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Yearbook of Intensive Care and Emergency Medicine pp 141–150Cite as

Lymphocyte Apoptosis in Sepsis and Potential Anti-apoptotic Strategies

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Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 2009))

Abstract

Sepsis is a leading cause of death in many intensive care units [1]. The pathophysiology of sepsis is characterized by a dysregulation of the immune system in response to infection or secondary to trauma. Initial hyperinflammation often results in septic shock. Simultaneously, part of the immune system is deactivated leading to a temporary but often deadly immunosuppression. In attempting to arrive at a more detailed understanding of immunophysiological processes during sepsis over the last few years, apoptosis has been recognized as one of the key factors in the pathophysiology of sepsis [2]. As shown in several animal models, accelerated apoptosis seems to be induced in leukocytes and many immunocompetent cells during sepsis [3, 4]. Similar processes are involved in humans [5].

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References

  1. Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348: 138–150

    Article  PubMed  CAS  Google Scholar 

  2. Hotchkiss RS, Nicholson DW (2006) Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 6: 813–822

    Article  PubMed  CAS  Google Scholar 

  3. Ayala A, Herdon CD, Lehman DL, Ayala CA, Chaudry IH (1996) Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators. Blood 87: 4261–4275

    PubMed  CAS  Google Scholar 

  4. Wang SD, Huang KJ, Lin YS, Lei HY (1994) Sepsis-induced apoptosis of the thymocytes in mice. J Immunol 152: 5014–5021

    PubMed  CAS  Google Scholar 

  5. Hotchkiss RS, Swanson PE, Freeman BD, et al (1999) Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 27: 1230–1251

    Article  PubMed  CAS  Google Scholar 

  6. Wheeler AP, Bernard GR (1999) Treating patients with severe sepsis.N Engl J Med 340: 207–214

    Article  PubMed  CAS  Google Scholar 

  7. Kox WJ, Volk T, Kox SN, Volk HD (2000) Immunomodulatory therapies in sepsis. Intensive Care Med 26(Suppl 1):S124–S128

    Article  PubMed  Google Scholar 

  8. Hotchkiss RS, Chang KC, Swanson PE, et al (2000) Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat Immunol 1: 496–501

    Article  PubMed  CAS  Google Scholar 

  9. Fisher CJ,Jr., Agosti JM, Opal SM, et al (1996) Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med 334: 1697–1702

    Article  PubMed  CAS  Google Scholar 

  10. Weber SU, Brummer-Smith S, Schroeder S (2008) Apoptosis in sepsis. In: Fenton RH, Burnside CB (eds) Cell Apoptosis Research Progress, 1st edn. Nova Science Publishers Inc, Hauppauge, pp 113–134

    Google Scholar 

  11. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407: 770–776

    Article  PubMed  CAS  Google Scholar 

  12. Perl M, Chung CS, Ayala A (2005) Apoptosis. Crit Care Med 33: S526–S529

    Article  PubMed  Google Scholar 

  13. Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305: 626–629

    Article  PubMed  CAS  Google Scholar 

  14. Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11: 381–389

    Article  PubMed  CAS  Google Scholar 

  15. Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407: 789–795

    Article  PubMed  CAS  Google Scholar 

  16. Weber SU, Schewe JC, Putensen C, Stüber F, Schröder S (2004) [Apoptosis as a pathomechanism in sepsis]. Anaesthesist 53: 59–65

    Article  PubMed  CAS  Google Scholar 

  17. Zamzami N, Kroemer G (2001) The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2: 67–71

    Article  PubMed  CAS  Google Scholar 

  18. Braun JS, Novak R, Herzog KH, Bodner SM, Cleveland JL, Tuomanen EI (1999) Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat Med 5: 298–302

    Article  PubMed  CAS  Google Scholar 

  19. Hotchkiss RS, Tinsley KW, Swanson PE, et al (1999) Prevention of lymphocyte cell death in sepsis improves survival in mice. Proc Natl Acad Sci USA 96: 14541–14546

    Article  PubMed  CAS  Google Scholar 

  20. Neviere R, Fauvel H, Chopin C, Formstecher P, Marchetti P (2001) Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis. Am J Respir Crit Care Med 163: 218–225

    PubMed  CAS  Google Scholar 

  21. Hotchkiss RS, Coopersmith CM, Karl IE (2005) Prevention of lymphocyte apoptosis-a potential treatment of sepsis? Clin Infect Dis 41(Suppl 7):S465–S469

    Article  PubMed  CAS  Google Scholar 

  22. Rouquet N, Pages JC, Molina T, Briand P, Joulin V (1996) ICE inhibitor YVADcmk is a potent therapeutic agent against in vivo liver apoptosis. Curr Biol 6: 1192–1195

    Article  PubMed  CAS  Google Scholar 

  23. Wesche-Soldato DE, Swan RZ, Chung CS, Ayala A (2007) The apoptotic pathway as a therapeutic target in sepsis. Curr Drug Targets 8: 493–500

    Article  PubMed  CAS  Google Scholar 

  24. Kang SJ, Wang S, Kuida K, Yuan J (2002) Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response. Cell Death Differ 9: 1115–1125

    Article  PubMed  CAS  Google Scholar 

  25. Wesche-Soldato DE, Chung CS, Lomas-Neira J, Doughty LA, Gregory SH, Ayala A (2005) In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice. Blood 106: 2295–2301

    Article  PubMed  CAS  Google Scholar 

  26. Saleh M, Vaillancourt JP, Graham RK, et al (2004) Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature 429: 75–79

    Article  PubMed  CAS  Google Scholar 

  27. Ayala A, Chung CS, Xu YX, Evans TA, Redmond KM, Chaudry IH (1999) Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin. Immunology 97: 45–55

    Article  PubMed  CAS  Google Scholar 

  28. Chung CS, Yang S, Song GY, et al (2001) Inhibition of Fas signaling prevents hepatic injury and improves organ blood flow during sepsis. Surgery 130: 339–345

    Article  PubMed  CAS  Google Scholar 

  29. Hotchkiss RS, Swanson PE, Knudson CM, et al (1999) Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol 162: 4148–4156

    PubMed  CAS  Google Scholar 

  30. Hotchkiss RS, McConnell KW, Bullok K, et al (2006) TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte apoptosis in vivo. J Immunol 176: 5471–5477

    PubMed  CAS  Google Scholar 

  31. Bommhardt U, Chang KC, Swanson PE, et al (2004) Akt decreases lymphocyte apoptosis and improves survival in sepsis. J Immunol 172: 7583–7591

    PubMed  CAS  Google Scholar 

  32. Zeerleder S, Zwart B, Wuillemin WA, et al (2003) Elevated nucleosome levels in systemic inflammation and sepsis. Crit Care Med 31: 1947–1951

    Article  PubMed  CAS  Google Scholar 

  33. Bilbault P, Lavaux T, Lahlou A, et al (2004) Transient Bcl-2 gene down-expression in circulating mononuclear cells of severe sepsis patients who died despite appropriate intensive care. Intensive Care Med 30: 408–415

    Article  PubMed  Google Scholar 

  34. Hotchkiss RS, Tinsley KW, Swanson PE, et al (2001) Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 166: 6952–6963

    PubMed  CAS  Google Scholar 

  35. Hotchkiss RS, Tinsley KW, Swanson PE, et al (2002) Depletion of dendritic cells, but not macrophages, in patients with sepsis. J Immunol. 168: 2493–2500

    PubMed  CAS  Google Scholar 

  36. Schroeder S, Lindemann C, Decker D, et al (2001) Increased susceptibility to apoptosis in circulating lymphocytes of critically ill patients. Langenbecks Arch Surg. 386: 42–46

    Article  PubMed  CAS  Google Scholar 

  37. Roth G, Moser B, Krenn C, et al (2003) Susceptibility to programmed cell death in T-lymphocytes from septic patients: a mechanism for lymphopenia and Th2 predominance. Biochem Biophys Res Commun 308: 840–846

    Article  PubMed  CAS  Google Scholar 

  38. Adrie C, Bachelet M, Vayssier-Taussat M, et al (2001) Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis. Am J Respir Crit Care Med 164: 389–395

    PubMed  CAS  Google Scholar 

  39. Doughty L, Clark RS, Kaplan SS, Sasser H, Carcillo J (2002) sFas and sFas ligand and pediatric sepsis-induced multiple organ failure syndrome. Pediatr Res 52: 922–927

    PubMed  CAS  Google Scholar 

  40. Papathanassoglou ED, Moynihan JA, Vermillion DL, McDermott MP, Ackerman MH (2000) Soluble fas levels correlate with multiple organ dysfunction severity, survival and nitrate levels, but not with cellular apoptotic markers in critically ill patients. Shock 14: 107–112

    Article  PubMed  CAS  Google Scholar 

  41. Torre D, Tambini R, Manfredi M, et al (2003) Circulating levels of FAS/APO-1 in patients with the systemic inflammatory response syndrome. Diagn Microbiol Infect Dis 45: 233–236

    Article  PubMed  CAS  Google Scholar 

  42. De Freitas I, Fernandez-Somoza M, Essenfeld-Sekler E, Cardier JE (2004) Serum levels of the apoptosis-associated molecules, tumor necrosis factor-alpha/tumor necrosis factor type-I receptor and Fas/FasL, in sepsis. Chest 125: 2238–2246

    Article  PubMed  Google Scholar 

  43. Marsik C, Halama T, Cardona F, et al (2003) Regulation of Fas (APO-1, CD95) and Fas ligand expression in leukocytes during systemic inflammation in humans. Shock 20: 493–496

    Article  PubMed  CAS  Google Scholar 

  44. Papathanassoglou ED, Moynihan JA, McDermott MP, Ackerman MH(2001) Expression of Fas (CD95) and Fas ligand on peripheral blood mononuclear cells in critical illness and association with multiorgan dysfunction severity and survival. Crit Care Med 29: 709–718

    Article  PubMed  CAS  Google Scholar 

  45. Perfettini JL, Kroemer G(2003) Caspase activation is not death. Nat Immunol 4: 308–310

    Article  PubMed  CAS  Google Scholar 

  46. Cauwels A, Janssen B, Waeytens A, Cuvelier C, Brouckaert P (2003) Caspase inhibition causes hyperacute tumor necrosis factor-induced shock via oxidative stress and phospholipase A2. Nat Immunol 4: 387–393

    Article  PubMed  CAS  Google Scholar 

  47. Kroemer G, Martin SJ (2005) Caspase-independent cell death. Nat Med 11: 725–730

    Article  PubMed  Google Scholar 

  48. Weaver JG, Rouse MS, Steckelberg JM, Badley AD (2004) Improved survival in experimental sepsis with an orally administered inhibitor of apoptosis. Faseb J 18: 1185–1191

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care, University of Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany

    S. Weber & B. Baessler

  2. Department of Anesthesiology and Intensive Care, Westküstenklinikum Heide, Esmarchstrasse 50, 25746, Heide, Germany

    S. Schroeder

Authors
  1. S. Weber
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  2. B. Baessler
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  3. S. Schroeder
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Editors and Affiliations

  1. Department of Intensive Care Erasme Hospital, Université libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Head) (Head)

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Weber, S., Baessler, B., Schroeder, S. (2009). Lymphocyte Apoptosis in Sepsis and Potential Anti-apoptotic Strategies. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine. Yearbook of Intensive Care and Emergency Medicine, vol 2009. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-92276-6_14

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  • DOI: https://doi.org/10.1007/978-3-540-92276-6_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-92275-9

  • Online ISBN: 978-3-540-92276-6

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