Cholinergic control of inflammation

Journal of Internal Medicine

Volumn 265, Issue 6, 2009, Pages 663-679

  Rosas Ballina, M ^a   Tracey, K J ^a  

^a FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH   (United States)

Author keywords

Alpha7; Cholinergic; Inflammation; Innate immunity

Indexed keywords

3 (2,4 DIMETHOXYBENZYLIDENE)ANABASEINE; ACETYLCHOLINE; ACETYLCHOLINESTERASE; AR R17779; ATROPINE; ATROPINE METHYL BROMIDE; BUNGAROTOXIN RECEPTOR; CAP 55; CHLORISONDAMINE; CHOLINE; HEXAMETHONIUM; JANUS KINASE 2; NEOSTIGMINE; NICOTINE; NICOTINIC AGENT; PHYSOSTIGMINE; STAT3 PROTEIN; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; CLINICAL TRIAL; CONFERENCE PAPER; CYTOKINE PRODUCTION; ENDOTHELIUM CELL; ENDOTOXEMIA; ENTERITIS; ENZYME ACTIVITY; HEART MUSCLE ISCHEMIA; HEMORRHAGIC SHOCK; HUMAN; ILEUS; INFLAMMATION; INNATE IMMUNITY; ISCHEMIA; KIDNEY DYSFUNCTION; KIDNEY ISCHEMIA; NONHUMAN; PANCREATITIS; PARASYMPATHETIC INNERVATION; PRIORITY JOURNAL; REPERFUSION INJURY; SEPSIS; SEPTIC SHOCK; SHOCK; ULCERATIVE COLITIS; UNSPECIFIED SIDE EFFECT; VAGUS NERVE;

ACETYLCHOLINE; ANIMALS; BRAIN; CHOLINERGIC AGENTS; INFLAMMATION; MICE; MICE, KNOCKOUT; NEURAL PATHWAYS; RECEPTORS, CHOLINERGIC; RECEPTORS, NICOTINIC; SEPSIS; TUMOR NECROSIS FACTOR-ALPHA; VAGUS NERVE;

EID: 66149103723     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/j.1365-2796.2009.02098.x     Document Type: Conference Paper

References (124)

1. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005 6 : 1191 7. (Pubitemid 43045627)
2. Riedemann NC, Guo RF, Ward PA. Novel strategies for the treatment of sepsis. Nat Med 2003 9 : 517 24. (Pubitemid 36597096)
3. Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 2003 3 : 791 800. (Pubitemid 37328657)
4. Qin S, Wang H, Yuan R et al. Role of HMGB1 in apoptosis-mediated sepsis lethality. J Exp Med 2006 203 : 1637 42. (Pubitemid 44036267)
5. Wang H, Bloom O, Zhang M et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999 285 : 248 51. (Pubitemid 29329996)
6. Agostoni E, Chinnock JE, De Daly MB, Murray JG. Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J Physiol 1957 135 : 182 205.
7. Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci 2000 85 : 1 17.
8. Goehler LE, Gaykema RP, Hammack SE, Maier SF, Watkins LR. Interleukin-1 induces c-Fos immunoreactivity in primary afferent neurons of the vagus nerve. Brain Res 1998 804 : 306 10. (Pubitemid 28496634)
9. 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 1997 43 : 357 64. (Pubitemid 27282130)
10. Maier SF, Goehler LE, Fleshner M, Watkins LR. The role of the vagus nerve in cytokine-to-brain communication. Ann N Y Acad Sci 1998 840 : 289 300. (Pubitemid 28302056)
11. Blalock JE. The immune system as a sensory organ. J Immunol 1984 132 : 1067 70.
12. Blalock JE. The immune system as the sixth sense. J Intern Med 2005 257 : 126 38. (Pubitemid 40193963)
13. Mascarucci P, Perego C, Terrazzino S, De Simoni MG. Glutamate release in the nucleus tractus solitarius induced by peripheral lipopolysaccharide and interleukin-1 beta. Neuroscience 1998 86 : 1285 90. (Pubitemid 28318552)
14. Tracey KJ. The inflammatory reflex. Nature 2002 420 : 853 9. (Pubitemid 36019638)
15. Borovikova LV, Ivanova S, Zhang M et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000 405 : 458 62. (Pubitemid 30367422)
16. Wang H, Yu M, Ochani M et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 2003 421 : 384 8. (Pubitemid 36157937)
17. 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 2007 35 : 2762 8. (Pubitemid 350175773)
18. Pavlov VA, Ochani M, Gallowitsch-Puerta M et al. Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci USA 2006 103 : 5219 23.
19. Huston JM, Ochani M, Rosas-Ballina M et al. Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med 2006 203 : 1623 8. (Pubitemid 44036265)
20. Mignini F, Streccioni V, Amenta F. Autonomic innervation of immune organs and neuroimmune modulation. Auton Autacoid Pharmacol 2003 23 : 1 25. (Pubitemid 36917752)
21. Berthoud HR, Powley TL. Interaction between parasympathetic and sympathetic nerves in prevertebral ganglia: morphological evidence for vagal efferent innervation of ganglion cells in the rat. Microsc Res Tech 1996 35 : 80 6. (Pubitemid 26282078)
22. Bellinger DL, Lorton D, Hamill RW, Felten SY, Felten DL. Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergic innervation. Brain Behav Immun 1993 7 : 191 204. (Pubitemid 23302158)
23. 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 13.
24. Bellinger DL, Felten SY, Lorton D, Felten DL. Origin of noradrenergic innervation of the spleen in rats. Brain Behav Immun 1989 3 : 291 311.
25. Nance DM, Burns J. Innervation of the spleen in the rat: evidence for absence of afferent innervation. Brain Behav Immun 1989 3 : 281 90.
26. Cano G, Sved AF, Rinaman L, Rabin BS, Card JP. Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing. J Comp Neurol 2001 439 : 1 18. (Pubitemid 32847017)
27. Klein RL, Wilson SP, Dzielak DJ, Yang WH, Viveros OH. Opioid peptides and noradrenaline co-exist in large dense-cored vesicles from sympathetic nerve. Neuroscience 1982 7 : 2255 61. (Pubitemid 12034588)
28. Felten DL, Ackerman KD, Wiegand SJ, Felten SY. Noradrenergic sympathetic innervation of the spleen: I. Nerve fibers associate with lymphocytes and macrophages in specific compartments of the splenic white pulp. J Neurosci Res 1987 18 : 28 36. (Pubitemid 18101344)
29. Kees MG, Pongratz G, Kees F, Scholmerich J, Straub RH. Via beta-adrenoceptors, stimulation of extrasplenic sympathetic nerve fibers inhibits lipopolysaccharide-induced TNF secretion in perfused rat spleen. J Neuroimmunol 2003 145 : 77 85. (Pubitemid 37492878)
30. Spengler RN, Allen RM, Remick DG, Strieter RM, Kunkel SL. Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor. J Immunol 1990 145 : 1430 4. (Pubitemid 20255049)
31. Deng J, Muthu K, Gamelli R, Shankar R, Jones SB. Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis. Am J Physiol Cell Physiol 2004 287 : C730 6. (Pubitemid 39095860)
32. Lips KS, Konig P, Schatzle K et al. Coexpression and spatial association of nicotinic acetylcholine receptor subunits alpha7 and alpha10 in rat sympathetic neurons. J Mol Neurosci 2006 30 : 15 6. (Pubitemid 46035300)
33. Skok MV, Voitenko LP, Voitenko SV et al. Alpha subunit composition of nicotinic acetylcholine receptors in the rat autonomic ganglia neurons as determined with subunit-specific anti-alpha(181-192) peptide antibodies. Neuroscience 1999 93 : 1427 36. (Pubitemid 29397572)
34. Franceschini D, Orr-Urtreger A, Yu W et al. Altered baroreflex responses in alpha7 deficient mice. Behav Brain Res 2000 113 : 3 10. (Pubitemid 30645538)
35. Brandon KW, Rand MJ. Acetylcholine and the sympathetic innervation of the spleen. J Physiol 1961 157 : 18 32.
36. Bulloch K, Damavandy T, Badamchian M. Characterization of choline O-acetyltransferase (ChAT) in the BALB-C mouse spleen. Int J Neurosci 1994 76 : 141 9. (Pubitemid 2098746)
37. Rinner I, Kawashima K, Schauenstein K. Rat lymphocytes produce and secrete acetylcholine in dependence of differentiation and activation. J Neuroimmunol 1998 81 : 31 7. (Pubitemid 28248181)
38. Okamoto S, Ibaraki K, Hayashi S, Saito M. Ventromedial hypothalamus suppresses splenic lymphocyte activity through sympathetic innervation. Brain Res 1996 739 : 308 13. (Pubitemid 26387390)
39. Ganta CK, Lu N, Helwig BG et al. Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Am J Physiol Heart Circ Physiol 2005 289 : H1683 91. (Pubitemid 41369013)
40. Katafuchi T, Take S, Hori T. Roles of sympathetic nervous system in the suppression of cytotoxicity of splenic natural killer cells in the rat. J Physiol 1993 465 : 343 57. (Pubitemid 23201400)
41. van Westerloo DJ, Giebelen IA, Florquin S et al. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis 2005 191 : 2138 48. (Pubitemid 40800586)
42. Kessler W, Traeger T, Westerholt A et al. The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis. Langenbecks Arch Surg 2006 391 : 83 7.
43. Song XM, Li JG, Wang YL et al. The protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats. Shock 2008 30 : 468 72.
44. van Westerloo DJ, Giebelen IA, Meijers JC et al. Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis during endotoxemia in rats. J Thromb Haemost 2006 4 : 1997 2002. (Pubitemid 44226780)
45. Wang H, Liao H, Ochani M et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 2004 10 : 1216 21. (Pubitemid 39540438)
46. 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 44. (Pubitemid 46598966)
47. Giebelen IA, van Westerloo DJ, Larosa GJ, de Vos AF, van der PT. Stimulation of alpha 7 cholinergic receptors inhibits lipopolysaccharide-induced neutrophil recruitment by a tumor necrosis factor alpha-independent mechanism. Shock 2007 27 : 443 7. (Pubitemid 46594978)
48. Rakonczay Z Jr., Hegyi P, Takacs T, McCarroll J, Saluja AK. The role of NF-kappaB activation in the pathogenesis of acute pancreatitis. Gut 2008 57 : 259 67.
49. van Westerloo DJ, Giebelen IA, Florquin S et al. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. Gastroenterology 2006 130 : 1822 30.
50. Zingarelli B, Squadrito F, Altavilla D, Calapai G, Di Rosa M, Caputi AP. Role of tumor necrosis factor-alpha in acute hypovolemic hemorrhagic shock in rats. Am J Physiol 1994 266 : H1512 5. (Pubitemid 2084504)
51. Squadrito F, Altavilla D, Canale P et al. Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock. Br J Pharmacol 1994 113 : 1153 8. (Pubitemid 24364392)
52. Squadrito F, Altavilla D, Canale P et al. Contribution of intercellular adhesion molecule 1 (ICAM-1) to the pathogenesis of splanchnic artery occlusion shock in the rat. Br J Pharmacol 1994 113 : 912 6. (Pubitemid 24326833)
53. Guarini S, Altavilla D, Cainazzo MM et al. Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock. Circulation 2003 107 : 1189 94. (Pubitemid 36297213)
54. Altavilla D, Guarini S, Bitto A et al. Activation of the cholinergic anti-inflammatory pathway reduces NF-kappab activation, blunts TNF-alpha production, and protects againts splanchic artery occlusion shock. Shock 2006 25 : 500 6. (Pubitemid 43755921)
55. Bernik TR, Friedman SG, Ochani M et al. Cholinergic antiinflammatory pathway inhibition of tumor necrosis factor during ischemia reperfusion. J Vasc Surg 2002 36 : 1231 6. (Pubitemid 36236348)
56. Guarini S, Cainazzo MM, Giuliani D et al. Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway. Cardiovasc Res 2004 63 : 357 65. (Pubitemid 38900850)
57. Luyer MD, Greve JW, Hadfoune M, Jacobs JA, Dejong CH, Buurman WA. Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med 2005 202 : 1023 9. (Pubitemid 41464495)
58. Yeboah MM, Xue X, Duan B et al. Cholinergic agonists attenuate renal ischemia-reperfusion injury in rats. Kidney Int 2008 74 : 62 9.
59. Sadis C, Teske G, Stokman G et al. Nicotine protects kidney from renal ischemia-reperfusion injury through the cholinergic anti-inflammatory pathway. PLoS ONE 2007 2 : e469.
60. Kalff JC, Schraut WH, Simmons RL, Bauer AJ. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg 1998 228 : 652 63. (Pubitemid 128719595)
61. 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 2005 6 : 844 51. (Pubitemid 43090471)
62. The FO, Boeckxstaens GE, Snoek SA et al. Activation of the cholinergic anti-inflammatory pathway ameliorates postoperative ileus in mice. Gastroenterology 2007 133 : 1219 28. (Pubitemid 47494458)
63. 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 23. (Pubitemid 40524679)
64. Millar NS. Assembly and subunit diversity of nicotinic acetylcholine receptors. Biochem Soc Trans 2003 31 : 869 74. (Pubitemid 36981146)
65. Berg DK, Conroy WG. Nicotinic alpha 7 receptors: synaptic options and downstream signaling in neurons. J Neurobiol 2002 53 : 512 23. (Pubitemid 35375582)
66. Drisdel RC, Green WN. Neuronal alpha-bungarotoxin receptors are alpha7 subunit homomers. J Neurosci 2000 20 : 133 9. (Pubitemid 30220499)
67. Charpantier E, Wiesner A, Huh KH et al. Alpha7 neuronal nicotinic acetylcholine receptors are negatively regulated by tyrosine phosphorylation and Src-family kinases. J Neurosci 2005 25 : 9836 49. (Pubitemid 41528021)
68. Dajas-Bailador FA, Soliakov L, Wonnacott S. Nicotine activates the extracellular signal-regulated kinase 1-2 via the alpha7 nicotinic acetylcholine receptor and protein kinase A, in SH-SY5Y cells and hippocampal neurones. J Neurochem 2002 80 : 520 30. (Pubitemid 36383035)
69. Kihara T, Shimohama S, Sawada H et al. Alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. J Biol Chem 2001 276 : 13541 6. (Pubitemid 37391721)
70. 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 74.
71. Takeda K, Akira S. TLR signaling pathways. Semin Immunol 2004 16 : 3 9. (Pubitemid 38147427)
72. Cheong R, Hoffmann A, Levchenko A. Understanding NF-kappaB signaling via mathematical modeling. Mol Syst Biol 2008 4 : 192.
73. 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 2006 146 : 116 23. (Pubitemid 44393846)
74. O'Shea JJ, Murray PJ. Cytokine signaling modules in inflammatory responses. Immunity 2008 28 : 477 87.
75. Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol 2007 178 : 2623 9. (Pubitemid 46333135)
76. 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 91. (Pubitemid 40862796)
77. Yoshida Y, Kumar A, Koyama Y et al. Interleukin 1 activates STAT3-nuclear factor-kappaB cross-talk via a unique T. J Biol Chem 2004 279 : 1768 76.
78. de Jonge WJ, Ulloa L. The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 2007 151 : 915 29. (Pubitemid 47195518)
79. Broide RS, Leslie FM. The alpha7 nicotinic acetylcholine receptor in neuronal plasticity. Mol Neurobiol 1999 20 : 1 16.
80. Razani-Boroujerdi S, Boyd RT, Davila-Garcia MI et al. T cells express alpha7-nicotinic acetylcholine receptor subunits that require a functional TCR and leukocyte-specific protein tyrosine kinase for nicotine-induced Ca2+ response. J Immunol 2007 179 : 2889 98.
81. Kawashima K, Fujii T, Watanabe Y, Misawa H. Acetylcholine synthesis and muscarinic receptor subtype mRNA expression in T-lymphocytes. Life Sci 1998 62 : 1701 5. (Pubitemid 28210265)
82. Kawashima K, Yoshikawa K, Fujii YX, Moriwaki Y, Misawa H. Expression and function of genes encoding cholinergic components in murine immune cells. Life Sci 2007 80 : 2314 9. (Pubitemid 46818285)
83. Neumann S, Razen M, Habermehl P et al. The non-neuronal cholinergic system in peripheral blood cells: effects of nicotinic and muscarinic receptor antagonists on phagocytosis, respiratory burst and migration. Life Sci 2007 80 : 2361 4. (Pubitemid 46818263)
84. Grando SA, Kist DA, Qi M, Dahl MV. Human keratinocytes synthesize, secrete, and degrade acetylcholine. J Invest Dermatol 1993 101 : 32 6. (Pubitemid 23213008)
85. Kawashima K, Watanabe N, Oohata H et al. Synthesis and release of acetylcholine by cultured bovine arterial endothelial cells. Neurosci Lett 1990 119 : 156 8. (Pubitemid 20379245)
86. Wessler I, Herschel S, Bittinger F, Kirkpatrick CJ. Release of non-neuronal acetylcholine from the isolated human placenta is affected by antidepressants. Life Sci 2007 80 : 2210 3. (Pubitemid 46818259)
87. Yoshida M, Inadome A, Maeda Y et al. Non-neuronal cholinergic system in human bladder urothelium. Urology 2006 67 : 425 30. (Pubitemid 43189886)
88. Wessler IK, Kirkpatrick CJ. The Non-neuronal cholinergic system: an emerging drug target in the airways. Pulm Pharmacol Ther 2001 14 : 423 34. (Pubitemid 34081694)
89. Kawashima K, Fujii T. Basic and clinical aspects of non-neuronal acetylcholine: overview of non-neuronal cholinergic systems and their biological significance. J Pharmacol Sci 2008 106 : 167 73.
90. Wessler I, Kilbinger H, Bittinger F, Unger R, Kirkpatrick CJ. The non-neuronal cholinergic system in humans: expression, function and pathophysiology. Life Sci 2003 72 : 2055 61. (Pubitemid 36298947)
91. Kwon JY, Kim YH, Kim SH et al. Difference in the expression of alpha 7 nicotinic receptors in the placenta in normal versus severe preeclampsia pregnancies. Eur J Obstet Gynecol Reprod Biol 2007 132 : 35 9.
92. Lips KS, Bruggmann D, Pfeil U, Vollerthun R, Grando SA, Kummer W. Nicotinic acetylcholine receptors in rat and human placenta. Placenta 2005 26 : 735 46. (Pubitemid 41535479)
93. Dowling O, Rochelson B, Way K, Al Abed Y, Metz CN. Nicotine inhibits cytokine production by placenta cells via NFkappaB: potential role in pregnancy-induced hypertension. Mol Med 2007 13 : 576 83. (Pubitemid 350228718)
94. Rusterholz C, Hahn S, Holzgreve W. Role of placentally produced inflammatory and regulatory cytokines in pregnancy and the etiology of preeclampsia. Semin Immunopathol 2007 29 : 151 62. (Pubitemid 47596394)
95. Gilbert JS, Ryan MJ, LaMarca BB, Sedeek M, Murphy SR, Granger JP. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol 2008 294 : H541 50.
96. Fujii T, Yamada S, Yamaguchi N, Fujimoto K, Suzuki T, Kawashima K. Species differences in the concentration of acetylcholine, a neurotransmitter, in whole blood and plasma. Neurosci Lett 1995 201 : 207 10. (Pubitemid 26013099)
97. Kawashima K, Oohata H, Fujimoto K, Suzuki T. Plasma concentration of acetylcholine in young women. Neurosci Lett 1987 80 : 339 42. (Pubitemid 17140138)
98. Kawashima K, Fujii T. Extraneuronal cholinergic system in lymphocytes. Pharmacol Ther 2000 86 : 29 48. (Pubitemid 30173143)
99. Kawashima K, Oohata H, Fujimoto K, Suzuki T. Extraneuronal localization of acetylcholine and its release upon nicotinic stimulation in rabbits. Neurosci Lett 1989 104 : 336 9. (Pubitemid 19231156)
100. Yamada S, Fujii T, Kawashima K. Oral administration of KW-5092, a novel gastroprokinetic agent with acetylcholinesterase inhibitory and acetylcholine release enhancing activities, causes a dose-dependent increase in the blood acetylcholine content of beagle dogs. Neurosci Lett 1997 225 : 25 8. (Pubitemid 27154209)
101. Hofer S, Eisenbach C, Lukic IK et al. Pharmacologic cholinesterase inhibition improves survival in experimental sepsis. Crit Care Med 2008 36 : 404 8.
102. Pollak Y, Gilboa A, Ben Menachem O, Ben Hur T, Soreq H, Yirmiya R. Acetylcholinesterase inhibitors reduce brain and blood interleukin-1beta production. Ann Neurol 2005 57 : 741 5. (Pubitemid 40628864)
103. Ofek K, Krabbe KS, Evron T et al. Cholinergic status modulations in human volunteers under acute inflammation. J Mol Med 2007 85 : 1239 51. (Pubitemid 47622221)
104. Pullan RD, Rhodes J, Ganesh S et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med 1994 330 : 811 5. (Pubitemid 24083559)
105. Oommen J, Morrell M, Fisher RS. Experimental electrical stimulation therapy for epilepsy. Curr Treat Options Neurol 2005 7 : 261 71. (Pubitemid 41015270)
106. Tecoma ES, Iragui VJ. Vagus nerve stimulation use and effect in epilepsy: what have we learned? Epilepsy Behav 2006 8 : 127 36. (Pubitemid 43103840)
107. Walsh SP, Kling MA. VNS and depression: current status and future directions. Expert Rev Med Devices 2004 1 : 155 60. (Pubitemid 40220426)
108. Ghia JE, Blennerhassett P, Kumar-Ondiveeran H, Verdu EF, Collins SM. The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology 2006 131 : 1122 30. (Pubitemid 44498700)
109. Ghia JE, Blennerhassett P, Collins SM. Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression. J Clin Invest 2008 118 : 2209 18.
110. 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 2008 23 : 41 5.
111. Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, van den BH. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. BMJ 2005 331 : 321 7. (Pubitemid 41113141)
112. Alkondon M, Pereira EF, Cortes WS, Maelicke A, Albuquerque EX. Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons. Eur J Neurosci 1997 9 : 2734 42. (Pubitemid 28082962)
113. Papke RL, Bencherif M, Lippiello P. An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the alpha 7 subtype. Neurosci Lett 1996 213 : 201 4. (Pubitemid 26264379)
114. Rivera CA, Wheeler MD, Enomoto N, Thurman RG. A choline-rich diet improves survival in a rat model of endotoxin shock. Am J Physiol 1998 275 : G862 7. (Pubitemid 28491844)
115. Ilcol YO, Yilmaz Z, Ulus IH. Endotoxin alters serum-free choline and phospholipid-bound choline concentrations, and choline administration attenuates endotoxin-induced organ injury in dogs. Shock 2005 24 : 288 93. (Pubitemid 41279495)
116. Detopoulou P, Panagiotakos DB, Antonopoulou S, Pitsavos C, Stefanadis C. Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. Am J Clin Nutr 2008 87 : 424 30.
117. Antonica A, Magni F, Mearini L, Paolocci N. Vagal control of lymphocyte release from rat thymus. J Auton Nerv Syst 1994 48 : 187 97. (Pubitemid 24210344)
118. Antonica A, Ayroldi E, Magni F, Paolocci N. Lymphocyte traffic changes induced by monolateral vagal denervation in mouse thymus and peripheral lymphoid organs. J Neuroimmunol 1996 64 : 115 22. (Pubitemid 26094629)
119. Lehrer P, Vaschillo E, Lu SE et al. Heart rate variability biofeedback: effects of age on heart rate variability, baroreflex gain, and asthma. Chest 2006 129 : 278 84. (Pubitemid 43289845)
120. Nakao M, Yano E, Nomura S, Kuboki T. Blood pressure-lowering effects of biofeedback treatment in hypertension: a meta-analysis of randomized controlled trials. Hypertens Res 2003 26 : 37 46. (Pubitemid 36193097)
121. Kaushik R, Kaushik RM, Mahajan SK, Rajesh V. Biofeedback assisted diaphragmatic breathing and systematic relaxation versus propranolol in long term prophylaxis of migraine. Complement Ther Med 2005 13 : 165 74. (Pubitemid 41258545)
122. Bernik TR, Friedman SG, Ochani M et al. Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 2002 195 : 781 8. (Pubitemid 34259722)
123. Wittebole X, Hahm S, Coyle SM, Kumar A, Calvano SE, Lowry SF. Nicotine exposure alters in vivo human responses to endotoxin. Clin Exp Immunol 2007 147 : 28 34.
124. Mioni C, Bazzani C, Giuliani D et al. Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia-reperfusion injury in rats. Crit Care Med 2005 33 : 2621 8. (Pubitemid 41682117)