Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-22T11:48:19.179Z Has data issue: false hasContentIssue false

Chapter 2 - From Psychoneuroimmunology to Immunopsychiatry: An Historical Perspective

Published online by Cambridge University Press:  02 September 2021

By
Keith W. Kelley
Edited by
Golam Khandaker ,
Neil Harrison ,
Edward Bullmore  and
Robert Dantzer
Golam Khandaker
Affiliation:
University of Cambridge
Neil Harrison
Affiliation:
Cardiff University Brain Research Imaging Centre (CUBRIC)
Edward Bullmore
Affiliation:
University of Cambridge
Robert Dantzer
Affiliation:
University of Texas, MD Anderson Cancer Center
Get access

Summary

      It was the best of times, it was the worst of times,
      it was the age of wisdom, it was the age of foolishness,
      it was the epoch of belief, it was the epoch of incredulity,
      it was the season of Light, it was the season of Darkness,
      it was the spring of hope, it was the winter of despair …
    Charles Dickens, A Tale of Two Cities, 1859
Following Great Britain’s loss of the American Revolutionary War in 1783, the industrial revolution continued to prop up King George III in London. In Paris, the other major city in Dickens’ novel, it was the best of times for King Louis XVI and his queen, Marie Antoinette. They had a palace at Versailles and enormous wealth. But it soon become the worst of times for them and other bourgeoisie with the beginning of the French Revolution in 1789 and continuing through the Reign of Terror that ended in 1794. Nearly two centuries later in 1989, it was worst of times for the fledging field of psychoneuroimmunology (PNI). But now it is the best of times for this field that emphasizes an integrative physiological approach to biomedical research. This renaissance in PNI has laid a solid brick-and-mortar foundation for the emerging field of immunopsychiatry. Indeed, before one can understand the importance of the emerging field of immunopsychiatry, one must first grasp the historical developments of PNI. The best and worst of times for immunopsychiatry has yet to be written. Laissez les bon temps rouler!

Type
Chapter
Information
Textbook of Immunopsychiatry , pp. 25 - 50
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Solomon, GF. Psychoneuroimmunologic approaches to research on AIDS. Ann NY Acad Sci. 1987;496:628–36.Google Scholar
Kiecolt-Glaser, JK, Glaser, R. Psychological influences on immunity: implications for AIDS. Amer Psychol. 1988;43:892–8.CrossRefGoogle ScholarPubMed
Sturdevant, CB, Joseph, SB, Schnell, G, et al. Compartmentalized replication of R5 T Cell-Tropic HIV-1 in the central nervous system early in the course of infection. PLOS Pathogens. 2015. doi.org/10.1371/journal.ppat.1004720Google Scholar
Rapuoli, R, Santoni, A, Mantovani, A. Vaccines: an achievement of civilization, a human right, our health insurance for the future. J Exp Med. 2018;216:7–9.Google Scholar
Ader, R. Psychosomatic and psychoimmunologic research. Psychosomatic Research. 1980;42;307–21.Google Scholar
Janković, BD. From immunoneurology to immunopsychiatry: neuromodulating activity of anti-brain antibodies. Int Rev Neurobiol. 1985;26:249–314.CrossRefGoogle ScholarPubMed
Kelley, KW. Norman Cousins lecture. From hormones to immunity: the physiology of immunology. Brain Behav Immun. 2004;18:95–113.Google Scholar
Benowitz, S. Psychoneuroimmunology finds acceptance as science adds evidence. The Scientist. 1996. www.the-scientist.com/research/psychoneuroimmunology-finds-acceptance-as-science-adds-evidence-57912Google Scholar
Carson, MJ, Lo, DD. Perspective is everything: an irreverent discussion of CNS-immune system interactions as viewed from different scientific traditions. Brain Behav Immun. 2007;21:367–73.CrossRefGoogle ScholarPubMed
Institute of Medicine. Capturing Social and Behavioral Domains and Measures in Electronic Health Records. Phase 2. Washington, DC, National Academies Press; 2014.Google Scholar
Pantell, MS, Prather, AA, Downing, JM, et al. Association of social and behavioral risk factors with earlier onset of adult hypertension and diabetes. JAMA Network Open. 2019;2:e193933. doi:10.17226/18951Google Scholar
Anonymous. The expanding role of hospital medicine and the co-management of patients. In Focus, FOJP Service Corporation. 2013;21:1–20. https://hicgroup.com/sites/default/files/InFocus_Spring13_0.pdfGoogle Scholar
National Public Radio. Timeline. 2006. http://thenewmedicine.org/timeline.htmlGoogle Scholar
Solomon, GF, Moss, RH. Emotions, immunity, and disease; a speculative theoretical integration. Arch Gen Psychiatry. 1964;11:657–74.CrossRefGoogle ScholarPubMed
Kelley, KW. Stress and immune function: a bibliographic review. Ann Rech Vet. 1980; 11:445–78.Google Scholar
Ader, R. Psychoneuroimmunology. Academic Press, New York; 1981;1–688.Google Scholar
Spector, NH, Korneva, EA. Neurophysiology, immunophysiology and neuroimmunomodulation. In Ader, R, ed. Psychoneuroimmunology. Academic Press, New York; 1981:449–69.Google Scholar
Korneva, EA. Beginnings and main directions of psychoneuroimmunology. International Journal of Psychophysiology. 1989;7:1–18.Google Scholar
Moyers, B. Healing & the mind. 1993. https://billmoyers.com/series/healing-and-the-mind/Google Scholar
Pariante, CM. Psychoneuroimmunology or immunopsychiatry. The Lancet Psychiatry. 2015;2:197–8.CrossRefGoogle ScholarPubMed
Korneva, EA. On the history of immunophysiology: first steps and main trends. In Berczi, I, ed. New Insights to Neuroimmune Biology. Elsevier, Amsterdam; 2010:33–50.CrossRefGoogle Scholar
Kerza-Kwiatecki, AP. Conference report. First international workshop on neuroimmunomodulation (NIM). J Neuroimmunol. 1985;10:97–9.Google Scholar
Pirzgalska, RM, Seixas, E, Seidman, JS, et al. Sympathetic neuron–associated macrophages contribute to obesity by importing and metabolizing norepinephrine. Nature Medicine. 2017;23:1309–18.Google Scholar
Cohen, JJ. Methodological issues in behavioural immunology. Immunology Today. 1987;8:33–4.Google Scholar
Laudenslager, ML. Research perspectives in psychoneuroimmunology IV, 1993. Psychoneuroendocrinology. 1994;19:751–63.Google Scholar
Kelley, KW. Presidential Address: it’s time for psychoneuroimmunology. Brain Behav Immun. 2001;15:1–6.Google Scholar
Anonymous. Past meeting sites. 2019a. https://pnirs.org/meetings/pastmeetings.cfmGoogle Scholar
Kelley, KW. To boldly go where no one has gone before. Brain Behav Immun. 2017;66:1–8.Google Scholar
Kelley KW, Peng, YP, Liu Q, et al. PsychoNeuroImmunology goes east: Development of the PNIRS China affliate and its expansion into PNIRS Asia-Pacific. Brain Behav Immun 88:75–87. doi.org/10.1016/j.bbi.2020.04.026.Google Scholar
Anonymous. Neural-immune axis. Reciprocal regulation in development, health and disease. 2019c. www.cell-symposia.com/neuroimmunology-2019Google Scholar
Ader, R, Cohen, N, Felten, DL. Editorial: brain, behavior, and immunity. Brain Behav Immun. 1987;1:1–6.Google Scholar
Petry, NM, Barry, D, Pietrzak, RH, et al. Overweight and obesity are associated with psychiatric disorders: results from the national epidemiologic survey on alcohol and related conditions. Psychosom Med. 2008;70:288–97.CrossRefGoogle ScholarPubMed
Blalock, JE. The immune system as a sensory organ. J Immunol. 1984;132:1067–70.Google Scholar
Kipnis, J. Immune system. The ‘seventh sense’. J Exp Med. 2018;215:397–8.Google Scholar
Konsman, JP. Inflammation and depression: a nervous plea for psychiatry to not become immune to interpretation. Pharmaceuticals. 2019;12:29. https://doi.org/10.3390/ph12010029Google Scholar
Stein, M, Miller, AH, Trestman, RL. Depression, the immune system, and health and illness. Arch Gen Psychiatry. 1991;48:171–7.Google Scholar
Stein, M. Future directions for brain, behavior, and the immune system. Bull NY Acad Med. 1992;68:390–410.Google Scholar
Kelley, KW, Weigent, DA, Kooijman, R.. Protein hormones and immunity. Brain Behav Immun. 2007;21:384–92.Google Scholar
Farhat, K, Bodart, G, Charlet-Renard, C, et al. Growth hormone (GH) deficient mice with GHRH gene ablation are severely deficient in vaccine and immune responses against Streptococcus pneumoniae. Front Immunol. 2018;9:1–15(article 2175).Google Scholar
Kiecolt-Glaser, JK, Glaser, R, Shuttleworth, EC, et al. Chronic stress and immunity in family caregivers of Alzheimer’s disease victims. Psychosom Med. 1987;49:523–35.Google Scholar
Wilson, SJ, Padin, AC, Birmingham, DJ, et al. When distress becomes somatic: dementia family caregivers’ distress and genetic vulnerability to pain and sleep Problems. Gerontologist. 2018. doi:10.1093/geront/gny150Google Scholar
Irwin, MR, Olmstead, R, Oxman, MN. Augmenting immune responses to varicella zoster virus in older adults: a randomized, controlled trial of Tai Chi. J Am Geriatr Soc. 2007;55:511–17.Google Scholar
Irwin, MR, Olmstead, R, Carrillo, C, et al. Tai chi chih compared with cognitive behavioral therapy for the treatment of insomnia in survivors of breast cancer: a randomized, partially blinded, noninferiority trial. J Clin Oncol. 2017;35:2656–65.Google Scholar
Lavretsky, H, Altstein, LL, Olmstead, RE, et al. Complementary use of Tai chi chih augments escitalopram treatment of geriatric depression: a randomized controlled trial. Am J Geriatr Psychiatry. 2011;19:839–50.Google Scholar
Berkenbosch, F, van Oers, J, del Rey, A, et al. Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science. 1987;238:524–6.CrossRefGoogle ScholarPubMed
Sapolsky, R, Rivier, C, Yamamoto, G, et al. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science. 1987;238:522–4.Google Scholar
Morrissey, PJ, Charrier, K, Alpert, A, et al. In vivo administration of IL-1 induces thymic hypoplasia and increased levels of serum corticosterone. J Immunol. 1988;141:1456–63.Google Scholar
Dantzer, R, Kelley, KW. Stress and immunity: An integrated view of relationships between the brain and the immune system. Life Sciences. 1989;44:1995–2008.Google Scholar
Shimabukuro-Vornhagen, A, Godel, P, Subklewe, M, et al. Cytokine release syndrome. J ImmunoTherapy of Cancer. 2018;6 56. doi: 10.1186/s40425-018-0343-9Google Scholar
Goetzl, EJ. Forward. J Immunol. 1985; 135:738. doi: 10.1186/s40425-018-0343-9Google Scholar
Stein, M, Keller, SE, Schleifer, SJ. Stress and immunomodulation: the role of depression and neuroendocrine function. J Immunol. 1985;135:827–33.Google Scholar
Irwin, MR. The “P” in PNIRS – A discussion over beer. 2004. https://pnirs.org/resources/docs/Program%20Booklet%202004.pdfGoogle Scholar
Marsland, A, Walsh, C Lockwood, K, et al. The effects of acute of psychological stress on circulating and stimulated inflammatory markers: A systematic review and meta-analysis. Brain Behav Immun, 2017;64:208–19.Google Scholar
Wan, W, Janz, L, Vriend, CY, et al. Differential induction of c-Fos immunoreactivity in hypothalamus and brain stem nuclei following central and peripheral administration of endotoxin. Brain Res Bull. 1993;32:581–7.Google Scholar
Wan, W, Wetmore, L, Sorensen, C, et al. Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain. Brain Res Bull. 1994;34:7–14.Google Scholar
Bluthé, RM, Walter, V, Parnet, P, et al. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad Sci III. 1994;317:499–503.Google Scholar
Watkins, LR, Wiertelak, EP, Goehler, LE, et al. Neurocircuitry of illness-induced hyperalgesia. Brain Res. 1994;639:283–99.Google Scholar
Fleshner, M, Goehler, LE, Hermann, J, et al. Interleukin-1 beta induced corticosterone elevation and hypothalamic NE depletion is vagally mediated. Brain Res Bull. 1995;37:605–10.CrossRefGoogle ScholarPubMed
Layé, S, Bluthé, RM, Kent, S, et al. Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS. Am J Physiol. 1995;268:R1327–31.Google Scholar
Bluthé, RM, Michaud, B, Kelley, KW, et al. Vagotomy blocks behavioural effects of interleukin-1 injected via the intraperitoneal route but not via other systemic routes. Neuroreport. 1996;7:2823–7.Google Scholar
Fülling, C, Dinan, TG, Cryan, JF. Gut microbe to brain signaling: What happens in vagus … Neuron. 2019;101:998–1002.Google Scholar
Hart, BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988;12 :123–137.Google Scholar
Kent, S, Bluthé, RM, Dantzer, R, et al. Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1. Proc Natl Acad Sci USA. 1992a;89:9117–20.Google Scholar
Kent, S, Bluthé, RM, Kelley, KW, et al. Sickness behavior as a new target for drug development TIPS. 1992b;13:24–28.Google Scholar
Yirmiya, R. Endotoxin produces a depressive-like episode in rats. Brain Research. 1996;711:163–74.CrossRefGoogle ScholarPubMed
Reichenberg, A, Yirmiya, R, Schuld, A, et al. Cytokine-mediated emotional and cognitive disturbances in humans. Archives of General Psychiatry. 2001;58:445–52.Google Scholar
Capuron, L, Ravaud, A. Prediction of the depressive effects of interferon alfa therapy by the patient’s initial affective state. N Engl J Med. 1999;340:1370.Google Scholar
Musselman, DL, Lawson, DH, Gumnick, JF, et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med. 2001;344:961–6.Google Scholar
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;160:1554–65.Google Scholar
Pace, TW, Hu, F, Miller, AH. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depressionBrain Behav Immun. 2007;21:9–19.Google Scholar
Hasselmann, H, Gamradt, S, Taenzer, A, et al. Pro-inflammatory monocyte phenotype and cell-specific steroid signalling alterations in unmedicated patients with major depressive disorder. Front Immunol. 2018;9:1–9(article 2693).Google Scholar
Hotamisligil, GS, Shargill, NS, Spiegelman, BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.Google Scholar
Niraula, A, Wang, Y, Godbout, JP, et al. Corticosterone production during repeated social defeat causes monocyte mobilization from the bone marrow, glucocorticoid resistance, and neurovascular adhesion molecule expression. J. Neuroscience. 2018;38:2338–40.Google Scholar
Xiao, P, Zhang, H, Zhang, Y, et al. Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10. J Exp Med. 2019:216(2):337–49. doi:10.1084/jem20181198Google Scholar
Cannon, W. The wisdom of the body. Physiol Rev. 1929;9:399–431.Google Scholar
Selye, H. Stress and the General Adaptation Syndrome. Br Med J. 1950;1:1383–92.Google Scholar
McEwen, BS, Stellar, E. Stress and the individual: mechanisms leading to disease. Arch Intern Med. 1993;153:2093–101.Google Scholar
McEwen, BS. Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychpharmacology. 1999;22:108–24.Google Scholar
Sterling, P, Eyer, J. Allostasis: A new paradigm to explain arousal pathology. In Fisher, S and Reason, J, eds. Handbook of Life Stress, Cognition and Health. John Wiley and Sons, New York; 1988;629–49.Google Scholar
Kelley, KW, Curtis, SE, Dantzer, R. Disease-environment interactions: Another contribution of Louis Pasteur. 2009. www.brainimmune.com/disease-environment-interactions-another-contribution-of-louis-pasteur-1878/Google Scholar
Previte, JJ, Berry, LJ. The effect of environmental temperature on the host–parasite relationship in mice. J Infect Dis. 1962;119:201–9.Google Scholar
Cohen, S, Tyrrell, DA, Smit, AP. Psychological stress and susceptibility to the common cold. N Engl J Med. 1991;325:606–12.Google Scholar
Caspi, A, Sugden, K, Moffitt, TE, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386–9.Google Scholar
Ban, E, Milon, G, Prudhomme, N, et al. Receptors for interleukin-1 (alpha and beta) in mouse brain: mapping and neuronal localization in hippocampus. Neuroscience. 1991;43:21–30.Google Scholar
Cunningham, ET, Jr Wada, E, Carter, DB, et al. Localization of interleukin-1 receptor messenger RNA in murine hippocampus. Endocrinology. 1991;28:2666–8.Google Scholar
Holmes, GM, Hebert SL, SL, Rogers, RC, et al. Immunocytochemical localization of TNF type 1 and type 2 receptors in the rat spinal cord. Brain Res. 2004;1025;210–19.Google Scholar
Wang, H, Yu, M, Ochani, M, et al. Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature. 2003;421:384–8.Google Scholar
O’Neill, LAJ, Golenbock, D, Bowie, AG. The history of Toll-like receptors – redefining innate immunity. Nature Reviews Immunology. 2013;13:453–60.Google Scholar
Matzinger, P. Tolerance, danger, and the extended family. Annual Review of Immunology. 1994;12:991–1045.Google Scholar
Seong, SY, Matzinger, P. Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nature Reviews Immunology. 2004;4:469–78.Google Scholar
Fleshner, M, Frank, M, Maier, SF. Danger signals and inflammasomes: stress-evoked sterile inflammation in mood disorders. Neuropsychopharmacology. 2017;42:36–45.Google Scholar
Faraj, TA, Stover, C, Erridge, C. Dietary toll-like receptor stimulants promote hepatic inflammation and impair reverse cholesterol transport in mice via macrophage-dependent interleukin-1 production. Front Immunol. 2019;10:1404. doi.org/10.3389/fimmu.2019.01404Google Scholar
Erickson, MA, Banks, WA. Neuroimmune axes of the blood–brain barriers and blood–brain interfaces: bases for physiological regulation, disease states, and pharmacological interventions. Pharmacol Rev. 2018;70:278–314.Google Scholar
Banks, WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov. 2016;15:275–92.Google Scholar
Stamatovic, SM, Shakui, P, Keep, RF, et al. Monocyte chemoattractant protein-1 regulation of blood-brain barrier permeability. J Cereb Blood Flow Metab. 2005;25:593–606.CrossRefGoogle ScholarPubMed
Kovac, A, Erickson, MA, Banks, WA. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide and LRP-1 expression in response to lipopolysaccharide. J Neuroinflammation. 2011;8:139. doi: 10.1186/1742-2094-8-139Google Scholar
Blank, T, Detje, CN, Spieß, A. et al. Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment. Immunity. 2016;44:901–12.Google Scholar
Korin, R, Ben-Shaanan, TL, Schiller, M, et al. High-dimensional, single-cell characterization of the brain’s immune compartment. Nat Neurosci. 2017;20:1300–9.Google Scholar
Mrdjen, D, Pavlovic, A, Hartmann, FJ. et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity. 2018;48:380–95.Google Scholar
Herz, J, Filiano, AJ, Smith, A, et al. Myeloid cells in the central nervous system. Immunity. 2017;6:943–56.Google Scholar
Galloway, DA, Phillips, AEM, Owen, DRJ, Moore, CS. Phagocytosis in the brain: homeostasis and disease. Frontiers in Immunology. 2019;10:1–15.Google Scholar
John, GR, Lee, SC, Brosnan, CF. Cytokines: powerful regulators of glial cell activation. Neuroscientist. 2003;9:10–22.Google Scholar
Cserr, HF, Harling-Berg, CJ Knopf, PM. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol. 1992;2:269–76.Google Scholar
Iliff, JJ, Wang, M, Liao, Y. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4:147ra111.1–11.Google Scholar
Louveau, A, Smirnov, I, Keyes, TJ. et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523:337–41.Google Scholar
Aspelund, A, Antila, S, Proulx, ST. et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015;212:991–9.Google Scholar
Louveau, A, Herz, J, Alme, MN, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018;21:1380–91.CrossRefGoogle ScholarPubMed
Antila, S, Karaman, S, Nurmi, H, et al. Development and plasticity of meningeal lymphatic vessels. J Exp Med. 2017;214:3645–67.Google Scholar
Felten, DL, Ackerman, KD, Wiegand, SJ, et al. 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.Google Scholar
Sanders, VM. The beta2-adrenergic receptor on T and B lymphocytes: do we understand it yet? Brain Behav Immun. 2012;26:195–200.Google Scholar
Shakhar, G, Ben-Eliyahu, S. In vivo beta-adrenergic stimulation suppresses natural killer activity and compromises resistance to tumor metastasis in rats. J Immunol. 1998;60:3251–8.Google Scholar
Schedlowski, M, Jacobs, R Stratmann, G, et al. Changes of natural killer cells during acute psychological stress. J Clin Immunol. 1993;13:119–26.Google Scholar
Walker, AK, Martelli, D, Ziegler, AL, et al. Circulating epinephrine is not required for chronic stress to enhance metastasis. Psychoneuroendocrinology. 2019;99:191–5.Google Scholar
Cui, B, Luo, Y, Tian, P, et al. Stress-induced epinephrine enhances lactate dehydrogenase A and promotes cancer stem-like cells. J Clin Invest. 2019;129:1030–46. doi.org/10.1172/JCI121685Google Scholar
Nance, DM, Hopkins, DA, Bieger, D. Re-investigation of the innervation of the thymus gland in mice and rats. Brain Behav Immun. 1987;1:134–47.Google Scholar
Borovikova, LV, Ivanova, S, Zhang, M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405:458–62.Google Scholar
Rosas-Ballina, M, Olofsson, PS, Ochani, M, et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011;334:98–101.Google Scholar
Olofsson, PS, Steinberg, BE, Sobb, R, et al. Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase. Nat Biotechnol. 2016;34:1066–71.Google Scholar
Huston, JM, Ochani, M, Rosas-Ballina, M, et al. Splenectomy inactivates the cholinergic anti-inflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med. 2006;203:1623–8.Google Scholar
Nance, DM, Sanders, VM. Autonomic innervation and regulation of the immune system. Brain Behav Immun. 2007;21:736–45.Google Scholar
Bratton, BO, Martelli, D, McKinley, MJ, et al. Neural regulation of inflammation: no neural connection from the vagus to splenic sympathetic neurons. Exp Physiol. 2012;97:1180–5.Google Scholar
Marteelli, D, McKinley, MJ, McAllen, RM. The cholinergic anti-inflammatory pathway: A critical review. Antonomic Neuroscience: Basic and Clinical. 2014;182:65–9.Google Scholar
Gautron, L, Rutkowski, JM, Burton, MD, et al. Neuronal and nonneuronal cholinergic structures in the mouse gastrointestinal tract and spleen. J Comp Neurol. 2013;521:3741–67.Google Scholar
Komegae, EN, Farmer, DGS, Brooks, VL, et al. Vagal afferent activation suppresses systemic inflammation via the splanchnic anti-inflammatory pathway. Brain Behav Immun. 2018;73:441–9.Google Scholar
Kelley, KW. Immunological consequences of changing environmental stimuli. In Moberg, GP, ed. Animal Stress. Bethesda, MD: American Physiological Society; 1985:193–233.Google Scholar
Guttenplan, KA, Liddelow, SA. Astrocytes and microglia: models and tools. J Exp Med. 2019;216(1):71–83. http://doi.org/10.1084/jem.20180200Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×