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Intensive Care Medicine pp 208–216Cite as

Immunomodulatory Effects of General Anesthetics

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Abstract

Postoperative patients are prone to develop infectious complications, and the phenomenon of immunoparalysis, defined as a diminished capacity of immunocompetent cells to respond to infectious agents, has been implicated as a major contributing factor. When inflammatory postoperative disorders are already established, intervention is difficult. However, if perioperative modulation of the inflammatory response were possible, this may influence postoperative outcome. General anesthetics exert a variety of effects, including sedation, amnesia, and analgesia. Current research focuses primarily on the effects of these compounds on membrane proteins in the central nervous system (CNS), to elucidate the molecular mechanism of their action. The (side-) effects of general anesthetics on other organ systems have been less extensively investigated. In this chapter, we will discuss the data available on the immunomodulatory effects of general anesthetics and the potential clinical implications of these effects on the development of (postoperative) infections.

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References

  1. Hollmann MW, Durieux ME (2000) Local anesthetics and the inflammatory response. Anesthesiology 93:858–875

    Article  PubMed  CAS  Google Scholar 

  2. Kirkland KB, Briggs JP, Trivett SL, Wilkinson WE, Sexton DJ (1999) The impact of surgical-site infections in the 1990s: Attributable mortality, excess length of hospitalization and extra costs. Infect Control Hosp Epidemiol 20:725–730

    Article  PubMed  CAS  Google Scholar 

  3. Bone RC (1996) Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Ann Intern Med 125:680–687

    PubMed  CAS  Google Scholar 

  4. Volk H (2002) Immunodepression in the surgical patient and increased susceptibility to infection. Crit Care 6:279–281

    Article  PubMed  Google Scholar 

  5. Ertel W, Kremer JP, Kenney J, et al (1995) Downregulation of proinflammatory cytokine release in whole blood from septic patients. Blood 85:1341–1347

    PubMed  CAS  Google Scholar 

  6. Lemaire LC, Van der Poll T, Van Lanschot JJ, et al (1998) Minimally invasive surgery induces endotoxin-tolerance in the absence of detectable endotoxemia. J Clin Immunol 18:414–420

    Article  PubMed  CAS  Google Scholar 

  7. Hensler T, Hecker H, Heeg K, et al (1997) Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun 65:2283–2291

    PubMed  CAS  Google Scholar 

  8. Munford RS, Pugin J (2001) Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med 163:316–321

    PubMed  CAS  Google Scholar 

  9. Döcke WD, Randow F, Sybre U, et al (1997) Monocyte deactivation in septic patients: Restoration by IFN-gamma treatment. Nat Med 3:678–681

    Article  PubMed  Google Scholar 

  10. Randow F, Sybre U, Meisel C, et al (1995). Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. J Exp Med 181:887–1892

    Article  Google Scholar 

  11. Wolk K, Döcke WD, Von Baehr V, Volk HD, Sabat R (2000) Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 96:218–223

    PubMed  CAS  Google Scholar 

  12. Lyons A, Kelly J, Rodrick M, J, Lederer J (1997) Major injury induces increased production of interleukin-10 by cells of the immune system with a negative impact on resistance to infection. Ann Surg 226:450–460

    Article  PubMed  CAS  Google Scholar 

  13. Wiersinga WJ, Van der Poll T (2006) The role of toll-like receptors in sepsis. In: Vincent JL (ed) Yearbook of Intensive Care and Emergency Medicine, 1st edn. Springer-Verlag, Berlin, pp 3–14

    Google Scholar 

  14. Jiang Q, Akashi S, Miyake K, Petty HR (2000) Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B. J Immunol 165:3541–3544

    PubMed  CAS  Google Scholar 

  15. Li S, Strelow A, Fontana EJ, Wesche H (2002) IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase. Proc Nat Acad Sci 99:5567–5572

    Article  PubMed  CAS  Google Scholar 

  16. Ono K, Han J (2000) The p38 signal transduction pathway: activation and function. Cell Signal 12:1–13

    Article  PubMed  CAS  Google Scholar 

  17. Nomura F, Akashi S, Sakao Y, et al (2000) Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression. J Immunol 164:3476–3479

    PubMed  CAS  Google Scholar 

  18. Hu J, Jacinto R, McCall C, Li L (2002) Regulation of IL-1 receptor-associated kinases by lipopolysaccharide. J Immunol 168:3910–3914

    PubMed  CAS  Google Scholar 

  19. Li L, Cousart S, Hu J, McCall C (2000) Characterization of interleukin-1 receptor associated kinase in normal and endotoxin-tolerant cells. J Biol Chem 275:23340–23345

    Article  PubMed  CAS  Google Scholar 

  20. Noubir S, Hmama Z, Reiner NE (2004) Dual receptors and distinct pathways mediate interleukin-1 receptor associated kinase degradation in response to lipopolysaccharide. J Biol Chem 279:25189–25195

    Article  PubMed  CAS  Google Scholar 

  21. Medvedev AE, Lentschat A, Wahl LM, Golenbock DT, Vogel SN (2002) Dysregulation of LPS-induced toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells. J Immunol 169:5209–5216

    PubMed  Google Scholar 

  22. Escoll P, Del Fresno C, Garcia L, et al (2003) Rapid up-regulation of IRAK-M expression following a second endotoxin challenge in human monocytes and in monocytes isolated from septic patients. Biochem Biophys Res Commun 311:465–472

    Article  PubMed  CAS  Google Scholar 

  23. Giraud O, Molliex S, Rolland C, et al (2003) Halogenated anesthetics reduce interleukin-1beta-induced cytokine secretion by rat alveolar type II cells in primary culture. Anesthesiology 98:74–81

    Article  PubMed  CAS  Google Scholar 

  24. Song HK, Jeong DC (2004) The effect of propofol on cytotoxicity and apoptosis of lipopoly-saccharide-treated mononuclear cells and lymphocytes. Anesth Analg 98:1724–1728

    Article  PubMed  CAS  Google Scholar 

  25. Takaono M, Yogosawa T, Okawa-Takatsuji M, Aotsuka S (2002) Effects of intravenous anesthetics on interleukin (IL)-6 and IL-10 production by lipopolysaccharide-stimulated mononuclear cells from healthy volunteers. Acta Anaesthesiol Scand 46:176–179

    Article  PubMed  CAS  Google Scholar 

  26. Gilliland HE, Armstrong M, Carabine U, McMurry T (1997) The choice of anesthetic maintenance technique influences the antiinflammatory cytokine response to abdominal surgery. Anesth Analg 85:1394–1398

    Article  PubMed  CAS  Google Scholar 

  27. Kotani N, Hashimoto H, Sessler D, et al (1998) Intraoperative modulation of alveolar macrophage function during isoflurane and propofol anesthesia. Anesthesiology 89:1125–1132

    Article  PubMed  CAS  Google Scholar 

  28. Kotani N, Hashimoto H, Sessler D, et al (1999) Expression of genes for proinflammatory cytokines in alveolar macrophages during propofol and isoflurane anesthesia. Anesth Analg 89:1250–1256

    Article  PubMed  CAS  Google Scholar 

  29. Kotani N, Takahashi S, Sessler D, et al (1999) Volatile anesthetics augment expression of proinflammatory cytokines in rat alveolar macrophages during mechanical ventilation. Anesthesiology 91:187–197

    Article  PubMed  CAS  Google Scholar 

  30. Taniguchi T, Yamamoto K, Ohmoto N, Ohta K, Kobayashi T (2000) Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats. Crit Care Med 28:1101–1106

    Article  PubMed  CAS  Google Scholar 

  31. Taniguchi T, Kanakura H, Yamamoto K (2002) Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats. Crit Care Med 30:904–907

    Article  PubMed  CAS  Google Scholar 

  32. Van Sandick JW, Gisbertz SS, Ten Berge I, et al (2003) Immune responses and prediction of major infection in patients undergoing transhiatal or transthoracic esophagectomy for cancer. Ann Surg 237:35–43

    Article  PubMed  Google Scholar 

  33. Chen RM, Wu CH, Chang HC, et al (2003) Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis. Anesthesiology 98:1178–1185

    Article  PubMed  CAS  Google Scholar 

  34. Larsen B, Hoff G, Wilhelm W, Buchinger H, Wanner G, Bauer M (1998) Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood. Anesthesiology 89:1218–1227

    Article  PubMed  CAS  Google Scholar 

  35. Franks NP, Lieb WR (1994) Molecular and cellular mechanisms of general anaesthesia. Nature 367:607–614

    Article  PubMed  CAS  Google Scholar 

  36. De Rossi LW, Brueckmann M, Rex S, Barderschneider M, Buhre W, Rossaint R (2004) Xenon and isoflurane differentially modulate lipopolysaccharide-induced activation of the nuclear transcription factor KB and production of tumor necrosis factor-α and interleukin-6 in monocytes. Anesth Analg 98:1007–1012

    Article  PubMed  Google Scholar 

  37. Loop T, Scheiermann P, Doviakue D, et al (2004) Sevoflurane inhibits phorbol-myristate-acetate induced activator protein-1 activation in human T lymphocytes in vitro: potential role of the p38-stress kinase pathway. Anesthesiology 101:710–721.

    Article  PubMed  CAS  Google Scholar 

  38. Mobert J, Zahler S, Becker B, Conzen P (1999) Inhibition of neutrophil activation by volatile anesthetics decreases adhesion to cultured human endothelial cells. Anesthesiology 90:1371–1381

    Article  Google Scholar 

  39. Reutershan J, Chang D, Hayes JK, Ley K (2006) Protective effects of isoflurane pretreatment in endotoxin-induced lung injury. Anesthesiology 104:511–517

    Article  PubMed  CAS  Google Scholar 

  40. Fuentes JM, Talamini MA, Fulton WB, Hanly EJ, Aurora AR, De Maio A (2006) General anesthesia delays the inflammatory response and increases survival for mice with endotoxic shock. Clin Vacc Immunol 13:281–288

    Article  CAS  Google Scholar 

  41. Heine J, Jaeger K, Osthaus A, et al (2000) Anaesthesia with propofol decreases FMLP-induced neutrophil respiratory burst but not phagocytosis compared with isoflurane. Br J Anaesth 85:424–430

    PubMed  CAS  Google Scholar 

  42. Wang H, Liao H, Ochani M, et al (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nature Med 10:1216–1221

    Article  PubMed  CAS  Google Scholar 

  43. Borovikova L, Ivanova S, Zhang M, et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462

    Article  PubMed  CAS  Google Scholar 

  44. Czura C, Tracey K (2005) Autonomic neuronal regulation of immunity. J Intern Med 257: 156–166

    Article  PubMed  CAS  Google Scholar 

  45. Irnaten M, Wang J, Venkatesan P (2002) Ketamine inhibits presynaptic and postsynaptic nicotinic excitation of identified cardiac parasympathetic neurons in nucleus ambiguus. Anesthesiology 96:667–674

    Article  PubMed  CAS  Google Scholar 

  46. Flood P, Ramirez-Latorre J, Role L (1997) Alpha4beta2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha-7 type nicotinic acetylcholine receptors are unaffected. Anesthesiology 86:859–865

    Article  PubMed  CAS  Google Scholar 

  47. Mazar J, Rogachev B, Shaked G, et al (2005) Involvement of adenosine in the anti-inflammatory action of ketamine. Anesthesiology 102:1174–1181

    Article  PubMed  CAS  Google Scholar 

  48. Bartoc C, Frumento RJ, Jalbout M, Bennett-Guerrero E, Du E, Nishanian E (2006) A randomized, double blind, placebo-controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients. J Cardiothorac Vasc Anesth 20:217–222

    Article  PubMed  CAS  Google Scholar 

  49. Hemmings HC, Adamo AI, Hoffman MM (1995) Biochemical characterization of the stimulatory effects of halothane and propofol on purified brain protein kinase C. Anesth Analg 81:1216–1222

    Article  PubMed  CAS  Google Scholar 

  50. Itoh T, Hirota K, Hisano T, Namba T, Fukuda K (2004) The volatile anesthetics halothane and isoflurane differentially modulate proinflammatory cytokine-induced p38 mitogen-activated protein kinase activation. J Anesth 18:203–209

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Anesthesiology, University Hospital, Heidelberglaan 100 Room Q4.2.313, 3584 CX, Utrecht, Netherlands

    L. C. Lemaire

  2. Center of Infection and Immunity and Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9 Room G2-130, 1105 AZ, Amsterdam, Netherlands

    T. van der Poll

Authors
  1. L. C. Lemaire
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  2. T. van der Poll
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Editor information

Editors and Affiliations

  1. Department of Intensive Care Erasme Hospital, Free University of Brussels, Route de Lennik 808, 1070, Brussels, Belgium

    Jean-Louis Vincent MD, PhD, FCCM, FCCP (Head) (Head)

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© 2007 Springer Science + Business Media Inc.

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Lemaire, L.C., van der Poll, T. (2007). Immunomodulatory Effects of General Anesthetics. In: Vincent, JL. (eds) Intensive Care Medicine. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49518-7_19

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  • DOI: https://doi.org/10.1007/978-0-387-49518-7_19

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-49517-0

  • Online ISBN: 978-0-387-49518-7

  • eBook Packages: MedicineMedicine (R0)

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