. Spleen Vagal Denervation Inhibits the Production of Antibodies to Circulating Antigens. PLoS ONE 2008; 3: e3152
    CrossrefPubMedGoogle Scholar
  • 11 Rosas-Ballina M, Ochani M, Parrish WR et al. Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci USA 2008; 105: 11008-11013
    CrossrefPubMedGoogle Scholar
  • 12 Wang H, Yu M, Ochani M et al. Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature 2002; 421: 384-388
    PubMedGoogle Scholar
  • 13 Tracey KJ, Borovikova LV, Ivanova S et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405: 458-462
    CrossrefPubMedGoogle Scholar
  • 14 Saeed RW. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med 2005; 201: 1113-1123
    CrossrefPubMedGoogle Scholar
  • 15 Bernik TR. Pharmacological Stimulation of the Cholinergic Antiinflammatory Pathway. J Exp Med 2002; 195: 781-788
    CrossrefPubMedGoogle Scholar
  • 16 Felten DL, Felten SY, Bellinger DL et al. Noradrenergic sympathetic neural interactions with the immune system: structure and function. Immunol Rev 1987; 100: 225-260
    CrossrefPubMedGoogle Scholar
  • 17 Viswanathan K, Dhabhar FS. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation. Proc Natl Acad Sci USA 2005; 102: 5808-5813
    CrossrefPubMedGoogle Scholar
  • 18 Elenkov IJ, Wilder RL, Chrousos GP et al. The sympathetic nerve- an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000; 52: 595-638
    PubMedGoogle Scholar
  • 19 Xu BY, Ärlehag L, Rantapää-Dahlquist SB et al. 2 Adrenoceptor gene single nucleotide polymorphisms are associated with rheumatoid arthritis in northern Sweden. Ann Rheum Dis 2005; 64: 773-776
    CrossrefPubMedGoogle Scholar
  • 20 Wahle M, Krause A, Pierer M et al. Immunopathogenesis of Rheumatic Diseases in the Context of Neuroendocrine Interactions. Ann N Y Acad Sci 2002; 966: 355-364
    CrossrefPubMedGoogle Scholar
  • 21 Krause A, Henrich A, Beckh KH et al. 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 1992; 22: 47-51
    PubMedGoogle Scholar
  • 22 Green SA, Turki J, Hall IP et al. Implications of genetic variability of human beta 2-adrenergic receptor structure. Pulm Pharmacol 1995; 8: 1-10
    CrossrefPubMedGoogle Scholar
  • 23 Malysheva O, Pierer M, Wagner U et al. Association between 2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope. Ann Rheum Dis 2008; 67: 1759-1764
    CrossrefPubMedGoogle Scholar
  • 24 Chong LK, Chowdry J, Ghahramani P et al. Influence of genetic polymorphisms in the beta2-adrenoceptor on desensitization in human lung mast cells. Pharmacogenetics 2000; 10: 153-162
    CrossrefPubMedGoogle Scholar
  • 25 Baerwald CG, Burmester GR, Krause A. Interactions of autonomic nervous, neuroendocrine and immune systems in rheumatoid arthritis. Rheum Dis Clin North Am 2000; 26: 841-857
    CrossrefPubMedGoogle Scholar
  • 26 Miller LE, Grifka J, Schölmerich J et al. Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritis. J Rheumatol 2002; 29: 427-435
    PubMedGoogle Scholar
  • 27 Straub RH, Dhabhar FS, Bijlsma JW et al. How psychological stress via hormones and nerve fibers may exacerbate rheumatoid arthritis. Arthritis Rheum 2005; 52: 16-26
    CrossrefPubMedGoogle Scholar
  • 28 Selye H. The story of the adaptation syndrome. Acta Inc; Montreal: 1952
    Google Scholar
  • 29 Stojanovich L. Autonomic dysfunction in autoimmune rheumatic disease. Autoimmun Rev 2009; 8: 569-572
    CrossrefPubMedGoogle Scholar
  • 30 Crousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol 2009; 5: 374-381
    CrossrefPubMedGoogle Scholar
  • 31 Zautra AJ, Hoffman J, Potter P et al. Examination of changes in interpersonal stress as a factor in disease exacerbations among women with rheumatoid arthritis. Ann Behav Med 1997; 19: 279-286
    CrossrefPubMedGoogle Scholar
  • 32 Feigenbaum SL, Masi AT, Kaplan SB. Prognosis in rheumatoid arthritis. A longitudinal study of newly diagnosed younger adult patients. Am J Med 1979; 66: 377-384
    CrossrefPubMedGoogle Scholar
  • 33 van der Roupe Voort C, Heijnen CJ, Wulffraat N et al. 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 2000; 110: 223-229
    CrossrefPubMedGoogle Scholar
  • 34 Hirano D, Nagashima M, Ogawa R et al. Serum levels of interleukin 6 and stress related substances indicate mental stress condition in patients with rheumatoid arthritis. J Rheumatol 2001; 28: 490-495
    PubMedGoogle Scholar
  • 35 Kittner JM, Jacobs RPCR, Heijnen CJ et al. Adrenaline-induced immunological changes are altered in patients with rheumatoid arthritis. Rheumatology (Oxford) 2002; 41: 1031-1039
    CrossrefPubMedGoogle Scholar
  • 36 Evrengül H, Dursunoglu D, Cobankara V et al. Heart rate variability in patients with rheumatoid arthritis. Rheumatol Int 2003; 24: 198-202
    PubMedGoogle Scholar
  • 37 Dekkers JC, Geenen R, Evers AW et al. Biopsychosocial mediators and moderators of stress-health relationships in patients with recently diagnosed rheumatoid arthritis. Arthritis Rheum 2001; 45: 307-316
    CrossrefPubMedGoogle Scholar
  • 38 Leden I, Eriksson A, Lilja B et al. Autonomic nerve function in rheumatoid arthritis of varying severity. Scand J Rheumatol 1983; 12: 166-170
    CrossrefPubMedGoogle Scholar
  • 39 Toussirot E, Serratrice G, Valentin P. Autonomic nervous system involvement in rheumatoid arthritis. 50 cases. J Rheumatol 1993; 20: 1508-1514
    PubMedGoogle Scholar
  • 40 Kuis W, van Jong-de Vos Steenwijk CCE, Sinnema G et al. The Autonomic Nervous System and the Immune System in Juvenile Rheumatoid Arthritis. Brain Behav Immun 1996; 10: 387-398
    CrossrefPubMedGoogle Scholar
  • 41 Kao T, Hsiao HC, Chiu HW, Kong CW. The relationship of late potentials to assessment of heart rate variability in post-infarction patients. Int J Cardiol 2000; 74: 207-214
    CrossrefPubMedGoogle Scholar
  • 42 Kvalvik AG, Jones MA, Symmons DP. Mortality in a cohort of Norwegian patients with rheumatoid arthritis followed from 1977 to 1992. Scand J Rheumatol 2000; 29: 29-37
    CrossrefPubMedGoogle Scholar
  • 43 Riise T, Jacobsen BK, Gran JT et al. Total mortality is increased in rheumatoid arthritis. A 17-year prospective study. Clin Rheumatol 2001; 20: 123-127
    CrossrefPubMedGoogle Scholar
  • 44 Illigens BM, Gibbons CH. Sweat testing to evaluate autonomic function. Clin Auton Res 2009; 19: 79-87
    CrossrefPubMedGoogle Scholar
  • 45 Benett PH, Scott JT. Autonomic neuropathy in rheumatoid arthritis. Ann Rheum Dis 1965; 24: 161-168
    CrossrefPubMedGoogle Scholar