Wiener Medizinische Wochenschrift

, Volume 160, Issue 5–6, pp 112–117

The vagal immune reflex: a blessing from above

Themenschwerpunkt

Summary

The innate immune response is activated upon recognition of infection or injury. A tight regulation of this inflammatory response is vital to ensure that it does not spin out of control and becomes harmful to the host. Recently, a neural circuit has been identified that controls the inflammatory response in a reflex-like manner. This circuit involves the vagus nerve which is able to sense inflammation and to respond to it by releasing acetylcholine which, through an interaction with immune cells, dampens the inflammatory response. The current knowledge regarding this "vagal immune reflex" is discussed with an emphasis on its role in sepsis.

Keywords

Vagus nerve Neuroimmunology Sepsis 

Der vagale Immunreflex

Zusammenfassung

Die angeborene Immunantwort wird bei Erkennen von Infektion oder Verletzung aktiviert. Eine kompakte Regulation dieser inflammatorischen Antwort ist vital, um die Kontrolle nicht zu verlieren und eine Gefahr für den Wirt darzustellen. Kürzlich wurde eine neurale Leitung identifiziert, die die inflammatorische Antwort in einer reflexhaften Art und Weise kontrolliert. Diese Leitung involviert den Vagusnerv, der imstande ist, eine Entzündung wahrzunehmen und durch Abgabe von Aetylcholin zu antworten, wodurch mittels Interaktion mit Immunzellen die Immunantwort gemildert wird. Das derzeitige Wissen bezüglich des "vagalen Immunreflexes" wird mit Betonung der Rolle in der Sepsis diskutiert.

Schlüsselwörter

Nervus vagus Neuroimmunologie Sepsis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Roth J, Harre EM, Rummel C, et al. Signaling the brain in systemic inflammation: role of sensory circumventricular organs. Front Biosci, 9: 290–300, 2004CrossRefPubMedGoogle Scholar
  2. Watkins LR, Maier SF. Immune regulation of central nervous system functions: from sickness responses to pathological pain. J Intern Med, 257: 139–155, 2005CrossRefPubMedGoogle Scholar
  3. Steinman L. Elaborate interactions between the immune and nervous systems. Nat Immunol, 5: 575–581, 2004CrossRefPubMedGoogle Scholar
  4. Fleshner M, Goehler LE, Schwartz BA, et al. Thermogenic and corticosterone responses to intravenous cytokines (IL-1beta and TNF-alpha) are attenuated by subdiaphragmatic vagotomy. J Neuroimmunol, 86: 134–141, 1998CrossRefPubMedGoogle Scholar
  5. Maier SF, Goehler LE, Fleshner M, et al. The role of the vagus nerve in cytokine-to-brain communication. Ann NY Acad Sci, 840: 289–300, 1998CrossRefPubMedGoogle Scholar
  6. Goehler LE, Relton JK, Dripps D, et al. Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication. Brain Res Bull, 43: 357–364, 1997CrossRefPubMedGoogle Scholar
  7. Felten DL, Felten SY. Sympathetic noradrenergic innervation of immune organs. Brain Behav Immun, 2: 293–300, 1988CrossRefPubMedGoogle Scholar
  8. Borovikova LV, Ivanova S, Zhang M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 405(6785): 458–462, 2000CrossRefPubMedGoogle Scholar
  9. Wang H, Yu M, Ochani M, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature, 421(6921): 384–388, 2003CrossRefPubMedGoogle Scholar
  10. van der Poll T. Effects of catecholamines on the Inflammatory response. Sepsis, 4: 159–167, 2000CrossRefGoogle Scholar
  11. Leceta J, Gomariz RP, Martinez C, et al. Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP. Ann NY Acad Sci, 921: 92–102, 2000PubMedCrossRefGoogle Scholar
  12. Steinman L, Conlon P, Maki R, et al. The intricate interplay among body weight, stress, and the immune response to friend or foe. J Clin Invest, 111: 183–185, 2003PubMedGoogle Scholar
  13. van Westerloo DJ, Giebelen IA, Florquin S, et al. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. Gastroenterology, 130: 1822–1830, 2006CrossRefPubMedGoogle Scholar
  14. van Westerloo DJ, Giebelen IA, Florquin S, et al. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis, 191: 2138–2148, 2005CrossRefPubMedGoogle Scholar
  15. Borovikova LV, Ivanova S, Nardi D, et al. Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation. Auton Neurosci, 85: 141–147, 2000CrossRefPubMedGoogle Scholar
  16. Giebelen IA, van Westerloo DJ, LaRosa GJ, et al. Local stimulation of alpha7 cholinergic receptors inhibits LPS-induced TNF-alpha release in the mouse lung. Shock, 28: 700–703, 2007PubMedGoogle Scholar
  17. Giebelen IA, van Westerloo DJ, LaRosa GJ, et al. Stimulation of alpha7 cholinergic receptors inhibits lipopolysaccharide-induced neutrophil recruitment by a tumor necrosis factor alpha-independent mechanism. Shock, 27: 443–447, 2007CrossRefPubMedGoogle Scholar
  18. Yoshikawa H, Kurokawa M, Ozaki N, et al. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol, 146: 116–123, 2006CrossRefPubMedGoogle Scholar
  19. de Jonge WJ, van der Zanden EP, The FO, et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol, 6: 844–851, 2005CrossRefPubMedGoogle Scholar
  20. Huston JM, Ochani M, Rosas-Ballina M, et al. Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med, 203: 1623–1628, 2006CrossRefPubMedGoogle Scholar
  21. 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, 105: 11008–11013, 2008CrossRefPubMedGoogle Scholar
  22. Tracey KJ. Reflex control of immunity. Nat Rev Immunol, 9: 418–428, 2009CrossRefPubMedGoogle Scholar
  23. Pontet J, Contreras P, Curbelo A, et al. Heart rate variability as early marker of multiple organ dysfunction syndrome in septic patients. J Crit Care, 18: 156–163, 2003CrossRefPubMedGoogle Scholar
  24. George MS, Rush AJ, Sackeim HA, et al. Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders. Int J Neuropsychopharmacol, 6: 73–83, 2003CrossRefPubMedGoogle Scholar
  25. George MS, Nahas Z, Bohning DE, et al. Vagus nerve stimulation therapy: a research update. Neurology, 59(6 Suppl 4): S56–S61, 2002PubMedGoogle Scholar
  26. Marangell LB, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes. Biol Psychiat, 51: 280–287, 2002CrossRefPubMedGoogle Scholar
  27. Sackeim HA, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology, 25: 713–728, 2001CrossRefPubMedGoogle Scholar
  28. Ben Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol, 1: 477–482, 2002CrossRefPubMedGoogle Scholar
  29. Huston JM, Gallowitsch-Puerta M, Ochani M, et al. Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med, 35: 2762–2768, 2007CrossRefPubMedGoogle Scholar
  30. Ulloa L, Tracey KJ. The "cytokine profile": a code for sepsis. Trends Mol Med, 11: 56–63, 2005CrossRefPubMedGoogle Scholar
  31. Zheng H, Wei DQ, Zhang R, et al. Screening for new agonists against Alzheimer's disease. Med Chem, 3: 488–493, 2007CrossRefPubMedGoogle Scholar
  32. Arai I, Hirose H, Muramatsu M, et al. Possible involvement of non-steroidal anti-inflammatory drugs in vagal-mediated gastric acid secretion in rats. Jpn J Pharmacol, 37: 91–99, 1985CrossRefPubMedGoogle Scholar
  33. Pavlov VA, Parrish WR, Rosas-Ballina M, et al. Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Brain Behav Immun, 23: 41–45, 2009CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Academic Medical Center, Department of Intensive CareUniversity of AmsterdamAmsterdamThe Netherlands

Personalised recommendations