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Immune Monitoring and Strategies for Immune Modulation

  • Chapter
Immunology and Infectious Disease

Part of the book series: Molecular and Cellular Biology of Critical Care Medicine ((MCCM,volume 3))

Abstract

Antimicrobial defense against pathogens plays a key role in the protection of the body’s integrity. The first level of defense is based on relatively static physical and biological natural barriers e.g. mucosa, skin, pH, natural intestinal and vaginal flora. If the pathogens or their toxins penetrate these barriers, the inducible acute inflammatory system consisting of humoral factors (e.g. complement, type I interferons, defensins, proteolytic enzymes, cytokines) and inflammatory cells (e.g. mast cells, macrophages) located at body surfaces (skin, intestine, respiratory tract) react within minutes to hours. The resulting acute local inflammation exhibits strong antimicrobial properties. This response is also important for tissue regeneration and wound healing explaining the observation that inflammation is activated following sterile tissue injury (trauma, hypoxia). In addition, local inflammation activates the endothelium amplifying and attracting further humoral and cellular components (e.g. platelets, granulocytes, NK cells). Endothelial cells play an important role in induction of this secondary phase of acute inflammation. Normally, they form a barrier between the components of the blood circulation and tissue that can be passed by gases and low molecular weight substances only. Resting endothelial cells express anti-coagulant molecules like thrombomodulin at their surface to prevent coagulation.

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References

  1. Natanson C, Hoffmann WD, Suffredini AF et al. Selected treatment strategies for septic shock base don proposed mechanisms of pathogenesis. Ann Intern Med 1994; 120:771–783

    PubMed  CAS  Google Scholar 

  2. Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 1997; 25: 1095–1100

    Article  PubMed  CAS  Google Scholar 

  3. Volk HD, Reinke P, Doecke WD. Clinical aspects: from systemic inflammation to ‘immunoparalysis’ Chem Immunol 2000, 74: 162–177

    Article  PubMed  CAS  Google Scholar 

  4. Volk HD, Reinke P, Falck P et al. Diagnostic value of an immune monitoring program for the clinical management of immunosuppressed patients with septic complications. Clin Transplant 1989; 3: 246–252

    Google Scholar 

  5. Doecke WD, Randow F, Syrbe U et al. Monocyte deactivation in septic patients: restoration by IFNg treatment. Nat Med 1997; 3: 678–681

    Article  Google Scholar 

  6. Volk HD, Reinke P, Doecke WD. Immunological monitoring of th einflammatory process: which variables ? when to assess ? Eur J Surg Suppl 1999; 584: 70–72

    Article  PubMed  Google Scholar 

  7. Payen D, Faivre V, Lukaszewicz AC, Losser MR. Assessment of immunological status in th ecritically ill. Minerva Anestesiol 2000; 66: 757–763

    PubMed  CAS  Google Scholar 

  8. Krueger M, Nauck MS, Sang S et al. Cord blood levels of IL-6 and IL-8 for the immediate diagnosis of early-onset infection in premature infants. Biol Neonate 2001; 80:118–123

    Article  PubMed  CAS  Google Scholar 

  9. Dollner H, Vatten L, Linnebo I et al. Inflammatory mediators in umbilical plasma from neonates who develop early-onset sepsis. Biol Neonate 2001; 80: 41–47

    PubMed  CAS  Google Scholar 

  10. Berner R, Tuxen B, Clad A et al. Elevated gene expression of IL-8 in cord blood is a sensitive marker for neonatal infection. Eur J Pediatr 2000; 159: 205–210

    Article  PubMed  CAS  Google Scholar 

  11. Selberg O, Hecker H, Martin M et al. Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6. Crit Care Med 2000; 28: 2793–2798

    Article  PubMed  CAS  Google Scholar 

  12. Takala A, Jousela I, Jansson SE et al. Markers of systemic inflammation predicting organ failure in community-acquired septic shock. Clin Sci (Lond) 1999; 97: 529–538

    Article  CAS  Google Scholar 

  13. Dollner H, Vatten I, Austgulen R. Early diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6, soluble tumor necrosis factor receptors and soluble adhesion molecules. J Clin Epidemiol 2001; 54: 1251–1257

    Article  PubMed  CAS  Google Scholar 

  14. Ugarte H, Silva E, Mercan D et al. Procalcitonin used as a marker of infection in the intensive care unit. Crit Care Med 1999; 27: 498–504

    Article  PubMed  CAS  Google Scholar 

  15. Povoa P, Almeida E, Moreira P et al. C-reactive protein as an indicator of sepsis. Intensive Care Med 1998; 24: 1052–1056

    Article  PubMed  CAS  Google Scholar 

  16. Rothenburger M, Markewitz A, Lenz T et al. Detection of acute phase response and infection, the role of procalcitonin and C-reactive protein. Clin Chem Lab Med 1999; 37: 275–279

    Article  PubMed  CAS  Google Scholar 

  17. Sablotzki A, Borgermann J, Baulig W et al. Lipopolysaccaride-binding protein (LBP) and markers of acute-phase response in patients with multiple organ dysfunction syndrome (MODS) following open heart surgery. Thorac Cardiovasc Surg 2001; 49: 273–278

    Article  PubMed  CAS  Google Scholar 

  18. Asadullah K, Doecke WD, Reinke P et al. Cytokine determination, diagnostic significance from the clinical and immunological viewpoint. Dtsch Med Wochenschr 1997; 122: 1424–1431

    Article  PubMed  CAS  Google Scholar 

  19. Giannoudis PV, Smith RM, Perry SL et al. Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis. Intensive Care Med 2000; 26: 1076–1081

    Article  PubMed  CAS  Google Scholar 

  20. Taniguchi T, koido Y, Aiboshi J et al. Change in the ratio of IL-6 to IL-10 predicts poor outcome in patients with systemic inflammatory response syndrome. Crit Care Med 1999; 27: 1262–1264

    Article  PubMed  CAS  Google Scholar 

  21. Rodriguez-Gaspar M, Santolaria F, Jarque-Lopez A et al. Prognostic value of cytokines in SIRS general medical patients. Cytokine 2001; 15: 232–236

    Article  PubMed  CAS  Google Scholar 

  22. Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis an dfuture therapeutic options. J Infect dis 2000; 181: 176–180

    Article  PubMed  CAS  Google Scholar 

  23. Doughty L, Carcillo JA, Kaplan S, Janosky J. The compensatory anti-inflammatory cytokine IL-10 response in pediatric sepsis-induced multiple organ failure. Chest 1998; 113: 1625–1631

    Article  PubMed  CAS  Google Scholar 

  24. Hasper D, Hummel M, Kleber FX et al. Systemic inflammation in patients with heart failure. Eur Heart J 1998; 19: 681–682

    Article  Google Scholar 

  25. Niebauer J, Volk HD, Kemp M et al. Endotoxin an dimmune activation in chronic heart failure: a prospective cohort study. Lancet 1999; 353: 1838–1842

    Article  PubMed  CAS  Google Scholar 

  26. Rauchhaus M, Doehner W, Francis DP et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 2000; 102: 3060–3067

    Article  PubMed  CAS  Google Scholar 

  27. Hummel M, Czerlinski S, Friedel N et al. IL-6 and IL-8 concentrations as predictors in ventricular assist device patients before heart transplantation. Crit Care Med 1994; 22: 448–454

    Article  PubMed  CAS  Google Scholar 

  28. Woiciechowsky C, Schoening B, Cobanov J et al. Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain--injured patients. J Trauma 2002; 52: 339–345

    Article  PubMed  CAS  Google Scholar 

  29. Wang H, Bloom O, Zhang M et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285: 248–251

    Article  PubMed  CAS  Google Scholar 

  30. Slotman GJ. Prospectively validated predictions of shock an dorgan failure in individual septic surgical patients: the systemic mediator associated response test. Crit Care 2000; 4:319–326

    Article  PubMed  CAS  Google Scholar 

  31. Franz AR, Steinbach G, Kron M, Pohlandt F. Reduction of unnecessary antibiotic therapy in newborn infants using IL-8 and C-reactive protein a smarkers of bacterial infections. Pediatrics 1999; 104: 447–453

    Article  PubMed  CAS  Google Scholar 

  32. Meduri GU, Headly S, Kohler G et al. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1ß and IL-6 levels are consitent and efficient predictors of outcome over time. Chest 1995; 107: 1062–1073

    Article  PubMed  CAS  Google Scholar 

  33. Oberhoffer M, Vogelsang H, Russwurm S et al. Outcome prediction by traditional and new markers of inflammation in patients with sepsis. Clin chem Lab Med 1999; 37: 363–368

    Article  PubMed  CAS  Google Scholar 

  34. Spittler A, Razenberger M, Kupper H et al. Relationship between IL-6 plasma concentration in patients with sepsis, monocytes phenotype, monocyte phagocytic properties, an dcytokine production. Clin Infect Dis 2000; 31: 1338–1342

    Article  PubMed  CAS  Google Scholar 

  35. Welborn MB, Oldenburg HS, Hess PJ et al. The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair. Crit Care Med 2000; 28: 3191–3197

    Article  PubMed  CAS  Google Scholar 

  36. Yeh FL, Lin WL, Shen HD, Fang RH. Changes in circulating levels of IL-6 in burned patients. Bursn 1999; 25: 131–136

    Article  CAS  Google Scholar 

  37. Nast-kolb D, Waydhas C, Gippner-Steppert C et al. Indicators of the pottraumatic inflammatory response correlate with organ failure in patients with multiple injuries. J Trauma 1997; 42: 440–454

    Article  Google Scholar 

  38. Reinhart K, Meisner M, Hartog C. Diagnosis of sepsis: novel and conventional parameters. Advances in Sepsis 2001; 1: 42–51

    CAS  Google Scholar 

  39. Assicot M, Gendrel D, Carsin H et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341: 515–518

    Article  PubMed  CAS  Google Scholar 

  40. Meisner M. Procalcitonin. A new, innovative infection parameter. 3rd ed. Stuttgart, Georg Thieme Verl, 2000

    Google Scholar 

  41. Brunkhorst FM, Eberhard OK, Brunkhorst R. Discrimination of infectious an dnoninfectious causes of early acute respiratory distress syndrome by procalcitonin. Crit Care Med 1999; 27: 2172–2176

    Article  PubMed  CAS  Google Scholar 

  42. Maruna P, Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin. Physiol Res 2000; Suppl 1:57–61

    Google Scholar 

  43. Sabat R, Hoeflich C, Doecke WD et al. Massive elevation of procalcitonin plasma levels in th eabsence of infection in kidney transplant patients treated with pan-T cell antibodies. Intensive Care Med 2001; 27: 987–991

    Article  PubMed  CAS  Google Scholar 

  44. Dandona P, Nix D, wilson MF et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab 1994; 79: 1605–1608

    Article  PubMed  CAS  Google Scholar 

  45. Whang KT, Vath SD, Becker KL et al. Procalcitonin an dproinflammatory cytokine interactions in sepsis. Shock 2000; 14: 73–78

    Article  PubMed  CAS  Google Scholar 

  46. Nijsten MW, Olinga P, The TH et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med 2000; 28: 458–461

    Article  PubMed  CAS  Google Scholar 

  47. Redl H, Schiesser A, togel E, Assicot M, Bohuon C. Possible role of TNF on procalcitonin release in a baboon model of sepsis. Shock 2001; 16: 25–27

    Article  PubMed  CAS  Google Scholar 

  48. Cohen J. The detection an dinterpretation of endotoxinemia. intensive Care Med 2000; 26 (Suppl1): 51–56

    Article  Google Scholar 

  49. Hensel M, Volk T, Doecke WD et al. Hypercalcitonemia in patients with noninfectious SIRS and pulmonary dysfunction associated with cardiopulmonary bypass. Anesthesiology 1998; 89: 93–104

    Article  PubMed  CAS  Google Scholar 

  50. Wagner FD, Jonitz B, Potapov EV et al. Procalcitonin, a donor-specific predictor of early graft failure-releated mortality after heart transplantation. Circulation 2001; 104 (12 Suppl1): 1192–196

    Google Scholar 

  51. Russwurm S, Stonans I, Stonane E et al. Procalcitonin and CGRP-1 mRNA expression in various human tissues. Shock 2001; 16: 109–112

    Article  PubMed  CAS  Google Scholar 

  52. Suprin E, Camus C, Gacouin A et al. Procalcitonin: a variable indicator of infection in a medica ICU? Intensive Care Med 2000; 26: 1232–1238

    Article  PubMed  CAS  Google Scholar 

  53. Rosenbloom AJ, Pinsky MR, Napolitano C et al. Suppression of cytokine-mediated beta2-integrin activation on circulating neutrophils in critically ill patients. J Leukoc Biol 1999; 66: 83–89

    PubMed  CAS  Google Scholar 

  54. Woiciechowsky c, Asadullah K, Nestler D et al. Sympathetic activation triggers systemic IL-10 release in immunodepression induced by brain injury. Nat Med 1998; 4: 808–813

    Article  PubMed  CAS  Google Scholar 

  55. Volk HD, Reinke P, Krausch D et al. Monocyte deactivation - rationale for a new therapeutic strategy in sepsis. Intensive Care Med 1996; 22 (Suppl 4): S474–481

    Article  PubMed  Google Scholar 

  56. Haupt W, Riese J, Mehler C et al. Monocyte function before and after surgical trauma. dig Surg 1998; 15: 102–104

    Article  PubMed  CAS  Google Scholar 

  57. Asadullah K, Woiciechowsky C, Doecke WD et al. Immunodepression following neurosurgical procedures. Crit Care Med 1995; 23: 1976–1983

    Article  PubMed  CAS  Google Scholar 

  58. Romaschin AD, Foster DM, Walker PM et al. Let the cells speak: neutrophils as biologic markers of the inflammatory response. Sepsis 1998; 2: 119–125

    Article  Google Scholar 

  59. Kawasaki T, Ogata M, Kawasaki C et al. Surgical stres sinduces endotoxin hyporesponsiveness an dan early decrease of monocyte mCD14 and HLA-DR expression during surgery. Anesth Analg 2001; 92: 1322–1326

    Article  PubMed  CAS  Google Scholar 

  60. Weiss M, Fischer G, Barth E et al. Dissociation of LPS-induced monocytic ex vivo production of G-CSF and TNF-alpha in patients with septic shock. Cytokine 2001; 13: 51–54

    Article  PubMed  CAS  Google Scholar 

  61. Haveman JW, Muller-Kobold AC, Tervaert JW et al. The central role of monocytes in the pathogenesis of sepsis: consequences for immunomonitoring an dtreatment. Neth J Med 1999; 55: 132–141

    Article  PubMed  CAS  Google Scholar 

  62. Heagy W, Hansen C, Nieman K et al. Impaired ex vivo LPS-stimulated whole blood TNF production may identify “septic” intensive care unit patients. Shock 2000; 14: 271–276

    Article  PubMed  CAS  Google Scholar 

  63. Flach R, Majetschak M, Heukamp T et al. Relation of ex vivo stimulated blood cytokine synthesis to post-traumatic sepsis. Cytokine 1999; 11: 173–178

    Article  PubMed  CAS  Google Scholar 

  64. Randow f, Syrbe U, Meisel C et al. Mechanism of endotoxin desensitization - involvement of IL-10 and TGFß. J Exp Med 1995; 55:1887–1892

    Article  Google Scholar 

  65. Doecke WD, Reinke P, Syrbe U et al. Immunoparalysis in sepsis - from phenomenon to treatment strategies. Transplantationsmedizin 1997; 9: 55–65

    Google Scholar 

  66. van den Berk JM, Oldenburger RH, van den Berg AP et al. Low HLA-DR expression on monocytes as a prognostic marker for bacterial sepsis afte rliver transplantation. Transplantation 1997; 63: 1846–1848

    Article  PubMed  Google Scholar 

  67. Stueber F, Book M, Wetegrove S, Schroeder S. The role of genomic polymorphisms in sepsis. Advances in Sepsis 2001; 1: 58–64

    Google Scholar 

  68. Zedler S, bone RC, Baue AE, von Donnersmarck GH, Faist E. T cell reactivity and its predictive role in immunosuppression after burns. Crit Care Med 1999; 27: 66–72

    Article  PubMed  CAS  Google Scholar 

  69. Livingston DH, Appel SH, Wellhausen SR et al. Depressed interferon-gamma production and monocytic HLA-DR expression after severe injury. Arch surg 1988; 123: 1309–1312

    Article  PubMed  CAS  Google Scholar 

  70. Meisel C, Vogt K, Platzer C et al. differential regulation of monocytic TNF-alpha and IL-10 expression. Eur J Immunol 1996; 26: 1580–1586

    Article  PubMed  CAS  Google Scholar 

  71. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996; 24: 1125–1128

    Article  PubMed  CAS  Google Scholar 

  72. Voll RE, Hermann M, Roth EA et al. Immunodepressive effects of apoptotic cells. Nature 1997; 390: 350–351

    Article  PubMed  CAS  Google Scholar 

  73. Hersman MJ, Cheadle WG, Wellhausen SR et al. Monocyte HLA-DR antigen expression characterizes clinical outcome in trauma patient. Br J Surg 1990; 77: 204–207

    Article  Google Scholar 

  74. Asadullah K, Stephanek K, Leupold M et al. IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Invest 1998; 101: 1–12

    Article  Google Scholar 

  75. Wolk K, Doecke WD, vBaehr V et al. Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 2000, 96: 218–223

    PubMed  CAS  Google Scholar 

  76. Eskdale J, Gallagher G, Verweij CL et al. IL-10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA 1998; 95: 9465–9470

    Article  PubMed  CAS  Google Scholar 

  77. Hartung T, Doecke WD, Gantner F et al. Effect of G-CSF treatment on ex vivo blood cytokine response in human volunteers. Blood 1995; 85: 2482–2489

    PubMed  CAS  Google Scholar 

  78. Spittler a, Sautner T, Gornikiewicz A et al. Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery induced decrease in HLA-DR expression on monocytes. Clin Nutr 2001; 20: 37–42

    Article  PubMed  CAS  Google Scholar 

  79. Schinkel C, Licht K, Zedler S et al. Perioperative treatment with human recombinant interferon-gamma: arandonized double-blind clinical trial. Shock 2001; 16: 329–333

    Article  PubMed  CAS  Google Scholar 

  80. Agnes A, Zippel K, Zuckermann H et al. Immune stimulation with G-CSF (Neupogen) in septic patients with immune paralysis. Langenbecks Arch Chir Suppl 1998; 115: 1077–1079

    CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Medical Immunology, University Hospital Charité, Humboldt-University Berlin, Germany

    Hans-Dieter Volk, Conny Hoeflich, Christian Meisel, Gerald Gruetz & Wolf-Dietrich Döcke

  2. Surgery, University Hospital Charité, Humboldt-University Berlin, Germany

    Heidrun Zuckermann

  3. Anaesthesiology and Intensive Care, University Hospital Charité, Humboldt-University Berlin, Germany

    Wolfgang Kox

  4. Neurosurgery, University Hospital Charité, Humboldt-University Berlin, Germany

    Christian Woiciechowsky

  5. Nephrology and Internal Intensive Care, University Hospital Charité, Humboldt-University Berlin, Germany

    Petra Reinke

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  1. Hans-Dieter Volk
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  2. Heidrun Zuckermann
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  4. Christian Woiciechowsky
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  6. Christian Meisel
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  7. Gerald Gruetz
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  9. Petra Reinke
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Editors and Affiliations

  1. Pediatric Critical Care Medicine, Rhode Island Hospital, Providence, RI, USA

    Lesley A. Doughty M.D.

  2. Critical Care Medicine/Infectious Disease, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Peter Linden M.D.

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Volk, HD. et al. (2003). Immune Monitoring and Strategies for Immune Modulation. In: Doughty, L.A., Linden, P. (eds) Immunology and Infectious Disease. Molecular and Cellular Biology of Critical Care Medicine, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0245-6_6

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  • DOI: https://doi.org/10.1007/978-1-4615-0245-6_6

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