Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture-Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial

Neuromodulation

Volumn 19, Issue 3, 2016, Pages 283-291

  Lerman, Imanuel ^a,b,c,d   Hauger, Richard ^a,b,d   Sorkin, Linda ^c   Proudfoot, James ^c   Davis, Bryan ^c   Huang, Andy ^c   Lam, Katie ^c   Simon, Bruce ^e   Baker, Dewleen G ^a,b,d  

^a Center of Excellence for Stress and Mental Health   (United States)

^b VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^c University of California at San Diego   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e Electrocore Research Unit   (United States)

Author keywords

Cholinergic anti inflammatory pathway; immunomodulation; neuromodulation; vagus nerve stimulation

Indexed keywords

CHEMOKINE; CYTOKINE; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MONOCYTE CHEMOTACTIC PROTEIN 1; TUMOR NECROSIS FACTOR; LIPOPOLYSACCHARIDE;

ADULT; ARTICLE; BLOOD CULTURE; CONTROLLED STUDY; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; IMMUNOMODULATION; MALE; NERVE STIMULATOR; NONINVASIVE TRANSCUTANEOUS VAGUS NERVE STIMULATION; NORMAL HUMAN; PAIN; PILOT STUDY; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; THERAPY EFFECT; VAGUS NERVE STIMULATION; ADOLESCENT; BLOOD; BLOOD CELL; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DOWN REGULATION; DRUG EFFECTS; INNERVATION; MIDDLE AGED; NONPARAMETRIC TEST; PHYSIOLOGY; PROCEDURES; SKIN; TIME FACTOR; YOUNG ADULT;

ADOLESCENT; ADULT; BLOOD CELLS; BLOOD CULTURE; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DOWN-REGULATION; FEMALE; HEALTHY VOLUNTEERS; HUMANS; LIPOPOLYSACCHARIDES; MALE; MIDDLE AGED; PILOT PROJECTS; SKIN; STATISTICS, NONPARAMETRIC; TIME FACTORS; VAGUS NERVE STIMULATION; YOUNG ADULT;

EID: 84962531633     PISSN: 10947159     EISSN: 15251403     Source Type: Journal    
DOI: 10.1111/ner.12398     Document Type: Article

References (62)

1. Tracey KJ., Reflex control of immunity. Nat Rev Immunol 2009; 9: 418-428.
2. Tracey KJ., The inflammatory reflex. Nature 2002; 420: 853-859.
3. Andersson U, Tracey KJ., Reflex principles of immunological homeostasis. Annu Rev Immunol 2012; 30: 313-335.
4. Gierut A, Perlman H, Pope RM., Innate immunity and rheumatoid arthritis. Rheum Dis Clin North Am 2010; 36: 271-296.
5. Maciejewska Rodrigues H, Jüngel A, Gay RE, Gay S., Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis. Mol Immunol 2009; 47: 12-18.
6. Bachelez H., Immunopathogenesis of psoriasis: recent insights on the role of adaptive and innate immunity. J Autoimmun 2005; 25 (Suppl.): 69-73.
7. Bruchfeld A, Goldstein RS, Chavan S, et al., Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis. J Intern Med 2010; 268: 94-101.
8. Koopman FA, Schuurman PR, Vervoordeldonk MJ, et al., Vagus nerve stimulation: a new bioelectronics approach to treat rheumatoid arthritis? Best Pract Res Clin Rheumatol 2014; 28: 625-635.
9. Levine YA, Koopman FA, Faltys M, et al., Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. PLoS One 2014; 9: e104530.
10. Baker DG, Nievergelt CM, O'Connor DT., Biomarkers of PTSD: neuropeptides and immune signaling. Neuropharmacology 2012; 62: 663-673.
11. Breen MS, Maihofer AX, Glatt SJ, et al., Gene networks specific for innate immunity define post-traumatic stress disorder. Mol Psychiatry 2015; 20: 1538-1545.
12. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW., From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2010; 9: 46-56.
13. Straub RH, Paimela L, Peltomaa R, Schölmerich J, Leirisalo-Repo M., Inadequately low serum levels of steroid hormones in relation to IL-6 and tumor necrosis factor in untreated patients with early rheumatoid arthritis and reactive arthritis. Arthritis Rheum 2002; 46: 654-662.
14. Straub R., Origin of typical disease sequelae: circadian rhythms of symptoms. The origin of chronic inflammatory systemic diseases and their sequelae. Waltham, MA: Elsevier Inc., 2015: 225-227.
15. Crofford LJ, Kalogeras KT, Mastorakos G, et al., Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab 1997; 82: 1279-1283.
16. Koopman FA, Stoof SP, Straub RH, Van Maanen MA, Vervoordeldonk MJ, Tak PP., Restoring the balance of the autonomic nervous system as an innovative approach to the treatment of rheumatoid arthritis. Mol Med 2011; 17: 937-948.
17. Baccala R, Gonzalez-Quintial R, Lawson BR, et al., Sensors of the innate immune system: their mode of action. Nat Rev Rheumatol 2009; 5: 448-456.
18. Chen GY, Nuñez G., Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol 2010; 10: 826-837.
19. Andersson U, Tracey KJ., HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol 2011; 29: 139-162.
20. Goehler LE, Gaykema RP, Hansen MK, Anderson K, Maier SF, Watkins LR., Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci 2000; 85: 49-59.
21. Goehler LE, Gaykema RP, Nguyen KT, et al., Interleukin-1beta in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems? J Neurosci 1999; 19: 2799-2806.
22. Ek M, Kurosawa M, Lundeberg T, Ericsson A., Activation of vagal afferents after intravenous injection of interleukin-1β: role of endogenous prostaglandins. J Neurosci 1998; 18: 9471-9479.
23. Sternberg EM., Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat Rev Immunol 2006; 6: 318-328.
24. Watkins LR, Maier SF., Implications of immune-to-brain communication for sickness and pain. Proc Natl Acad Sci USA 1999; 96: 7710-7713.
25. Medzhitov R., Inflammation 2010: new adventures of an old flame. Cell 2010; 140: 771-776.
26. Chavan SS, Robbiati S, Steinberg BE, et al., Tumor necrosis factor induces specific neurograms in the sensory vagus nerve [abstract]. Presented at Society of Neuroscience Neuroscience 2014. Washington, DC, 2015. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3527&sKey=7ce6178f-43ee-41f3-8eda-f0dbce9afaa1&cKey=135933ff-fb59-4c3e-b1bc-25d1d597f8f7&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
27. Niijima A., The afferent discharges from sensors for interleukin 1 beta in the hepatoportal system in the anesthetized rat. J Auton Nerv Syst 1996; 61: 287-291.
28. Martelli D, McKinley MJ, McAllen RM., The cholinergic anti-inflammatory pathway: a critical review. Auton Neurosci 2014; 182: 65-69. doi: 10.1016/j.autneu.2013.12.007.
29. Bratton BO, Martelli D, McKinley MJ, Trevaks D, Anderson CR, McAllen RM., Neural regulation of inflammation: no neural connection from the vagus to splenic sympathetic neurons. Exp Physiol 2012; 97 (11): 1180-1185. doi: 10.1113/expphysiol.2011.061531.
30. Vida G, Peña G, Deitch EA, Ulloa L., Î'7-cholinergic receptor mediates vagal induction of splenic norepinephrine. J Immunol 2011; 186 (7): 4340-4346. doi: 10.4049/jimmunol.1003722.
31. Rosas-Ballina M, Olofsson PS, Ochani M, et al., Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 2011; 334 (6052): 98-101. doi: 10.1126/science.1209985.
32. Wang H, Yu M, Ochani M, et al., Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 2003; 421: 384-388.
33. Wang H, Liao H, Ochani M, et al., Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 2004; 10: 1216-1221.
34. Borovikova LV, Ivanova S, Zhang M, et al., Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405: 458-462.
35. Saeed RW, Varma S, Peng-Nemeroff T, et al., Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med 2005; 201: 1113-1123.
36. Parrish WR, Rosas-Ballina M, Gallowitsch-Puerta M, et al., Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling. Mol Med 2008; 14: 567-574.
37. Pavlov VA, Ochani M, Yang LH, et al., Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med 2007; 35: 1139-1144.
38. Hamano R, Takahashi HK, Iwagaki H, Yoshino T, Nishibori M, Tanaka N., Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes. Shock 2006; 26: 358-364.
39. Huston JM, Rosas-Ballina M, Xue X, et al., Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b. J Immunol 2009; 183: 552-559. doi: 10.4049/jimmunol.0802684.
40. Lu B, Kwan K, Levine YA, et al., Alpha7 nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release. Mol Med 2014; 20: 350-358.
41. Fernandez R, Acuña-Castillo C., Neural reflex control of inflammation during sepsis syndromes. In:, Azevdeo L, ed. Sepsis-an ongoing and significant challenge. 2012: 133-156. http://www.intechopen.com/books/sepsis-an-ongoing-and-significant-challenge/neural-reflex-control-of-inflammation-during-sepsis-syndromes
42. Silverman MN, Pearce BD, Biron CA, Miller AH., Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunol 2005; 18: 41-78.
43. Elenkov IJ, Tezzoni DG, Daly A, Harris AG, Chrousos GP., Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 2005; 12: 255-269.
44. McEwen BS., Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 2007; 87: 873-904.
45. Raison CL, Miller AH., When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry 2003; 160: 1554-1565.
46. Buske-Kirschbaum A., Cortisol responses to stress in allergic children: interaction with the immune response. Neuroimmunomodulation 2009; 16: 325-332.
47. Chrousos GP, Kino T., Glucocorticoid signaling in the cell. Expanding clinical implications to complex human behavioral and somatic disorders. Ann N Y Acad Sci 2009; 1179: 153-166.
48. Crofford LJ, Kalogeras KT, Mastorakos G, et al., Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab 1997; 82: 1279-1283.
49. Priftis KN, Papadimitriou A, Nicolaidou P, Chrousos GP., Dysregulation of the stress response in asthmatic children. Allergy 2009; 64: 18-31.
50. Olofsson PS., A stimulating concept: bioelectronic medicine in inflammatory disease. Bioelectron Med 2014; 1: 30-33.
51. Zhao YX, He W, Jing XH, et al., Transcutaneous auricular vagus nerve stimulation protects endotoxemic rat from lipopolysaccharide-induced inflammation. Evid Based Complement Alternat Med 2012; 2012: 627023. doi: 10.1155/2012/627023.
52. Koopman FA, Miljko S, Grazio S, et al., Pilot study of stimulation of the cholinergic anti-inflammatory pathway with an implantable vagus nerve stimulation device in patients with rheumatoid arthritis [abstract]. Arthritis Rheum 2012; 64 (Suppl. 10): 451.
53. Zitnik RJ., Treatment of chronic inflammatory diseases with implantable medical devices. Cleve Clin J Med 2011; 78 (Suppl. 1): S30-S34.
54. Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ., The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 2003; 9: 125-134.
55. Rosas-Ballina M, Ochani M, Parrish WR., Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci USA 2008; 105: 11008-11013.
56. Chowdhury F, Williams A, Johnson P., Validation and comparison of two multiplex technologies, Luminex and Mesoscale discovery, for human cytokine profiling. J Immunol Methods 2009; 340: 55-64.
57. Zhang Y, Popovic ZB, Bibevski S, et al., Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model. Circ Heart Fail 2009; 2: 692-699.
58. Scheiermann C, Kunisaki Y, Frenette PS., Circadian control of the immune system. Nat Rev Immunol 2013; 13: 190-198.
59. Haus E., Chronobiology of the immune system. In: Committee on Military Nutrition Research, Food and Nutrition Board, Institute of Medicine, ed. Military strategies for sustainment of nutrition and immune function in the field. Washington, DC: National Academy Press, 1999: 437-496. http://books.google.com/books?id=V-ZjKmO24ooC&pgis=1
60. Sabat R, Grütz G, Warszawska K, et al., Biology of interleukin-10. Cytokine Growth Factor Rev 2010; 21: 331-344.
61. Murray PJ., The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription. Proc Natl Acad Sci USA 2005; 102: 8686-8691. doi: 10.1073/pnas.0500419102.
62. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE., Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209-1220.