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VOLUME 17 , ISSUE 3 ( June, 2013 ) > List of Articles

REVIEW ARTICLE

Sepsis induced immunosuppression: Implications for secondary infections and complications

Krishna M. Sundar, Mazen Sires

Keywords : Chronic critical care illness, sepsis, immune dysfunction, pneumonia, ventilator-associated

Citation Information : Sundar KM, Sires M. Sepsis induced immunosuppression: Implications for secondary infections and complications. Indian J Crit Care Med 2013; 17 (3):162-169.

DOI: 10.4103/0972-5229.117054

License: CC BY-ND 3.0

Published Online: 01-06-2014

Copyright Statement:  Copyright © 2013; The Author(s).


Abstract

Sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis. This review explores the basis for sepsis related immune dysfunction and discusses its clinical implications for the treating intensivist. Recent trends indicate that a significant proportion of septic patients succumb to the complications of secondary infections and chronic critical care illness from the initial bout of sepsis. Therefore care-givers in the ICU need to be aware of the impediments posed by sepsis-related immune dysfunction that can impair recovery in patients with sepsis and contribute to sepsis-related mortality.

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  1. Skrupky LP, Kerby PW, Hotchkiss RS. Advances in the management of sepsis and the understanding of key immunologic defects. Anesthesiology 2011;115:1349-62.
  2. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.
  3. Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest 1992;101:1481-3.
  4. Bone RC. 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 1996;125:680-7.
  5. van der Poll T, Meijers JC. Systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome in sepsis. J Innate Immun 2010;2:379-80.
  6. Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA. The sepsis seesaw: Tilting toward immunosuppression. Nat Med 2009;15:496-7.
  7. Chong DL, Sriskandan S. Pro-inflammatory mechanisms in sepsis. Contrib Microbiol 2011;17:86-107.
  8. De Gaudio AR, Rinaldi S, Chelazzi C, Borracci T. Pathophysiology of sepsis in the elderly: Clinical impact and therapeutic considerations. Curr Drug Targets 2009;10:60-70.
  9. Jean-Baptiste E. Cellular mechanisms in sepsis. J Intensive Care Med 2007;22:63-72.
  10. McCall CE, El Gazzar M, Liu T, Vachharajani V, Yoza B. Epigenetics, bioenergetics, and microRNA coordinate gene-specific reprogramming during acute systemic inflammation. J Leukoc Biol 2011;90:439-46.
  11. McCall CE, Yoza BK. Gene silencing in severe systemic inflammation. Am J Respir Crit Care Med 2007;175:763-7.
  12. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138-50.
  13. Heidecke CD, Hensler T, Weighardt H, Zantl N, Wagner H, Siewert JR, et al. Selective defects of T lymphocyte function in patients with lethal intraabdominal infection. Am J Surg 1999;178:288-92.
  14. Tinsley KW, Grayson MH, Swanson PE, Drewry AM, Chang KC, Karl IE, et al. Sepsis induces apoptosis and profound depletion of splenic interdigitating and follicular dendritic cells. J Immunol 2003;171:909-14.
  15. Sáenz JJ, Izura JJ, Manrique A, Sala F, Gaminde I. Early prognosis in severe sepsis via analyzing the monocyte immunophenotype. Intensive Care Med 2001;27:970-7.
  16. Volk HD, Reinke P, Döcke WD. Clinical aspects: From systemic inflammation to ′immunoparalysis′. Chem Immunol 2000;74:162-77.
  17. Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+T cell activation during HIV infection. Nat Med 2010;16:452-9.
  18. Hotchkiss RS, Opal S. Immunotherapy for sepsis: A new approach against an ancient foe. N Engl J Med 2010;363:87-9.
  19. Bantel H, Schulze-Osthoff K. Cell death in sepsis: A matter of how, when, and where. Crit Care 2009;13:173.
  20. Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 1999;27:1230-51.
  21. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med 2009;361:1570-83.
  22. Chang KC, Unsinger J, Davis CG, Schwulst SJ, Muenzer JT, Strasser A, et al. Multiple triggers of cell death in sepsis: Death receptor and mitochondrial-Mediated apoptosis. FASEB J 2007;21:708-19.
  23. Hofer S, Brenner T, Bopp C, Steppan J, Lichtenstern C, Weitz J, et al. Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction. Crit Care 2009;13:R93.
  24. Giamarellos-Bourboulis EJ, Routsi C, Plachouras D, Markaki V, Raftogiannis M, Zervakis D, et al. Early apoptosis of blood monocytes in the septic host: Is it a mechanism of protection in the event of septic shock? Crit Care 2006;10:R76.
  25. Gogos C, Kotsaki A, Pelekanou A, Giannikopoulos G, Vaki I, Maravitsa P, et al. Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection. Crit Care 2010;14:R96.
  26. Turnbull IR, Clark AT, Stromberg PE, Dixon DJ, Woolsey CA, Davis CG, et al. Effects of aging on the immunopathologic response to sepsis. Crit Care Med 2009;37:1018-23.
  27. Rosolem MM, Rabello LS, Lisboa T, Caruso P, Costa RT, Leal JV, et al. Critically ill patients with cancer and sepsis: Clinical course and prognostic factors. J Crit Care 2012;27:301-7.
  28. Pierrakos C, Vincent JL. Sepsis biomarkers: A review. Crit Care 2010;14:R15.
  29. Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005;41 Suppl 7:S504-12.
  30. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-10.
  31. Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: A systematic review. Crit Care Med 2005;33:2184-93.
  32. Morrow LE, Kollef MH. Recognition and prevention of nosocomial pneumonia in the intensive care unit and infection control in mechanical ventilation. Crit Care Med 2010;38:S352-62.
  33. Chastre J. Conference summary: Ventilator-associated pneumonia. Respir Care 2005;50:975-83.
  34. Pelekanou A, Tsangaris I, Kotsaki A, Karagianni V, Giamarellou H, Armaganidis A, et al. Decrease of CD4-lymphocytes and apoptosis of CD14-monocytes are characteristic alterations in sepsis caused by ventilator-associated pneumonia: Results from an observational study. Crit Care 2009;13:R172.
  35. Ramírez P, Ferrer M, Gimeno R, Tormo S, Valencia M, Piñer R, et al. Systemic inflammatory response and increased risk for ventilator-associated pneumonia: A preliminary study. Crit Care Med 2009;37:1691-5.
  36. Hall MW, Knatz NL, Vetterly C, Tomarello S, Wewers MD, Volk HD, et al. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med 2011;37:525-32.
  37. Döcke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, et al. Monocyte deactivation in septic patients: Restoration by IFN-gamma treatment. Nat Med 1997;3:678-81.
  38. Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, et al. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 2008;300:413-22.
  39. Sundar KM, Ludwig KA, Alward WT, Pearce MJ, Bishop CT, Hammond RC, et al. Clinical course and spectrum of intensive care unit patients reactivating herpes simplex-1 virus: A retrospective analysis. Indian J Crit Care Med 2008;12:145-52.
  40. Osawa R, Singh N. Cytomegalovirus infection in critically ill patients: A systematic review. Crit Care 2009;13:R68.
  41. Simoons-Smit AM, Kraan EM, Beishuizen A, Strack van Schijndel RJ, Vandenbroucke-Grauls CM. Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander? Clin Microbiol Infect 2006;12:1050-9.
  42. Chiche L, Forel JM, Roch A, Guervilly C, Pauly V, Allardet-Servent J, et al. Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med 2009;37:1850-7.
  43. Luyt CE, Combes A, Deback C, Aubriot-Lorton MH, Nieszkowska A, Trouillet JL, et al. Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation. Am J Respir Crit Care Med 2007;175:935-42.
  44. Cook CH, Trgovcich J. Cytomegalovirus reactivation in critically ill immunocompetent hosts: A decade of progress and remaining challenges. Antiviral Res 2011;90:151-9.
  45. Prellner T, Flamholc L, Haidl S, Lindholm K, Widell A. Herpes simplex virus: The most frequently isolated pathogen in the lungs of patients with severe respiratory distress. Scand J Infect Dis 1992;24:283-92.
  46. Cook CH, Martin LC, Yenchar JK, Lahm MC, McGuinness B, Davies EA, et al. Occult herpes family viral infections are endemic in critically ill surgical patients. Crit Care Med 2003;31:1923-9.
  47. Xie GH, Fang XM, Fang Q, Wu XM, Jin YH, Wang JL, et al. Impact of invasive fungal infection on outcomes of severe sepsis: A multicenter matched cohort study in critically ill surgical patients. Crit Care 2008;12:R5.
  48. Shoham S, Marwaha S. Invasive fungal infections in the ICU. J Intensive Care Med 2010;25:78-92.
  49. Playford EG, Marriott D, Nguyen Q, Chen S, Ellis D, Slavin M, et al. Candidemia in nonneutropenic critically ill patients: Risk factors for non-albicans Candida spp. Crit Care Med 2008;36:2034-9.
  50. Rosentul DC, Plantinga TS, Oosting M, Scott WK, Velez Edwards DR, Smith PB, et al. Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J Infect Dis 2011;204:1138-45.
  51. Rosentul DC, Plantinga TS, Scott WK, Alexander BD, van de Geer NM, Perfect JR, et al. The impact of caspase-12 on susceptibility to candidemia. Eur J Clin Microbiol Infect Dis 2012;31:277-80.
  52. Davis CG, Chang K, Osborne D, Walton AH, Dunne WM, Muenzer JT. Increased susceptibility to Candida infection following cecal ligation and puncture. Biochem Biophys Res Commun 2011;414:37-43.
  53. Freeman BD, Natanson C. Anti-inflammatory therapies in sepsis and septic shock. Expert Opin Investig Drugs 2000;9:1651-63.
  54. Inoue S, Unsinger J, Davis CG, Muenzer JT, Ferguson TA, Chang K, et al. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis. J Immunol 2010;184:1401-9.
  55. Hotchkiss RS, McConnell KW, Bullok K, Davis CG, Chang KC, Schwulst SJ, et al. TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte apoptosis in vivo. J Immunol 2006;176:5471-7.
  56. Hotchkiss RS, Coopersmith CM, Karl IE. Prevention of lymphocyte apoptosis: A potential treatment of sepsis? Clin Infect Dis 2005;41 Suppl 7:S465-9.
  57. Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 2011;306:2594-605.
  58. Kalechman Y, Gafter U, Gal R, Rushkin G, Yan D, Albeck M, et al. Anti-IL-10 therapeutic strategy using the immunomodulator AS101 in protecting mice from sepsis-induced death: Dependence on timing of immunomodulating intervention. J Immunol 2002;169:384-92.
  59. Muenzer JT, Davis CG, Chang K, Schmidt RE, Dunne WM, Coopersmith CM, et al. Characterization and modulation of the immunosuppressive phase of sepsis. Infect Immun 2010;78:1582-92.
  60. Wisnoski N, Chung CS, Chen Y, Huang X, Ayala A. The contribution of CD4+CD25+T-regulatory-cells to immune suppression in sepsis. Shock 2007;27:251-7.
  61. Inoue S, Bo L, Bian J, Unsinger J, Chang K, Hotchkiss RS. Dose-dependent effect of anti-CTLA-4 on survival in sepsis. Shock 2011;36:38-44.
  62. Brahmamdam P, Inoue S, Unsinger J, Chang KC, McDunn JE, Hotchkiss RS. Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol 2010;88:233-40.
  63. Marshall JC. Clinical trials of mediator-directed therapy in sepsis: What have we learned? Intensive Care Med 2000;26 Suppl 1:S75-83.
  64. Caldwell CC, Hotchkiss RS. The first step in utilizing immune-modulating therapies: Immune status determination. Crit Care 2011;15:108.
  65. Bo L, Wang F, Zhu J, Li J, Deng X. Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: A meta-analysis. Crit Care 2011;15:R58.
  66. Mohammad RA. Use of granulocyte colony-stimulating factor in patients with severe sepsis or septic shock. Am J Health Syst Pharm 2010;67:1238-45.
  67. Leentjens J, Kox M, Koch RM, Preijers F, Joosten LA, van der Hoeven JG, et al. Reversal of Immunoparalysis in Humans in vivo: A Double-blind Placebo-controlled Randomized Pilot-Study. Am J Respir Crit Care Med 2012.
  68. Mera S, Tatulescu D, Cismaru C, Bondor C, Slavcovici A, Zanc V, et al. Multiplex cytokine profiling in patients with sepsis. APMIS 2011;119:155-63.
  69. Flohé S, Lendemans S, Selbach C, Waydhas C, Ackermann M, Schade FU, et al. Effect of granulocyte-macrophage colony-stimulating factor on the immune response of circulating monocytes after severe trauma. Crit Care Med 2003;31:2462-9.
  70. Otto GP, Sossdorf M, Claus RA, Rödel J, Menge K, Reinhart K, et al. The late phase of sepsis is characterized by an increased microbiological burden and death rate. Crit Care 2011;15:R183.
  71. Nelson JE, Cox CE, Hope AA, Carson SS. Chronic critical illness. Am J Respir Crit Care Med 2010;182:446-54.
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