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Reflex control of immunity
Open accessAbstract
Inflammation can cause damage and even death. What controls this primitive and potentially lethal innate immune response to injury and infection? Molecular and neurophysiological studies during the past decade have revealed a pivotal answer: immunity is coordinated by neural circuits that operate reflexively. The afferent arc of the reflex consists of nerves that sense injury and infection. This activates efferent neural circuits, including the cholinergic anti-inflammatory pathway, that modulate immune responses and the progression of inflammatory diseases. It might be possible to develop therapeutics that target neural networks for the treatment of inflammatory disorders.
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“Interestingly, evidence suggests that activation of the parasympathetic nervous system also can modulate the activity of the immune system via alterations in vagal release of acetylcholine from T cells (Tracey, 2009).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Tracey, 2009
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“Additional evidence suggests that the parasympathetic nervous system modulates immune responses at a regional level through both the efferent and afferent fibers of the vagus nerve, enabling it to prevent excessive inflammation”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Tracey, 2009
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“For example, motor vagus nerve stimulation attenuates the activation of NFκB following an immune challenge (Tracey, 2009).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Tracey, 2009
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“ACh binds to α-7-nicotinic ACh receptors of those macrophages to inhibit the TNF-α (69).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [69]
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“with evidence that vagal activity can modulate immune responses at a regional level through both the efferent and afferent fibers of the vagus nerve, to prevent excessive inflammation”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Tracey, 2009
In the citing paper
“Multiple non-exclusive pathways participate in the activation of the HPA axis upon cerebral or peripheral immune challenges. When an immunogenic insult takes place in the brain, various inflammatory mediators produced locally may trigger the HPA axis.”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [21]
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Citations
Cites
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618 · cited 1×
“1 ) — that interact with Toll-like receptors (TLRs), which transduce intracellular signals, ultimately leading to the activation of NF-κB and the increased release of pro-inflammatory cytokine”
BackgroundVagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., Wang, H., Abumrad, N., Eaton, J. W., & Tracey, K. J. (2000) · Nature · doi:10.1038/35013070 · Cited by 4,211 · cited 1×
“The 'inflammatory reflex' is one example of how action potentials originating in neurons continuously shape immunit”
BackgroundSelf-citationTracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728 · cited 1×
“The 'inflammatory reflex' is one example of how action potentials originating in neurons continuously shape immunit”
BackgroundSelf-citationNicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., et al. (2003) · Nature · doi:10.1038/nature01339 · Cited by 3,228
Self-citationDAMPs, PAMPs and alarmins: all we need to know about danger
Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738 · cited 1×
“These molecules can activate TLRs, mannose receptors and nucleotide-binding oligomerization domain (NOD)-like receptors”
BackgroundThe immune response in atherosclerosis: a double-edged sword
Hansson, G. K., & Libby, P. (2006) · Nature reviews. Immunology · doi:10.1038/nri1882 · Cited by 2,220
Mammalian nicotinic acetylcholine receptors: from structure to function
Albuquerque, E. X., Pereira, E. F. R., Alkondon, M., & Rogers, S. W. (2009) · Physiological Reviews · doi:10.1152/physrev.00015.2008 · Cited by 1,724 · cited 1×
“Acetylcholine, the principal parasympathetic neurotransmitter, interacts with the G protein-coupled muscarinic acetylcholine receptors M1–M5 and nicotinic ligand-gated ion channels (termed neuronal type I–III and muscle type IV”
BackgroundPhysiology and immunology of the cholinergic antiinflammatory pathway
Tracey, K. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30555 · Cited by 1,563
Self-citationTumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1.
Dinarello, C. A., Cannon, J. G., Wolff, S. M., Bernheim, H. A., Beutler, B., Cerami, A., Figari, I. S., Palladino, M. A., & O'Connor, J. V. (1986) · The Journal of experimental medicine · doi:10.1084/jem.163.6.1433 · Cited by 1,472
Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis
Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E. J., et al. (2004) · Nature Medicine · doi:10.1038/nm1124 · Cited by 1,170
Self-citationde Jonge, W. J., van der Zanden, E. P., The, F. O., Bijlsma, M. F., van Westerloo, D. J., Bennink, R. J., Berthoud, H.-R., Uematsu, S., Akira, S., van den Wijngaard, R. M., et al. (2005) · Nature Immunology · doi:10.1038/ni1229 · Cited by 1,074
Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens
Sternberg, E. M. (2006) · Nature Reviews Immunology · doi:10.1038/nri1810 · Cited by 1,064
The role of vagal function in the risk for cardiovascular disease and mortality
Thayer, J. F., & Lane, R. D. (2007) · Biological Psychology · doi:10.1016/j.biopsycho.2005.11.013 · Cited by 1,033 · cited 1×
“What is known about the activity of inflammatory diseases in humans with decreased vagus nerve activity, and can determining the basal levels of vagus nerve activity act as a surrogate marker for measuring the activity of the inflammatory reflex in resting conditions? A complete discussion of the clinical studies addr…”
BackgroundSplenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia
Rosas‐Ballina, M., Ochani, M., Parrish, W. R., Ochani, K., Harris, Y., Huston, J. M., Chavan, S. S., & Tracey, K. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803237105 · Cited by 762
Self-citationBeyond Heart Rate Variability: Vagal Regulation of Allostatic Systems
THAYER, J. F., & STERNBERG, E. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1366.014 · Cited by 703
Huston, J. M., Ochani, M., Rosas-Ballina, M., Liao, H., Ochani, K., Pavlov, V. A., Gallowitsch-Puerta, M., Ashok, M., Czura, C. J., Foxwell, B., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052362 · Cited by 683 · cited 1×
“Direct electrical stimulation of the cholinergic anti-inflammatory pathway with electrodes that generate action potentials in the vagus nerve significantly inhibits cytokine production by innate immune cells in the spleen, liver, gastrointestinal tract, heart and other tissues that are innervated by the vagus nerv”
BackgroundSelf-citationMuscarinic acetylcholine receptors: mutant mice provide new insights for drug development
Wess, J., Eglen, R. M., & Gautam, D. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2379 · Cited by 637
Elaborate interactions between the immune and nervous systems
Steinman, L. (2004) · Nature Immunology · doi:10.1038/ni1078 · Cited by 556
Cholinergic modulation of microglial activation by α7 nicotinic receptors
Shytle, R. D., Mori, T., Townsend, K. P., Vendrame, M., Sun, N., Zeng, J., Ehrhart, J. C., Silver, A. A., Sanberg, P. R., & Tan, J. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2004.02347.x · Cited by 537
Pharmacological stimulation of the cholinergic antiinflammatory pathway
Bernik, T. R., Friedman, S. G., Ochani, M., DiRaimo, R., Ulloa, L., Yang, H., Sudan, S., Czura, C. J., Ivanova, S. M., & Tracey, K. J. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011714 · Cited by 529 · cited 1×
“Direct electrical stimulation of the cholinergic anti-inflammatory pathway with electrodes that generate action potentials in the vagus nerve significantly inhibits cytokine production by innate immune cells in the spleen, liver, gastrointestinal tract, heart and other tissues that are innervated by the vagus nerv”
BackgroundSelf-citationWatkins, L. R., Goehler, L. E., Relton, J. K., Tartaglia, N., Silbert, L., Martin, D., & Maier, S. F. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(94)11105-r · Cited by 516
Saeed, R. W., Varma, S., Peng-Nemeroff, T., Sherry, B., Balakhaneh, D., Huston, J., Tracey, K. J., Al-Abed, Y., & Metz, C. N. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040463 · Cited by 489 · cited 1×
“Direct electrical stimulation of the cholinergic anti-inflammatory pathway with electrodes that generate action potentials in the vagus nerve significantly inhibits cytokine production by innate immune cells in the spleen, liver, gastrointestinal tract, heart and other tissues that are innervated by the vagus nerv”
BackgroundSelf-citationProspective Long‐Term Study of Vagus Nerve Stimulation for the Treatment of Refractory Seizures
DeGiorgio, C. M., Schachter, S. C., Handforth, A., Salinsky, M., Thompson, J., Uthman, B., Reed, R., Collin, S., Tecoma, E., Morris, G. L., et al. (2000) · Epilepsia · doi:10.1111/j.1528-1157.2000.tb00325.x · Cited by 479
Pavlov, V. A., Parrish, W. R., Rosas‐Ballina, M., Ochani, M., Gallowitsch‐Puerta, M., Ochani, K., Chavan, S. S., Al‐Abed, Y., & Tracey, K. J. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.06.011 · Cited by 437 · cited 1×
“The administration of intracerebral McN-A 343, a selective muscarinic acetylcholine receptor M1 receptor agonist, significantly increases the firing rate of action potentials in the vagus nerve and inhibits innate immune responses in the peripher”
BackgroundSelf-citationKihara, T., Shimohama, S., Sawada, H., Honda, K., Nakamizo, T., Shibasaki, H., Kume, T., & Akaike, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008035200 · Cited by 412
Ghia, J., Blennerhassett, P. A., Kumar–Ondiveeran, H., Verdu, E. F., & Collins, S. M. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.08.016 · Cited by 412
The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice
van Westerloo, D. J., Giebelen, I. A., Florquin, S., Bruno, M. J., LaRosa, G. J., Ulloa, L., Tracey, K. J., & van der Poll, T. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.02.022 · Cited by 377
Self-citationImmune regulation of central nervous system functions: from sickness responses to pathological pain
Watkins, L. R., & Maier, S. F. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01443.x · Cited by 367
Exercise training modulates cytokines activity in coronary heart disease patients
Goldhammer, E., Tanchilevitch, A., Maor, I., Beniamini, Y., Rosenschein, U., & Sagiv, M. (2005) · International Journal of Cardiology · doi:10.1016/j.ijcard.2004.08.073 · Cited by 363
Pavlov, V. A., Ochani, M., Yang, L., Gallowitsch‐Puerta, M., Ochani, K., Lin, X., Levi, J., Parrish, W. R., Rosas‐Ballina, M., Czura, C. J., et al. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000259381.56526.96 · Cited by 357
Self-citationGoehler, L. E., Gaykema, R. P. A., Nguyen, K. T., Lee, J. E., Tilders, F. J. H., Maier, S. F., & Watkins, L. R. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02799.1999 · Cited by 357
Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia
Pavlov, V. A., Ochani, M., Gallowitsch-Puerta, M., Ochani, K., Huston, J. M., Czura, C. J., Al-Abed, Y., & Tracey, K. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600506103 · Cited by 336
Self-citationParrish, W. R., Rosas‐Ballina, M., Gallowitsch‐Puerta, M., Ochani, M., Ochani, K., Yang, L., Hudson, L., Lin, X., Patel, N. B., Johnson, S. M., et al. (2008) · Molecular Medicine · doi:10.2119/2008-00079.parrish · Cited by 335
Self-citationThe lymphocytic cholinergic system and its contribution to the regulation of immune activity
Kawashima, K., & Fujii, T. (2003) · Life Sciences · doi:10.1016/j.lfs.2003.09.037 · Cited by 327 · cited 1×
“Potential candidates include endothelial cells and lymphocytes such as splenic T cells, which are richly innervated by the catecholaminergic axons travelling in the splenic nerv”
BackgroundGoehler, L. E., Relton, J. K., Dripps, D. J., Kiechle, R., Tartaglia, N. R., Maier, S. F., & Watkins, L. R. (1997) · Brain Research Bulletin · doi:10.1016/s0361-9230(97)00020-8 · Cited by 326
The Cholinergic Anti‐Inflammatory Pathway Regulates the Host Response during Septic Peritonitis
van Westerloo, D. J., Giebelen, I. A. J., Florquin, S., Daalhuisen, J., Bruno, M. J., de Vos, A. F., Tracey, K. J., & van der Poll, T. (2005) · The Journal of Infectious Diseases · doi:10.1086/430323 · Cited by 316
Self-citationGuarini, S., Altavilla, D., Cainazzo, M.-M., Giuliani, D., Bigiani, A., Marini, H., Squadrito, G., Minutoli, L., Bertolini, A., Marini, R., et al. (2003) · Circulation · doi:10.1161/01.cir.0000050627.90734.ed · Cited by 315
Huston, J. M., Gallowitsch‐Puerta, M., Ochani, M., Ochani, K., Yuan, R., Rosas‐Ballina, M., Ashok, M., Goldstein, R. S., Chavan, S. S., Pavlov, V. A., et al. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000288102.15975.ba · Cited by 307
Self-citationYoshikawa, H., Kurokawa, M. S., Ozaki, N., Nara, K., Atou, K., Takada, E., Kamochi, H., & Suzuki, N. (2006) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2006.03169.x · Cited by 295
The relationship between heart rate variability and inflammatory markers in cardiovascular diseases
Haensel, A., Mills, P. J., Nelesen, R. A., Ziegler, M. G., & Dimsdale, J. E. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.08.007 · Cited by 291
Stimulation of nicotinic acetylcholine receptors attenuates collagen‐induced arthritis in mice
van Maanen, M. A., Lebre, M. C., van der Poll, T., LaRosa, G. J., Elbaum, D., Vervoordeldonk, M. J., & Tak, P. P. (2008) · Arthritis & Rheumatism · doi:10.1002/art.24177 · Cited by 276
Norepinephrine, the β-Adrenergic Receptor, and Immunity
Sanders, V. M., & Straub, R. H. (2002) · Brain, Behavior, and Immunity · doi:10.1006/brbi.2001.0639 · Cited by 272
Spengler, R. N., Chensue, S. W., Giacherio, D. A., Blenk, N., & Kunkel, S. L. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.6.3024 · Cited by 269
RR Interval Variability Is Inversely Related to Inflammatory Markers: The CARDIA Study
Sloan, R. P., McCreath, H., Tracey, K. J., Sidney, S., Liu, K., & Seeman, T. (2007) · Molecular Medicine · doi:10.2119/2006-00112.sloan · Cited by 264
Self-citationKawashima, K. (2004) · Frontiers in bioscience · doi:10.2741/1390 · Cited by 262
Niijima, A. (1996) · Journal of the Autonomic Nervous System · doi:10.1016/s0165-1838(96)00098-7 · Cited by 261 · cited 1×
“Together with evidence that afferent vagus nerve firing rates increase following the administration of IL-1 (Ref”
BackgroundSympathetic modulation of immunity: Relevance to disease
Bellinger, D. L., Millar, B. A., Perez, S. D., Carter, J., Wood, C. A., ThyagaRajan, S., Molinaro, C. A., Lubahn, C. L., & Lorton, D. (2008) · Cellular Immunology · doi:10.1016/j.cellimm.2007.09.005 · Cited by 256
NF-κB in the Survival and Plasticity of Neurons
Mattson, M. P. (2005) · Neurochemical Research · doi:10.1007/s11064-005-6961-x · Cited by 254 · cited 1×
“NF-κB activation in neurons has been implicated in controlling the transcription of genes, the products of which are involved in inflammation, injury and ischaemia and processes underlying memory formation and neuronal plasticit”
Suzuki, T., Hide, I., Matsubara, A., Hama, C., Harada, K., Miyano, K., Andrä, M., Matsubayashi, H., Sakai, N., Kohsaka, S., et al. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20850 · Cited by 247 · cited 1×
“In microglial cells, α7nAChR signalling inhibits endotoxin-induced TNF release by a mechanism that involves decreased phosphorylation of the MAPKs p38 (also known as MAPK14) and p44 (also known as MAPK3”
BackgroundRegulation of muscarinic acetylcholine receptor signaling
van Koppen, C. J., & Kaiser, B. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(03)00032-9 · Cited by 239 · cited 1×
“Acetylcholine, the principal parasympathetic neurotransmitter, interacts with the G protein-coupled muscarinic acetylcholine receptors M1–M5 and nicotinic ligand-gated ion channels (termed neuronal type I–III and muscle type IV”
BackgroundGhia, J.-E., Blennerhassett, P., & Collins, S. M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32849 · Cited by 233
Tracey, K. J., Morgello, S., Koplin, B., Fahey, T. J., Fox, J., Aledo, A., Manogue, K. R., & Cerami, A. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114937 · Cited by 230 · cited 1×
“Early investigators studying the host response to infection and injury determined that brain neurons express specific receptors that respond to intracerebral cytokines to mediate physiological and behavioural change”
BackgroundSelf-citationOxygen-sensing neurons in the central nervous system
Neubauer, J. A., & Sunderram, J. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00831.2003 · Cited by 215
Yu, B., Becnel, J., Zerfaoui, M., Rohatgi, R., Boulares, A. H., & Nichols, C. D. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.143461 · Cited by 211 · cited 1×
“By contrast, activation of 5-hydroxytryptamine receptors or β-adrenergic receptors inhibits pro-inflammatory cytokine release and suppresses inflammatio”
BackgroundLONG‐TERM REGULATION OF ARTERIAL BLOOD PRESSURE BY HYPOTHALAMIC NUCLEI: SOME CRITICAL QUESTIONS
Dampney, R., Horiuchi, J., Killinger, S., Sheriff, M., Tan, P. S. P., & McDowall, L. M. (2005) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2005.04205.x · Cited by 196
Dajas‐Bailador, F., Soliakov, L. S., & Wonnacott, S. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00725.x · Cited by 196 · cited 1×
“Increases in intracellular calcium mediated by α7nAChR signalling induce protein kinase A-dependent activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2 (Ref”
BackgroundHeart rate variability as early marker of multiple organ dysfunction syndrome in septic patients
Pontet, J., Contreras, P., Curbelo, A., Medina, J., Noveri, S., Bentancourt, S., & Migliaro, E. R. (2003) · Journal of Critical Care · doi:10.1016/j.jcrc.2003.08.005 · Cited by 195
Razani‐Boroujerdi, S., Boyd, R. T., Dávila‐García, M. I., Nandi, J. S., Mishra, N. C., Singh, S. P., Peña-Philippides, J. C., Langley, R. J., & Sopori, M. L. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.5.2889 · Cited by 174
Heart rate variability after acute traumatic brain injury in children
Biswas, A. K., Scott, W. A., Sommerauer, J. F., & Luckett, P. M. (2000) · Critical Care Medicine · doi:10.1097/00003246-200012000-00030 · Cited by 173
Characterization of vagal innervation to the rat celiac, suprarenal and mesenteric ganglia
Berthoud, H., & Powley, T. L. (1993) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(93)90046-w · Cited by 173
The contribution of the vagus nerve in interleukin-1β-induced fever is dependent on dose
Hansen, M. K., O'Connor, K. A., Goehler, L. E., Watkins, L. R., & Maier, S. F. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.4.r929 · Cited by 169
Heart Rate Variability in Emergency Department Patients with Sepsis
Barnaby, D., Ferrick, K., Kaplan, D. T., Shah, S., Bijur, P., & Gallagher, E. J. (2002) · Academic Emergency Medicine · doi:10.1197/aemj.9.7.661 · Cited by 167
Heart Rate Variability in Emergency Department Patients with Sepsis
Barnaby, D. P., Ferrick, K. J., Kaplan, D. T., Shah, S. P., Bijur, P. E., & Gallagher, E. J. (2002) · Academic Emergency Medicine · doi:10.1111/j.1553-2712.2002.tb02143.x · Cited by 162
Heart rate variability in patients with rheumatoid arthritis
Evrengül, H., Dursunoglu, D., Cobankara, V., Polat, B., Seleci, D., Kabukçu, S., Kaftan, A., Semiz, E., & Kilic, M. (2004) · Rheumatology International · doi:10.1007/s00296-003-0357-5 · Cited by 159
Autonomic Vagal Nerve Dysfunction in Patients with Ulcerative Colitis
Lindgren, S. C., Stewénius, J., Sjölund, K., Lilja, B., & Sundkvist, G. (1993) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365529309096103 · Cited by 154
Conceptual development of the immune system as a sixth sense
Blalock, J. E., & Smith, E. M. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.09.004 · Cited by 153 · cited 1×
“Another large body of work had established that neurotransmitters can interact with immune cells and alter their functio”
Charpantier, E., Wiesner, A., Huh, K.-H., Ogier, R., Hoda, J., Allaman, G., Raggenbass, M., Feuerbach, D., Bertrand, D., & Fuhrer, C. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3497-05.2005 · Cited by 152
Bellinger, D. L., Lorton, D., Hamill, R. W., Felten, S. Y., & Felten, D. L. (1993) · Brain Behavior and Immunity · doi:10.1006/brbi.1993.1021 · Cited by 148
Thayer, J. F., & Fischer, J. E. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.02023.x · Cited by 146
Origin of noradrenergic innervation of the spleen in rats
Bellinger, D. L., Felten, S. Y., Lorton, D., & Felten, D. L. (1989) · Brain Behavior and Immunity · doi:10.1016/0889-1591(89)90029-9 · Cited by 146 · cited 1×
“Vagus nerve fibres form synapses on these cell bodies in the coeliac ganglio”
BackgroundThe protective effect of the vagus nerve in a murine model of chronic relapsing colitis
Ghia, J., Blennerhassett, P. A., El–Sharkawy, R. T., & Collins, S. M. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00240.2007 · Cited by 126
Stimulated Production of Proinflammatory Cytokines Covaries Inversely With Heart Rate Variability
Marsland, A. L., Gianaros, P. J., Prather, A. A., Jennings, J. R., Neumann, S. A., & Manuck, S. B. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181576118 · Cited by 122
Davis, C. N., Mann, E., Behrens, M. M., Gaidarova, S., Rebek, M., REBEK, J. J., & Bartfai, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510802103 · Cited by 113 · cited 1×
“This complex associates with myeloid differentiation primary response protein 88 (MYD88; a cytoplasmic Toll–IL-1R (TIR) domain-containing adaptor protein) and recruits signalling proteins that activate mitogen-activated protein kinases (MAPKs) and nuclear factor-κB ( NF-κB”
BackgroundVagus nerve integrity and experimental colitis
Ghia, J., Blennerhassett, P. A., & Collins, S. M. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00098.2007 · Cited by 113
Hamano, R., Takahashi, H. K., Iwagaki, H., Yoshino, T., Nishibori, M., & Tanaka, N. (2006) · Shock · doi:10.1097/01.shk.0000228168.86845.60 · Cited by 111
Aerobic exercise attenuates inducible TNF production in humans
Sloan, R. P., Shapiro, P. A., DeMeersman, R. E., McKinley, P. S., Tracey, K. J., Slavov, I., Fang, Y., & Flood, P. D. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00147.2007 · Cited by 109
Self-citationRole of substance P in hydrogen sulfide-induced pulmonary inflammation in mice
Bhatia, M., Liang, Z., Zhang, H., Ng, S.-W., & Moore, P. K. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00053.2006 · Cited by 103 · cited 1×
“For example, the interaction of substance P with neurokinin 1 receptors, and the interaction of noradrenaline with α-adrenergic receptors, stimulates pro-inflammatory cytokine releas”
BackgroundLanza, G. A., Sgueglia, G. A., Cianflone, D., Rebuzzi, A. G., Angeloni, G., Sestito, A., Infusino, F., Crea, F., & Maseri, A. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.01.029 · Cited by 97
Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings
Labiner, D. M., & Ahern, G. L. (2006) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2006.00732.x · Cited by 92 · cited 1×
“Vagus nerve stimulators are currently in clinical use and have been safely implanted in tens of thousands of patients as a treatment for seizure disorders that are refractory to medicatio”
BackgroundCardiac Autonomic Changes Associated With Fish Oil vs Soy Oil Supplementation in the Elderly
Holguín, F., Téllez‐Rojo, M. M., Lazo, M., Mannino, D. M., Schwartz, J. D., Hernández, M., & Romieu, I. (2005) · CHEST Journal · doi:10.1016/s0012-3692(15)34453-6 · Cited by 86
Yoshimura, T., Kurita, C., Nagao, T., Usami, E., Nakao, T., Watanabe, S., Kobayashi, J., Yamazaki, F., Tanaka, H., Inagaki, N., et al. (2008) · Pharmacology · doi:10.1159/000139481 · Cited by 72 · cited 1×
“By contrast, activation of 5-hydroxytryptamine receptors or β-adrenergic receptors inhibits pro-inflammatory cytokine release and suppresses inflammatio”
BackgroundFunctional significance of coactivation of vagal and sympathetic cardiac nerves.
Koizumi, K., Terui, N., Kollai, M., & Brooks, C. M. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.6.2116 · Cited by 63 · cited 1×
“This occurs because parasympathetic stimulation slows the heart rate, which improves the efficiency by which the heart is filled with bloo”
BackgroundAcetylcholine and the sympathetic innervation of the spleen
Brandon, K. W., & Rand, M. J. (1961) · The Journal of Physiology · doi:10.1113/jphysiol.1961.sp006702 · Cited by 63
Straub, R. H., Rauch, L., Faßold, A., Lowin, T., & Pongratz, G. (2008) · Arthritis & Rheumatism · doi:10.1002/art.24030 · Cited by 62
von Känel, R., Nelesen, R. A., Mills, P. J., Ziegler, M. G., & Dimsdale, J. E. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.09.009 · Cited by 61
Jae, S. Y., Fernhall, B., Heffernan, K. S., Jeong, M., Chun, E. M., Sung, J., Lee, S. H., Lim, Y. J., & Park, W. H. (2006) · Metabolism · doi:10.1016/j.metabol.2006.02.010 · Cited by 60
Klimaschewski, L. P., Kummer, W., & Heym, C. (1996) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(19960901)35:1 · Cited by 55
Zhang, P., Han, D., Tang, T., Zhang, X., & Dai, K. (2008) · Inflammation Research · doi:10.1007/s00011-008-8070-1 · Cited by 52
Sympathetic Nervous System-Immune Interactions in Autoimmune Lymphoproliferative Diseases
del Rey, A., & Besedovsky, H. O. (2008) · NeuroImmunoModulation · doi:10.1159/000135621 · Cited by 44
Is innervation an early target in autoimmune diabetes?
Saravia, F., & Homo‐Delarche, F. (2003) · Trends in Immunology · doi:10.1016/j.it.2003.09.010 · Cited by 41
Reduction in heart rate variability in patients with systemic lupus erythematosus.
Laversuch, C. J., Seo, H., Modarres, H., Collins, D., McKenna, W. J., & Bourke, B. E. (1997) · PubMed · Cited by 40
Heart rate variability in patients with systemic lupus erythematosus
Stein, K., McFarlane, I., Goldberg, N., & Ginzler, E. M. (1996) · Lupus · doi:10.1177/096120339600500109 · Cited by 38
Ferri, C. C., Yuill, E. A., & Ferguson, A. V. (2005) · Regulatory Peptides · doi:10.1016/j.regpep.2005.01.004 · Cited by 37
The immunosuppressive effects of nicotine during human mixed lymphocyte reaction
Takahashi, H. K., Iwagaki, H., Hamano, R., Kanke, T., Liu, K., Sadamori, H., Yagi, T., Yoshino, T., Tanaka, N., & Nishibori, M. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.12.003 · Cited by 31 · cited 1×
“Activation of these mechanisms has been implicated in decreasing the expression of adhesion molecules, cytokine production and lymphocyte proliferatio”
BackgroundTHE CHOLINERGIC COMPONENT IN THE SYMPATHETIC INNERVATION TO THE SPLEEN
Leaders, F. E., & Dayrit, C. (1965) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)26964-6 · Cited by 28
Vagal stimulation suppresses ischemia-induced myocardial interstitial myoglobin release
Kawada, T., Yamazaki, T., Akiyama, T., Kitagawa, H., Shimizu, S., Mizuno, M., Li, M., & Sugimachi, M. (2008) · Life Sciences · doi:10.1016/j.lfs.2008.07.013 · Cited by 23
Muscarinic modulation of hypoxia-induced release of catecholamines from the cat carotid body
Wang, H.-Y. J., & Fitzgerald, R. S. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03334-0 · Cited by 19 · cited 1×
“These neurotransmitters cause depolarization of nearby sensory fibres travelling in the vagus nerve, which propagate to the brain stem, where a motor arc is activated to mediate compensatory responses to increase oxygen deliver”
BackgroundHeart Rate Variability in Patients with Systemic Sarcoidosis
Uslu, N., Akyol, A., Görgülü, Ş., Eren, M., Ocaklı, B., Çelık, S., Yildirim, A., Aksu, H., & Nurkalem, Z. (2006) · Annals of Noninvasive Electrocardiology · doi:10.1111/j.1542-474x.2006.00080.x · Cited by 17
Characterization of Choline O-Acetyltransferase (ChAT) in the BALB/C Mouse Spleen
Bulloch, K., Damavandy, T., & Badamchian, M. (1994) · International Journal of Neuroscience · doi:10.3109/00207459408985999 · Cited by 14 · cited 1×
“How can there be a requirement for α7nAChR-dependent signalling to control cytokine production in the spleen if the splenic neurons release catecholamines , not acetylcholine? It has been known for decades that the spleen is a rich source of acetylcholine (indeed, this molecule was originally identified in spleen tiss…”
Background濱野, 亮. (2007) · Institutional Repositories DataBase (IRDB) · Cited by 2
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Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
Air pollution: mechanisms of neuroinflammation and CNS disease
Block, M. L., & Calderón‐Garcidueñas, L. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.009 · Cited by 1,676
The interplay between the intestinal microbiota and the brain
Collins, S. M., Surette, M., & Bercik, P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2876 · Cited by 1,611
HMGB1 is a therapeutic target for sterile inflammation and infection
Andersson, U., & Tracey, K. J. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101323 · Cited by 1,437
Self-citationSepsis: pathophysiology and clinical management
Gotts, J. E., & Matthay, M. A. (2016) · BMJ · doi:10.1136/bmj.i1585 · Cited by 1,308
Metadata
- Authors
- Tracey, K. J.
- Affiliations
- Feinstein Institute for Medical Research (US)
- Corresponding author
- Tracey, Kevin J.
- ORCID
- Tracey, Kevin J.
- Venue
- Nature Reviews Immunology
- Published
- 2009-06
- Volume
- 9
- Issue
- 6
- Pages
- 418-428
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC4535331
- OpenAlex
- W2029051866
- Cited by
- 1,154
- References
- 102
- Citations by year
- 2026: 55 · 2025: 61 · 2024: 49 · 2023: 66 · 2022: 71 · 2021: 77 · 2020: 73 · 2019: 71 · 2018: 66 · 2017: 71 · 2016: 80 · 2015: 75 · 2014: 70 · 2013: 81 · 2012: 68
- FWCI
- 4.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Feinstein Institutes for Medical Research
- National Institute of General Medical Sciences (R01GM057226)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- cholinergic anti-inflammatory pathway, acetylcholine, inflammatory cytokines, neural circuits, innate immunity, neuroimmune regulation, inflammatory diseases
- MeSH terms
- Animals, Cardiovascular Physiological Phenomena, Catecholamines, Efferent Pathways, Homeostasis, Humans, Hypertension, Immunity, Innate, Inflammation, Receptors, Cholinergic, Reflex, Neuroimmunomodulation
About these checks
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