Today: May 26, 2024
Last update: May 3, 2024
Dysfunction of the Autonomic Nervous System and Its Role in the Pathogenesis of Septic Critical Illness (Review)

Dysfunction of the Autonomic Nervous System and Its Role in the Pathogenesis of Septic Critical Illness (Review)

Kiryachkov Y.Y., Bosenko S.A., Muslimov B.G., Petrova M.V.
Key words: autonomic nervous system; sepsis; cholinergic anti-inflammatory pathway.
2020, volume 12, issue 4, page 106.

Full text

html pdf

Dysfunction of the autonomic nervous system (ANS) of the brain in sepsis can cause severe systemic inflammation and even death. Numerous data confirmed the role of ANS dysfunction in the occurrence, course, and outcome of systemic sepsis. The parasympathetic part of the ANS modifies the inflammation through cholinergic receptors of internal organs, macrophages, and lymphocytes (the cholinergic anti-inflammatory pathway). The sympathetic part of ANS controls the activity of macrophages and lymphocytes by influencing β2-adrenergic receptors, causing the activation of intracellular genes encoding the synthesis of cytokines (anti-inflammatory beta2-adrenergic receptor interleukin-10 pathway, β2AR–IL-10). The interaction of ANS with infectious agents and the immune system ensures the maintenance of homeostasis or the appearance of a critical generalized infection. During inflammation, the ANS participates in the inflammatory response by releasing sympathetic or parasympathetic neurotransmitters and neuropeptides. It is extremely important to determine the functional state of the ANS in critical conditions, since both cholinergic and sympathomimetic agents can act as either anti- or pro-inflammatory stimuli.

  1. Williams D.P., Koenig J., Carnevali L., Sgoifo A., Jarczok M.N., Sternberg E.M., Thayer J.F. Heart rate variability and inflammation: a meta-analysis of human studies. Brain Behav Immun 2019; 80: 219–226,
  2. Werdan K., Schmidt H., Ebelt H., Zorn-Pauly K., Koidl B., Hoke R.S., Heinroth K., Müller-Werdan U. Impaired regulation of cardiac function in sepsis, SIRS, and MODS. Can J Physiol Pharmacol 2009; 87(4): 266–274,
  3. Raithel D.S., Ohler K.H., Porto I., Bicknese A.R., Kraus D.M. Morphine: an effective abortive therapy for pediatric paroxysmal sympathetic hyperactivity after hypoxic brain injury. J Pediatr Pharmacol Ther 2015; 20(4): 335–340.
  4. Baguley I.J., Perkes I.E., Fernandez-Ortega J.F., Rabinstein A.A., Dolce G., Hendricks H.T.; Consensus Working Group. Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on conceptual definition, nomenclature, and diagnostic criteria. J Neurotrauma 2014; 31(17): 1515–1520,
  5. Esterov D., Greenwald B.D. Autonomic dysfunction after mild traumatic brain injury. Brain Sci 2017; 7(8): E100,
  6. Wang D.W., Yin Y.M., Yao Y.M. Vagal modulation of the inflammatory response in sepsis. Int Rev Immunol 2016; 35(5): 415–433,
  7. Zila I., Mokra D., Kopincova J., Kolomaznik M., Javorka M., Calkovska A. Vagal-immune interactions involved in cholinergic anti-inflammatory pathway. Physiol Res 2017; 66(Suppl 2): S139–S145,
  8. Huang Y., Zhao C., Su X. Neuroimmune regulation of lung infection and inflammation. QJM 2019; 112(7): 483–487,
  9. Ren C., Li X.H., Wang S.B., Wang L.X., Dong N., Wu Y., Yao Y.M. Activation of central alpha 7 nicotinic acetylcholine receptor reverses suppressed immune function of T lymphocytes and protects against sepsis lethality. Int J Biol Sci 2018; 14(7): 748–759,
  10. Reyes-Lagos J.J., Ledesma-Ramírez C.I., Pliego-Carrillo A.C., Peña-Castillo M.Á., Echeverría J.C., Becerril-Villanueva E., Pavón L., Pacheco-López G. Neuroautonomic activity evidences parturition as a complex and integrated neuro-immune-endocrine process. Ann N Y Acad Sci 2018; 1437(1): 22–30,
  11. Qian Y.S., Zhao Q.Y., Zhang S.J., Zhang Y.J., Wang Y.C., Zhao H.Y., Dai Z.X., Tang Y.H., Wang X., Wang T., Huang C.X. Effect of α7nAChR mediated cholinergic anti-inflammatory pathway on inhibition of atrial fibrillation by low-level vagus nerve stimulation. Zhonghua Yi Xue Za Zhi 2018; 98(11): 855–859,
  12. Murray K., Reardon C. The cholinergic anti-inflammatory pathway revisited. Neurogastroenterol Motil 2018; 30(3),
  13. Yamada M., Ichinose M. The cholinergic anti-inflammatory pathway: an innovative treatment strategy for respiratory diseases and their comorbidities. Curr Opin Pharmacol 2018; 40: 18–25,
  14. Pavlov V.A., Ochani M., Yang L.H., Gallowitsch-Puerta M., Ochani K., Lin X., Levi J., Parrish W.R., Rosas-Ballina M., Czura C.J., Larosa G.J., Miller E.J., Tracey K.J., Al-Abed Y. Selective α7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med 2007; 35(4): 1139–1144,
  15. Lu J., Goh S.J., Tng P.Y., Deng Y.Y., Ling E.A., Moochhala S. Systemic inflammatory response following acute traumatic brain injury. Front Biosci (Landmark Ed) 2009; 14: 3795–3813,
  16. Shin S.S., Dixon C.E. Alterations in cholinergic pathways and therapeutic strategies targeting cholinergic system after traumatic brain injury. J Neurotrauma 2015; 32(19): 1429–1440,
  17. Liu Q., Xie J., Yang Y. Advances in the regulation mechanism of cholinergic anti-inflammatory pathway on sepsis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019; 31(6): 781–784,
  18. Guyot M., Simon T., Panzolini C., Ceppo F., Daoudlarian D., Murris E., Macia E., Abélanet S., Sridhar A., Vervoordeldonk M.J., Glaichenhaus N., Blancou P. Apical splenic nerve electrical stimulation discloses an anti-inflammatory pathway relying on adrenergic and nicotinic receptors in myeloid cells. Brain Behav Immun 2019; 80: 238–246,
  19. Noh H., Yu M.R., Kim H.J., Lee J.H., Park B.W., Wu I., Matsumoto M., King G.L. Beta 2 adrenergic receptor agonists are novel regulators of macrophage activation in diabetic renal and cardiovascular complications. Kidney Int 2017; 92(1): 101–113,
  20. Lechtenberg K.J., Meyer S.T., Doyle J.B., Peterson T.C., Buckwalter M.S. Augmented β2-adrenergic signaling dampens the neuroinflammatory response following ischemic stroke and increases stroke size. J Neuroinflammation 2019; 16(1): 112,
  21. Zabrodskii P.F., Gromov M.S., Maslyakov V.V. Combined effect of NF-κB inhibitor and β2-adrenoreceptor agonist on mouse mortality and blood concentration of proinflammatory cytokines in sepsis. Bull Exp Biol Med 2018; 165(4): 445–448,
  22. Sun J.J., Lan J.F., Zhao X.F., Vasta G.R., Wang J.X. Binding of a C-type lectin’s coiled-coil domain to the Domeless receptor directly activates the JAK/STAT pathway in the shrimp immune response to bacterial infection. PLoS Pathog 2017; 13(9): e1006626,
  23. Ruiz-Medina B.E., Cadena-Medina D.A., Esparza E., Arrieta A.J., Kirken R.A. Isoproterenol-induced beta-2 adrenergic receptor activation negatively regulates interleukin-2 signaling. Biochem J 2018; 475(18): 2907–2923,
  24. Wu H., Li L., Su X. Vagus nerve through α7 nAChR modulates lung infection and inflammation: models, cells, and signals. Biomed Res Int 2014; 2014: 283525,
  25. Vaughn A.C., Cooper E.M., DiLorenzo P.M., O’Loughlin L.J., Konkel M.E., Peters J.H., Hajnal A., Sen T., Lee S.H., de La Serre C.B., Czaja K. Energy-dense diet triggers changes in gut microbiota, reorganization of gut brain vagal communication and increases body fat accumulation. Acta Neurobiol Exp (Wars) 2017; 77(1): 18–30,
  26. Cawthon C.R., de La Serre C.B. Gut bacteria interaction with vagal afferents. Brain Res 2018; 1693 (Pt B): 134–139,
  27. Bonaz B., Sinniger V., Pellissier S. Vagus nerve stimulation at the interface of brain-gut interactions. Cold Spring Harb Perspect Med 2019; 9(8): a034199,
  28. Houlden A., Goldrick M., Brough D., Vizi E.S., Lenart N., Martinecz B., Roberts I.S., Denes A. Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production. Brain Behav Immun 2016; 57: 10–20,
  29. Kigerl K.A., Mostacada K., Popovich P.G. Gut microbiota are disease-modifying factors after traumatic spinal cord injury. Neurotherapeutics 2018; 15(1): 60–67,
  30. de Jonge W.J. The gut’s little brain in control of intestinal immunity. ISRN Gastroenterol 2013; 2013: 630159,
  31. Radmark L., Sidorchuk A., Osika W., Niemi M. A systematic review and meta-analysis of the impact of mindfulness based interventions on heart rate variability and inflammatory markers. J Clin Med 2019; 8(10): E1638,
  32. Sharma V.K., Savitha S., Vinod K.V., Rajappa M., Subramanian S.K., Rajendran R. Assessment of autonomic functions and its association with telomerase level, oxidative stress and inflammation in complete glycemic spectrum — an exploratory study. Diabetes Metab Syndr 2019; 13(2): 1193–1199,
  33. Pong J.Z., Fook-Chong S., Koh Z.X., Samsudin M.I., Tagami T., Chiew C.J., Wong T.H., Ho A.F.W., Ong M.E.H., Liu N. Combining heart rate variability with disease severity score variables for mortality risk stratification in septic patients presenting at the emergency department. Int J Environ Res Public Health 2019; 16(10): E1725,
  34. Rupprecht S., Finn S., Hoyer D., Guenther A., Witte O.W., Schultze T., Schwab M. Association between systemic inflammation, carotid arteriosclerosis, and autonomic dysfunction. Transl Stroke Res 2020; 11(1): 50–59,
  35. Magrone T., Jirillo E. Sepsis: from historical aspects to novel vistas. pathogenic and therapeutic considerations. Endocr Metab Immune Disord Drug Targets 2019; 19(4): 490–502,
  36. Kanashiro A., Sônego F., Ferreira R.G., Castanheira F.V., Leite C.A., Borges V.F., Nascimento D.C., Cólon D.F., Alves-Filho J.C., Ulloa L., Cunha F.Q. Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis. Pharmacol Res 2017; 117: 1–8,
  37. Assinger A., Schrottmaier W.C., Salzmann M., Rayes J. Platelets in sepsis: an update on experimental models and clinical data. Front Immunol 2019; 10: 1687,
  38. Vergadi E., Vaporidi K., Tsatsanis C. Regulation of endotoxin tolerance and compensatory anti-inflammatory response syndrome by non-coding RNAs. Front Immunol 2018; 9: 2705,
  39. Quek A.M.L., Britton J.W., McKeon A., So E., Lennon V.A., Shin C., Klein C., Watson R.E., Kotsenas A.L., Lagerlund T.D., Cascino G.D., Worrell G.A., Wirrell E.C., Nickels K.C., Aksamit A.J., Noe K.H., Pittock S.J. Autoimmunne epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol 2012; 69(5): 582–593,
  40. Bauer J., Becker A.J., Elyaman W., Peltola J., Rüegg S., Titulaer M.J., Varley J.A., Beghi E. Innate and adaptive immunity in human epilepsies. Epilepsia 2017; 58(Suppl 3): 57–68,
  41. Golden E.P., Vernino S. Autoimmune autonomic neuropathies and ganglionopathies: epidemiology, pathophysiology, and therapeutic advances. Clin Auton Res 2019; 29(3): 277–288,
  42. Gaddam S.S., Buell T., Robertson C.S. Systemic manifestations of traumatic brain injury. Handb Clin Neurol 2015; 127: 205–218,
  43. Frasch M.G., Szynkaruk M., Prout A.P., Nygard K., Cao M., Veldhuizen R., Hammond R., Richardson B.S. Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway? J Neuroinflammation 2016; 13(1): 103,
  44. Nicholls A.J., Wen S.W., Hall P., Hickey M.J., Wong C.H.Y. Activation of the sympathetic nervous system modulates neutrophil function. J Leukoc Biol 2018; 103(2): 295–309,
  45. Oikawa S., Kai Y., Mano A., Sugama S., Mizoguchi N., Tsuda M., Muramoto K., Kakinuma Y. Potentiating a non-neuronal cardiac cholinergic system reinforces the functional integrity of the blood brain barrier associated with systemic anti-inflammatory responses. Brain Behav Immun 2019; 81: 122–137,
  46. Boeckxstaens G. The clinical importance of the anti-inflammatory vagovagal reflex. Handb Clin Neurol 2013; 117: 119–134,
  47. Nunes N.S., Chandran P., Sundby M., Visioli F., da Costa Gonçalves F., Burks S.R., Paz A.H., Frank J.A. Therapeutic ultrasound attenuates DSS-induced colitis through the cholinergic anti-inflammatory pathway. EBioMedicine 2019; 45: 495–510,
  48. Inoue T., Abe C., Kohro T., Tanaka S., Huang L., Yao J., Zheng S., Ye H., Inagi R., Stornetta R.L., Rosin D.L., Nangaku M., Wada Y., Okusa M.D. Non-canonical cholinergic anti-inflammatory pathway-mediated activation of peritoneal macrophages induces Hes1 and blocks ischemia/reperfusion injury in the kidney. Kidney Int 2019; 95(3): 563–576,
  49. Li Z., Hao H., Gao Y., Wang Z., Lu W., Liu J. Expression and localization analyses of the cholinergic anti-inflammatory pathway and α7nAchR in different tissues of rats with rheumatoid arthritis. Acta Histochem 2019; 121(6): 742–749,
  50. Yamada M., Ichinose M. The cholinergic pathways in inflammation: a potential pharmacotherapeutic target for COPD. Front Pharmacol 2018; 9: 1426,
  51. Tian Y., Miao B., Charles E.J., Wu D., Kron I.L., French B.A., Yang Z. Stimulation of the beta2 adrenergic receptor at reperfusion limits myocardial reperfusion injury via an interleukin-10-dependent anti-inflammatory pathway in the spleen. Circ J 2018; 82(11): 2829–2836,
  52. Antunes G.L., Silveira J.S., Kaiber D.B., Luft C., da Costa M.S., Marques E.P., Ferreira F.S., Breda R.V., Wyse A.T.S., Stein R.T., Pitrez P.M., da Cunha A.A. Cholinergic anti-inflammatory pathway confers airway protection against oxidative damage and attenuates inflammation in an allergic asthma model. J Cell Physiol 2020; 235(2): 1838–1849,
  53. Jarczyk J., Yard B.A., Hoeger S. The cholinergic anti-inflammatory pathway as a conceptual framework to treat inflammation-mediated renal injury. Kidney Blood Press Res 2019; 44(4): 435–448,
  54. Hajiasgharzadeh K., Baradaran B. Cholinergic anti-inflammatory pathway and the liver. Adv Pharm Bull 2017; 7(4): 507–513,
  55. Xu H., Shi Q., Mo Y., Wu L., Gu J., Xu Y. Downregulation of α7 nicotinic acetylcholine receptors in peripheral blood monocytes is associated with enhanced inflammation in preeclampsia. BMC Pregnancy Childbirth 2019; 19(1): 188,
  56. Fernández-Cabezudo M.J., George J.A., Bashir G., Mohamed Y.A., Al-Mansori A., Qureshi M.M., Lorke D.E., Petroianu G., Al-Ramadi B.K. Involvement of acetylcholine receptors in cholinergic pathway-mediated protection against autoimmune diabetes. Front Immunol 2019; 10: 1038,
  57. Gálvez I., Martín-Cordero L., Hinchado M.D., Álvarez-Barrientos A., Ortega E. Anti-inflammatory effect of β2 adrenergic stimulation on circulating monocytes with a pro-inflammatory state in high-fat diet-induced obesity. Brain Behav Immun 2019; 80: 564–572,
  58. Ortega E., Gálvez I., Martín-Cordero L. Adrenergic regulation of macrophage-mediated innate/inflammatory responses in obesity and exercise in this condition: role of β2 adrenergic receptors. Endocr Metab Immune Disord Drug Targets 2019; 19(8): 1089–1099,
  59. Hatakeyama N., Matsuda N. Alert cell strategy: mechanisms of inflammatory response and organ protection. Curr Pharm Des 2014; 20(36): 5766–5778,
  60. Clar D.T., Sharma S. Autonomic pharmacology. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019. URL:
  61. Samuel S., Allison T.A., Lee K., Choi H.A. Pharmacologic management of paroxysmal sympathetic hyperactivity after brain injury. J Neurosci Nurs 2016; 48(2): 82–89,
  62. Lehner K.R., Silverman H.A., Addorisio M.E., Roy A., Al-Onaizi M.A., Levine Y., Olofsson P.S., Chavan S.S., Gros R., Nathanson N.M., Al-Abed Y., Metz C.N., Prado V.F., Prado M.A.M., Tracey K.J., Pavlov V.A. Forebrain cholinergic signaling regulates innate immune responses and inflammation. Front Immunol 2019; 10: 585,
  63. Chang E.H., Chavan S.S., Pavlov V.A. Cholinergic control of inflammation, metabolic dysfunction, and cognitive impairment in obesity-associated disorders: mechanisms and novel therapeutic opportunities. Front Neurosci 2019; 13: 263,
  64. Njoku I., Radabaugh H.L., Nicholas M.A., Kutash L.A., O’Neil D.A., Marshall I.P., Cheng J.P., Kline A.E., Bondi C.O. Chronic treatment with galantamine rescues reversal learning in an attentional set-shifting test after experimental brain trauma. Exp Neurol 2019; 315: 32–41,
  65. Pinder N., Bruckner T., Lehmann M., Motsch J., Brenner T., Larmann J., Knebel P., Hoppe-Tichy T., Swoboda S., Weigand M.A., Hofer S., Zimmermann J.B. Effect of physostigmine on recovery from septic shock following intra-abdominal infection — results from a randomized, double-blind, placebo-controlled, monocentric pilot trial (Anticholium® per Se). J Crit Care 2019; 52: 126–135,
  66. Chen Y., Zhang X., Zhang B., He G., Zhou L., Xie Y. Dexmedetomidine reduces the neuronal apoptosis related to cardiopulmonary bypass by inhibiting activation of the JAK2-STAT3 pathway. Drug Des Devel Ther 2017; 11: 2787–2799,
  67. Xu K.L., Liu X.Q., Yao Y.L., Ye M.R., Han Y.G., Zhang T., Chen G., Lei M. Effect of dexmedetomidine on rats with convulsive status epilepticus and association with activation of cholinergic anti-inflammatory pathway. Biochem Biophys Res Commun 2018; 495(1): 421–426,
  68. Yamanaka D., Kawano T., Nishigaki A., Aoyama B., Tateiwa H., Shigematsu-Locatelli M., Locatelli F.M., Yokoyama M. Preventive effects of dexmedetomidine on the development of cognitive dysfunction following systemic inflammation in aged rats. J Anesth 2017; 31(1): 25–35,
  69. Cai Y., Xu H., Yan J., Zhang L., Lu Y. Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury. Mol Med Rep 2014; 9(5): 1542–1550,
  70. Zhang J., Xia F., Zhao H., Peng K., Liu H., Meng X., Chen C., Ji F. Dexmedetomidine-induced cardioprotection is mediated by inhibition of high mobility group box-1 and the cholinergic anti-inflammatory pathway in myocardial ischemia-reperfusion injury. PLoS One 2019; 14(7): e0218726,
  71. Jiang L., Hu M., Lu Y., Cao Y., Chang Y., Dai Z. The protective effects of dexmedetomidine on ischemic brain injury: a meta-analysis. J Clin Anesth 2017; 40: 25–32,
  72. Hu J., Vacas S., Feng X., Lutrin D., Uchida Y., Lai I.K., Maze M. Dexmedetomidine prevents cognitive decline by enhancing resolution of high mobility group box 1 protein-induced inflammation through a vagomimetic action in mice. Anesthesiology 2018; 128(5): 921–931,
  73. Janssen T.L., Alberts A.R., Hooft L., Mattace-Raso F., Mosk C.A., van der Laan L. Prevention of postoperative delirium in elderly patients planned for elective surgery: systematic review and meta-analysis. Clin Interv Aging 2019; 14: 1095–1117,
  74. Lankadeva Y.R., Ma S., Iguchi N., Evans R.G., Hood S.G., Farmer D.G.S., Bailey S.R., Bellomo R., May C.N. Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury. Kidney Int 2019; 96(5): 1150–1161,
  75. Zi S.F., Li J.H., Liu L., Deng C., Ao X., Chen D.D., Wu S.Z. Dexmedetomidine-mediated protection against septic liver injury depends on TLR4/MyD88/NF-κB signaling downregulation partly via cholinergic anti-inflammatory mechanisms. Int Immunopharmacol 2019; 76: 105898,
  76. Suzuki T., Suzuki Y., Okuda J., Kurazumi T., Suhara T., Ueda T., Nagata H., Morisaki H. Sepsis-induced cardiac dysfunction and β-adrenergic blockade therapy for sepsis. J Intensive Care 2017; 5: 22,
  77. Brown S.M., Beesley S.J., Lanspa M.J., Grissom C.K., Wilson E.L., Parikh S.M., Sarge T., Talmor D., Banner-Goodspeed V., Novack V., Thompson B.T., Shahul S.; Esmolol to Control Adrenergic Storm in Septic Shock-ROLL-IN (ECASSS-R) study. Esmolol infusion in patients with septic shock and tachycardia: a prospective, single-arm, feasibility study. Pilot Feasibility Study 2018; 4: 132,
  78. Breit S., Kupferberg A., Rogler G., Hasler G. Vagus nerve as modulator of the brain-gut axis in psychiatric and inflammatory disorders. Front Psychiatry 2018; 9: 44,
  79. Carod-Artal F.J. Infectious diseases causing autonomic dysfunction. Clin Auton Res 2017; 28(1): 67–81,
  80. Han C., Rice M.W., Cai D. Neuroinflammatory and autonomic mechanisms in diabetes and hypertension. Am J Physiol Endocrinol Metab 2016; 311(1): E32–E41,
  81. Gao H., Molinas A.J.R., Miyata K., Qiao X., Zsombok A. Overactivity of liver-related neurons in the paraventricular nucleus of the hypothalamus: electrophysiological findings in db/db mice. J Neurosci 2017; 37(46): 11140–11150,
  82. Hong G.S., Zillekens A., Schneiker B., Pantelis D., de Jonge W.J., Schaefer N., Kalff J.C., Wehner S. Non-invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice. Neurogastroenterol Motil 2019; 31(3): e13501,
  83. Bosmans G., Appeltans I., Stakenborg N., Gomez-Pinilla P.J., Florens M.V., Aguilera-Lizarraga J., Matteoli G., Boeckxstaens G.E. Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy. Allergy 2019; 74(9): 1748–1759,
  84. Papaioannou V., Pnevmatikos I. Heart rate variability: a potential tool for monitoring immunomodulatory effects of parenteral fish oil feeding in patients with sepsis. Nutr Metab Insights 2019; 12: 1178638819847486,
  85. Hoover В.B. Cholinergic modulation of the immune system presents new approaches for treating inflammation. Pharmacol Ther 2017; 179: 1–16,
  86. Tao G., Min-Hua C., Feng-Chan X., Yan C., Ting S., Wei-Qin L., Wen-Kui Y. Changes of plasma acetylcholine and inflammatory markers in critically ill patients during early enteral nutrition: a prospective observational study. J Crit Care 2019; 52: 219–226,
  87. Roewe J., Higer M., Riehl D.R., Gericke A., Radsak M.P., Bosmann M. Neuroendocrine modulation of IL-27 in macrophages. J Immunol 2017; 199(7): 2503–2514,
  88. Ağaç D., Estrada L.D., Maples R., Hooper L.V., Farrar J.D. The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion. Brain Behav Immun 2018; 74: 176–185,
  89. Li H.M., Li K.Y., Xing Y., Tang X.X., Yang D.M., Dai X.M., Lu D.X., Wang H.D. Phenylephrine attenuated sepsis-induced cardiac inflammation and mitochondrial injury through an effect on the PI3K/Akt signaling pathway. J Cardiovasc Pharmacol 2019; 73(3): 186–194,
  90. Mogilevski T., Burgell R., Aziz Q., Gibson P.R. Review article: the role of the autonomic nervous system in the pathogenesis and therapy of IBD. Aliment Pharmacol Ther 2019; 50(7): 720–737,
  91. Sonnenberg G.F., Hepworth M.R. Functional interactions between innate lymphoid cells and adaptive immunity. Nat Rev Immunol 2019; 19(10): 599–613,
  92. Serhan C.N., de la Rosa X., Jouvene C. Novel mediators and mechanisms in the resolution of infectious inflammation: evidence for vagus regulation. J Intern Med 2019; 286(3): 240–258,
  93. Carnagarin R., Matthews V., Zaldivia M.T.K., Schlaich M.P. The bidirectional interaction between the sympathetic nervous system and immune mechanisms in the pathogenesis of hypertension. Br J Pharmacol 2019; 176(12): 1839–1852,
  94. Reardon C. Neuro-immune interactions in the cholinergic anti-inflammatory reflex. Immunol Lett 2016; 178: 92–96,
  95. Eduardo C.-R.C., Alejandra T.-I.G., Guadalupe D.-R.K.J., Herminia V.-R.G., Lenin P., Enrique B.-V., Evandro B.M., Oscar B., Iván G.-P.M. Modulation of the extraneuronal cholinergic system on main innate response leukocytes. J Neuroimmunol 2019; 327: 22–35,
  96. Pereira M.R., Leite P.E. The involvement of parasympathetic and sympathetic nerve in the inflammatory reflex. J Cell Physiol 2016; 231(9): 1862–1869,
  97. Kim H.G., Cheon E.J., Bai D.S., Lee Y.H., Koo B.H. Stress and heart rate variability: a meta-analysis and review of the literature. Psychiatry Investig 2018; 15(3): 235–245,
  98. Liu L., Zhao M., Yu X., Zang W. Pharmacological modulation of vagal nerve activity in cardiovascular diseases. Neurosci Bull 2019; 35(1): 156–166,
  99. Crippa I.A., Subirà C., Vincent J.L., Fernandez R.F., Hernandez S.C., Cavicchi F.Z., Creteur J., Taccone F.S. Impaired cerebral autoregulation is associated with brain dysfunction in patients with sepsis. Crit Care 2018; 22(1): 327,
  100. Sanz D., D’Arco F., Robles C.A., Brierley J. Incidence and pattern of brain lesions in paediatric septic shock patients. Br J Radiol 2018; 91(1084): 20170861,
  101. Esen F., Orhun G., Özcan P.E., Brenes Bastos A.R., Tüzün E. Diagnosing acute brain dysfunction due to sepsis. Neurol Sci 2020; 41(1): 25–33,
  102. Günther A., Schubert J., Witte O.W., Brämer D. Intensive care aspects of autoimmune encephalitis. Med Klin Intensivmed Notfmed 2019; 14(7): 620–627,
  103. Bonjorno Junior J.C., Caruso F.R., Mendes R.G., da Silva T.R., Biazon T.M.P.C., Rangel F., Phillips S.A., Arena R., Borghi-Silva A. Noninvasive measurements of hemodynamic, autonomic and endothelial function as predictors of mortality in sepsis: a prospective cohort study. PLoS One 2019; 14(3): e0213239,
  104. Biteker F.S., Özlek B., Çelik O., Özlek E., Çil C., Doğan V., Biteker M. Autonomic imbalance in sepsis. Am J Emerg Med 2018; 36(2): 322,
  105. Tracey K.J. The inflammatory reflex. Nature 2002; 420(6917): 853–859,
Kiryachkov Y.Y., Bosenko S.A., Muslimov B.G., Petrova M.V. Dysfunction of the Autonomic Nervous System and Its Role in the Pathogenesis of Septic Critical Illness (Review). Sovremennye tehnologii v medicine 2020; 12(4): 106,

Journal in Databases