Pathogenetic Changes: Isolated Extremity Trauma and Polytrauma

Polytrauma is a term referring to the presence of multiple injuries and thus an array of different pathologies. Fractures of the skeleton are common findings in this setting, with femoral fractures displaying the highest incidence. Overall, isolated polytrauma represents a syndrome with a bandwidth of severities. The body reacts to such an accidental event by means of a “standard” program in order to restore the physiological state.


Trauma Patient Systemic Inflammatory Response Syndrome Multiple Organ Dysfunction Syndrome Multiple Injury Tumour Necrosis Factor Receptor Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Lin E, Lowry SF, Calvano S. The systemic response to injury. In: Schwartz S, Shires GT, Spencer F, editors. Principles of Surgery. New York: McGraw-Hill, 1999: 3–51.Google Scholar
  2. 2.
    Guirao X, Lowry SF. Biologic control of injury and inflammation: much more than too little or too late. World J Surg 1996; 20:437–446.PubMedCrossRefGoogle Scholar
  3. 3.
    Tompkins RG. The role of proinflammatory cytokines in inflammatory and metabolic responses. Ann Surg 1997; 225(3):243–245.PubMedCrossRefGoogle Scholar
  4. 4.
    Nast-Kolb D, Waydhas C, Gippner-Steppert C, Schneider I, Trupka A, Ruchholtz S, Zettl R, Schweiberer L, Jochum M. Indicators of the posttraumatic inflammatory response correlate with organ failure in patients with multiple injuries. J Trauma 1997; 42(3):446–454.PubMedCrossRefGoogle Scholar
  5. 5.
    Keel M, Trentz O. Pathophysiology of polytrauma. Injury 2005; 36:691–709.PubMedCrossRefGoogle Scholar
  6. 6.
    Polk HC, Jr. Non-specific host defense stimulation in the reduction of surgical infection in man. Br J Surg 1987; 74(11):969–970.PubMedCrossRefGoogle Scholar
  7. 7.
    Cipolle MD, Pasquale MD, Cerra FB. Secondary organ dysfunction. From clinical perspectives to molecular mediators. Crit Care Med 1993; 9:261–298.Google Scholar
  8. 8.
    Abraham E. Host defense abnormalities after hemorrhage, trauma, and burns. Crit Care Med 1989; 17(9):934–939.PubMedCrossRefGoogle Scholar
  9. 9.
    Smith RM, Giannoudis PV. Trauma and the immune response. J R Soc Med 1998; 91(8):417–420.PubMedGoogle Scholar
  10. 10.
    Harwood PJ, Giannoudis PV, van Griensven M, Krettek C, Pape H-C. Alterations in the systemic inflammatory response after early total care and damage control procedures for femoral shaft fracture in severely injured patients. J Trauma 2005; 58:446–452.PubMedCrossRefGoogle Scholar
  11. 11.
    Bone RC. Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit Care Med 1996; 24:163–172.PubMedCrossRefGoogle Scholar
  12. 12.
    Davies MG, Hagen P-O. Systemic inflammatory response syndrome. Br J Surg 1997; 84:920–935.PubMedCrossRefGoogle Scholar
  13. 13.
    Regel G, Dwenger A, Gratz KF, Nerlich ML, Sturm JA, Tscherne H. Humorale und zelluläre Veränderungen der unspezifischen Immunabwehr nach schwerem Trauma. Unfallchirurg 1989; 92:314–320.PubMedGoogle Scholar
  14. 14.
    Dinarello CA, Gelfland JA, Wolff SM. Anticytokine strategies in the treatment of the systemic inflammatory response syndrome. JAMA 1993; 269:1829–1835.PubMedCrossRefGoogle Scholar
  15. 15.
    Platzer C, Meisel C, Vogt K, Platzer M, Volk HD. Up-regulation of monocytic IL-10 by tumor necrosis factor-α and cAMP elevating drugs. Int Immunol 1995; 7:517–523.PubMedCrossRefGoogle Scholar
  16. 16.
    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(8):680–687.PubMedGoogle Scholar
  17. 17.
    Bone RC. The pathogenesis of sepsis. Ann Intern Med 1991; 115:457–469.PubMedGoogle Scholar
  18. 18.
    Fukushima R, Alexander JW, Gianotti L, Ogle CK. Isolated pulmonary infection acts as a source of systemic tumor necrosis factor. Crit Care Med 1994; 22:114–120.PubMedGoogle Scholar
  19. 19.
    Regel G, Sturm JA, Pape H-C, Gratz KF, Tscherne H. Das Multiorganversagen (MOV) – Ausdruck eines generalisierten Zellschadens aller Organe nach schwerem Trauma. Unfallchirurg 1991; 94:487–497.PubMedGoogle Scholar
  20. 20.
    Kreuzfelder K, Joka T, Keinecke H-O. Adult respiratory distress syndrome as a specific manifestation of a general permeability defect in trauma patients. Am Rev Respir Dis 1988; 137:95–99.PubMedGoogle Scholar
  21. 21.
    Lucas CE, Ledgerwood AM, Rachwal WJ, Grabow D, Saxe J. Colloid oncotic pressure and body water dynamics in septic and injured patients. J Trauma 1991; 31:927–933.PubMedCrossRefGoogle Scholar
  22. 22.
    Pape H-C, Regel G, Kleemann W, Goris JA, Regel G, Tscherne H. Posttraumatic multiple organ failure – A report on clinical and autopsy findings. Shock 1994; 2(3):228–234.PubMedCrossRefGoogle Scholar
  23. 23.
    Sigurdsson GH, Christenson JT, el-Rakshy MB, Sadek S. Intestinal platelet trapping after traumatic and septic shock. An early sign of sepsis and multiorgan failure in critically ill patients? JAMA 1992; 20:458–467.Google Scholar
  24. 24.
    Gando S, Kameke T, Nanzaki S, Nakanishi Y. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome. Thromb Haemost 1996; 75:224–228.PubMedGoogle Scholar
  25. 25.
    Rinaldo JE, Gorry M, Strieter R, Cowan H, Abdolrasulnia R, Shepherd V. Effect of endotoxin-induced cell injury on 70-kD heat shock proteins in bovine lung endothelial cells. Am J Respir Cell Mol Biol 1990; 3:207–216.PubMedGoogle Scholar
  26. 26.
    Gomez-Jimenez J, Salgado A, Mourelle M, Martín MC, Segura RM, Peracaula R, Moncada S. L-arginine: nitric oxide pathway in endotoxemia and human septic shock. Crit Care Med 1995; 23:253–258.PubMedCrossRefGoogle Scholar
  27. 27.
    Miyauchi T, Tomobe Y, Shiba R, Ishikawa T, Yanagisawa M, Kimura S, Sugishita Y, Ito I, Goto K, Masaki T. Involvement of endothelin in the regulation of human vascular tonus. Potent vasoconstrictor effect and existence in endothelial cells. Circulation 1990; 81:1874–1880.PubMedGoogle Scholar
  28. 28.
    Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure [editorial; comment]. Chest 1992; 101(6):1481–1483.PubMedCrossRefGoogle Scholar
  29. 29.
    Randow F, Syrbe U, Meisel C, Krausch D, Zuckermann H, Platzer C, Volk HD. Mechanisms of endotoxin desensitization: involvement of interleukin-10 and transforming growth factor beta. J Exp Med 1995; 181:1887–1892.PubMedCrossRefGoogle Scholar
  30. 30.
    Syrbe U, Meinecke A, Platzer C, Makki A, Asadullah K, Klug C. Improvement of monocyte function – A new therapeutic approach? In: Reinhart K, Eyrich K, Sprung CL, editors. Sepsis: Current Perspectives in Pathophysiology and Therapy. Berlin: Springer, 1994: 473–500.Google Scholar
  31. 31.
    Mills CD, Caldwell MD, Gann DS. Evidence of a plasma-mediated “window” of immundeficiency in rats following trauma. J Clin Immunol 1989; 9:139–150.PubMedCrossRefGoogle Scholar
  32. 32.
    Kremer JP, Jarrar D, Steckholzer U, Ertel W.. Interleukin-1, -6 and tumor necrosis factor-alpha release is down-regulated in whole blood from septic patients. Acta Haematol 1996; 95(3–4):268–273.PubMedCrossRefGoogle Scholar
  33. 33.
    Bone RC. Why the sepsis trials failed. JAMA 1996; 276(7):565–566.PubMedCrossRefGoogle Scholar
  34. 34.
    Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996; 24:1125–1128.PubMedCrossRefGoogle Scholar
  35. 35.
    Moore FA. The role of the gastrointestinal tract in postinjury multiple organ failure. Am J Surg 1999; 178(6):449–453.PubMedCrossRefGoogle Scholar
  36. 36.
    Volk HD, Lohmann T, Heym S, Golosubow A, Ruppe U, Reinke P, Thieme M, Nieter B, Tausch W, Döcke WD, von Baehr R. Decrease of the proportion of HLA-DR+ monocytes as prognostic parameter for the clinical outcome of septic disease. In: Masihi KN, Lange W, editors. Immunotherapeutic prospects of infectious disease. Berlin: Springer, 1990: 298-301.Google Scholar
  37. 37.
    Seekamp A, Ward PA. Ischemia-reperfusion injury. In: Oppenheim JJ, editor. Inflammatory disease therapy. Basel: Birkhauser Verlag, 1993: 137.Google Scholar
  38. 38.
    Bulger EM, Maier RV. An argument for vitamin E supplementation in the management of systemic inflammatory response syndrome. Shock 2003; 19(2):99-103.PubMedCrossRefGoogle Scholar
  39. 39.
    Nuytinck JK, Goris RJ, Redl H, Schlag G, van Munster OJ. Posttraumatic complications and inflammatory mediators. Arch Surg 1986; 121:886-90.PubMedGoogle Scholar
  40. 40.
    Riedemann NC, Guo RF, Bernacki KD, Reuben JS, Laudes IJ, Neff TA, Gao H, Speyer C, Sarma VJ, Zetoune FS, Ward PA. Regulation by C5a of neutrophil activation during sepsis. Immunity 2003; 19:193-202.PubMedCrossRefGoogle Scholar
  41. 41.
    Harkin DW, Marron CD, Rother RP, Romaschin A, Rubin BB, Lindsay TF. C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm. Br J Surg 2005; 92:1227-34.PubMedCrossRefGoogle Scholar
  42. 42.
    Guo RF, Sun L, Gao H, Shi KX, Rittirsch D, Sarma VJ, Zetoune. FS, and Ward PA. In vivo regulation of neutrophil apoptosis by C5a during sepsis. J Leukoc Biol 2006; 80:1575-83.Google Scholar
  43. 43.
    Wrann CD, Tabriz NA, Barkhausen T, Klos A, van Griensven M, Pape HC, Kendoff DO, Guo R, Ward PA, Krettek C, Riedemann NC. The phosphatidylinositol 3-kinase signaling pathway exerts protective effects during sepsis by controlling C5a-mediated activation of innate immune functions. J Immunol 2007; 178:5940-48.PubMedGoogle Scholar
  44. 44.
    Ayala A, Perrin MM, Meldrum DR, Ertel W, Chaudry IH. Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin. Cytokine 1990; 2:170-74.PubMedCrossRefGoogle Scholar
  45. 45.
    Bogdan C, Vodovotz Y, Nathan C. Macrophage deactivation by interleukin 10. J Exp Med 1991; 174(6):1549-55.PubMedCrossRefGoogle Scholar
  46. 46.
    Meduri GU, Headley S, Kohler G, Kohler G, Tolley E, Leeper KV, Umberger R. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest 1995; 107(4):1062-73.Google Scholar
  47. 47.
    Meduri GU, Kohler G, Headley S, Tolley E, Streutz F, Postlethwaite A. Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest 1995; 108(5):1303-14.Google Scholar
  48. 48.
    van Griensven M, Stalp M, Seekamp A. Ischemia-reperfusion directly increases pulmonary permeability in vitro. Shock 1999; 11(4):259-63.PubMedCrossRefGoogle Scholar
  49. 49.
    Redl H, Schlag G, Kneidinger R, Dinges H, Davies J. Activation/adherence phenomena of leukocytes and endothelial cells in trauma and sepsis. In: Schlag G, Redl H, editors. Pathophysiology of Shock, Sepsis and Organ Failure. Springer-Verlag, pp 33-51,Google Scholar
  50. 50.
    Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 1993; 119:771-778.PubMedGoogle Scholar
  51. 51.
    Ertel W, Kremer JP, Kenney J, Steckholzer U, Jarrar D, Trentz O, Schildberg FW. Downregulation of proinflammatory cytokine release in whole blood from septic patients. Blood 1995; 85(5):1341–1347.PubMedGoogle Scholar
  52. 52.
    Moldawer LL. Interleukin-1, TNF alpha and their naturally occurring antagonists in sepsis. Blood Purif 1993; 11(2):128–133.PubMedCrossRefGoogle Scholar
  53. 53.
    Peschon JJ, Torrance DS, Stocking KL, Glaccum MB, Otten C, Willis CR, Charrier K , Morrissey PJ, Ware CB, Mohler KM. TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J Immunol 1998; 160(2):943–952.PubMedGoogle Scholar
  54. 54.
    Hensler T, Sauerland S, Bouillon B, Raum M, Rixen D, Helling HJ, Andermahr J, Neugebauer EAM. Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase. J Trauma 2002; 52(5):962–970.PubMedCrossRefGoogle Scholar
  55. 55.
    Hildebrand F, Pape H-C, Harwood P, Wittwer T, Krettek C, van Griensven M. Are alterations of lymphocyte subpopulations in polymicrobial sepsis and DHEA treatment mediated by the tumour necrosis factor (TNF)-alpha receptor (TNF-RI)? A study in TNF-RI (TNF-RI(-/-)) knock-out rodents. Clin Exp Immunol 2004; 138:221–229.PubMedCrossRefGoogle Scholar
  56. 56.
    Vandenabeele P, Declercq W, Vanhaesebroeck B, Grooten J, Fiers W. Both TNF receptors are required for TNF-mediated induction of apoptosis in PC60 cells. J Immunol 1995; 154(6):2904–2913.PubMedGoogle Scholar
  57. 57.
    van Griensven M, Wittwer T, Brauer N, Pape H-C. DHEA wirkt protektiv bei einer experimentellen polymikrobiellen Sepsis durch CLP – Besteht eine pathogenetische Bedeutung des TNF-α? Chirurgisches Forum 2001; 30:383-–385.Google Scholar
  58. 58.
    Hubl W, Wolfbauer G, Streicher J, Andert S, Stanek G, Fitzal S, Bayer PM. Differential expression of tumor necrosis factor receptor subtypes on leukocytes in systemic inflammatory response syndrome. Crit Care Med 1999; 27(2):319–324.PubMedCrossRefGoogle Scholar
  59. 59.
    Grell M, Becke FM, Wajant H, Männel DN, Scheurich P. TNF receptor type 2 mediates thymocyte proliferation independently of TNF receptor type 1. Eur J Immunol 1998; 28(1):257–263.PubMedCrossRefGoogle Scholar
  60. 60.
    Stelzner TJ, Weil JV, O’Brien RF. Role of cyclic adenosine monophosphate in the induction of endothelial barrier properties. J Cell Physiol 1989; 139:157–166.PubMedCrossRefGoogle Scholar
  61. 61.
    Tartaglia LA, Goeddel DV, Reynolds C, Figari LS, Weber RF, Fendly BM, Palladino MA. Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor. J Immunol 1993; 151(9):4637–4641.PubMedGoogle Scholar
  62. 62.
    Dinarello CA. The biological properties of interleukin-1. Eur Cytokine Netw 1994; 5(6):517–531.PubMedGoogle Scholar
  63. 63.
    Dinarello CA. The interleukin-1 family: 10 years of discovery. FASEB J 1994; 8(15):1314–1325.PubMedGoogle Scholar
  64. 64.
    Angele MK, Xu YX, Ayala A, Schwacha MG, Catania RK, Cioffi WG, Bland KI, Chaudry IH. Gender dimorphism in trauma-hemorrhage-induced thymocyte apoptosis. Shock 1999; 12(4):316–322.PubMedCrossRefGoogle Scholar
  65. 65.
    Cannon JG, Tompkins RG, Gelfand JA, Michie HR, Stanford GG, van der Meer JW, Endres S, Lonnemann G, Corsetti J Chernow B et al. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis 1990; 161(1):79-84.Google Scholar
  66. 66.
    Schinkel C, Zimmer S, Kremer JP, Walz A, Rordorf-Adam C, Henckel von Donnersmarck G, Faist E. Comparative analysis of transcription and protein release of the inflammatory cytokines interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) following major burn and mechanical trauma. Shock 1995; 4(4):241–246.PubMedCrossRefGoogle Scholar
  67. 67.
    Martin C, Boisson C, Haccoun M, Thomachot L, Mege JL. Patterns of cytokine evolution (tumor necrosis factor-alpha and interleukin-6) after septic shock, hemorrhagic shock, and severe trauma. Crit Care Med 1997; 25(11):1813–1819.PubMedCrossRefGoogle Scholar
  68. 68.
    Pape HC, Remmers D, Grotz M, Schedel I, von Glinski S, Oberbeck R, Dahlweit M, Tscherne H. Levels of antibodies to endotoxin and cytokine release in patients with severe trauma: does posttraumatic dysergy contribute to organ failure? J Trauma 1999; 46(5):907–913.PubMedCrossRefGoogle Scholar
  69. 69.
    Gebhard F, Pfetsch H, Steinbach G, Strecker W, Kinzl L, Bruckner UB. Is interleukin 6 an early marker of injury severity following major trauma in humans? Arch Surg 2000; 135(3):291–295.PubMedCrossRefGoogle Scholar
  70. 70.
    Terregino CA, Lopez BL, Karras DJ, Killian AJ, Arnold GK. Endogenous mediators in emergency department patients with presumed sepsis: are levels associated with progression to severe sepsis and death? Ann Emerg Med 2000; 35(1):26–34.PubMedCrossRefGoogle Scholar
  71. 71.
    Presterl E, Staudinger T, Pettermenn M, Lassnigg A, Burgmann H, Winkler S, Frass M, Graninger W. Cytokine profile and correlation to the APACHE III and MPM II scores in patients with sepsis. Am J Respir Crit Care Med 1997; 156:825–832.PubMedGoogle Scholar
  72. 72.
    Clerici M, Shearer GM. A TH1-->TH2 switch is a critical step in the etiology of HIV infection [see comments]. Immunol Today 1993; 14(3):107–111.PubMedCrossRefGoogle Scholar
  73. 73.
    Pape HC, Grimme K, van Griensven M, Sott AH, Giannoudis P, Morley J, Roise O, Ellingsen E, Hildebrand F, Wiese B, Krettek C. Impact of intramedullary instrumentation versus damage control for femoral fractures on immunoinflammatory parameters: prospective randomized analysis by the EPOFF Study Group. J Trauma 2003; 55(1):7–13.PubMedCrossRefGoogle Scholar
  74. 74.
    Giannoudis PV, Smith RM, Bellamy MC, Morrison JF, Dickson RA, Guillou PJ. Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures. An analysis of the second hit. J Bone Joint Surg Br 1999; 81(2):356–361.PubMedCrossRefGoogle Scholar
  75. 75.
    Pape H-C, Stalp M, van Griensven M, Weinberg A, Dahlweit M, Tscherne H. Optimaler Zeitpunkt der Sekundäroperation bei Polytrauma. Chirurg 1999; 70:1287–1293.PubMedCrossRefGoogle Scholar
  76. 76.
    Pape HC, van Griensven M, Rice J, Gansslen A, Hildebrand F, Zech S, Winny M, Lichtinghagen R, Krettek C. Major secondary surgery in blunt trauma patients and perioperative cytokine liberation: determination of the clinical relevance of biochemical markers. J Trauma 2001; 50(6):989–1000.PubMedCrossRefGoogle Scholar
  77. 77.
    Pape H-C, Schmidt RE, Rice J, van Griensven M, das Gupta R, Krettek C, Tscherne H. Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden. Crit Care Med 2000; 28(10):3441–3448PubMedCrossRefGoogle Scholar
  78. 78.
    Frink M, Pape H-C, van Griensven M, Krettek C, Chaudry IH, Hildebrand F. Influence of sex and age on mods and cytokines after multiple injuries. Shock 2007; 27:151–156.PubMedCrossRefGoogle Scholar
  79. 79.
    Wolk K, Docke W, von Baehr V, Volk H, Sabat R. Comparison of monocyte functions after LPS- or IL-10-induced reorientation: importance in clinical immunoparalysis. Pathobiology 1999; 67(5–6):253–256.PubMedCrossRefGoogle Scholar
  80. 80.
    Neidhardt R, Keel M, Steckholzer U, Safret A, Ungethuem U, Trentz O, Ertel W. Relationship of interleukin-10 plasma levels to severity of injury and clinical outcome in injured patients. J Trauma 1997; 42(5):863–870.PubMedCrossRefGoogle Scholar
  81. 81.
    Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC. Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis. Intensive Care Med 2000; 26(8):1076–1081.PubMedCrossRefGoogle Scholar
  82. 82.
    Steinhauser ML, Hogaboam CM, Kunkel SL, Lukacs NW, Stricter RM, Standiford TJ. IL-10 is a major mediator of sepsis-induced impairment in lung antibacterial host defense. J Immunol 1999; 162:392–399.PubMedGoogle Scholar
  83. 83.
    Song GY, Chung C-S, Chaudry IH, Ayala A. What is the role of interleukin 10 in polymicrobial sepsis: anti-inflammatory agent or immunosuppressant? Surgery 1999; 126:378–383.PubMedGoogle Scholar
  84. 84.
    van der Poll T, Marchant A, Buurman WA, Berman L, Keogh CV, Lazarus DD, Nguyen L, Goldman M, Moldawer LL, Lowry SF. Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol 1995; 155(11):5397–5401.PubMedGoogle Scholar
  85. 85.
    Spagnoli GC, Juretic A, Rosso R, Van Bree J, Harder F, Heberer M. Expression of HLA-DR in granulocytes of polytraumatized patients treated with recombinant human granulocyte macrophage-colony-stimulating factor. Hum Immunol 1995; 43(1):45–50.PubMedCrossRefGoogle Scholar
  86. 86.
    Drossou-Agakidou V, Kanakoudi-Tsakalidou F, Sarafidis K, Tzimouli V, Taparkou A, Kremenopoulos G, Germenis A. In vivo effect of rhGM-CSF and rhG-CSF on monocyte HLA-DR expression of septic neonates. Cytokine 2002; 18(5):260–265.PubMedCrossRefGoogle Scholar
  87. 87.
    Caulfield JJ, Fernandez MH, Sousa AR, Lane SJ, Lee TH Hawrylowicz, CM. Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor in the presence of glucocorticoids. Immunology 1999; 98(1):104–110.Google Scholar
  88. 88.
    Wu JC, Livingston DH, Hauser CJ, Deitch EA, Rameshwar P. Trauma inhibits erythroid burst-forming unit and granulocyte-monocyte colony-forming unit growth through the production of TGF-beta1 by bone marrow stroma. Ann Surg 2001; 234(2):224–232.PubMedCrossRefGoogle Scholar
  89. 89.
    Flohe S, Borgermann J, Dominguez FE, Majetschak M, Lim L, Kreuzfelder E, Obertacke U, Nast-Kolb D, Schade FU. Influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) on whole blood endotoxin responsiveness following trauma, cardiopulmonary bypass, and severe sepsis. Shock 1999; 12(1):17–24.PubMedCrossRefGoogle Scholar
  90. 90.
    Austin OM, Redmond HP, Watson WG, Cunney RJ, Grace PA, Bouchier-Hayes D. The beneficial effects of immunostimulation in posttraumatic sepsis. J Surg Res 1995; 59(4):446–449.PubMedCrossRefGoogle Scholar
  91. 91.
    Gennari R, Alexander JW, Gianotti L, Eaves-Pyles T, Hartmann S. Granulocyte macrophage colony-stimulating factor improves survival in two models of gut-derived sepsis by improving gut barrier function and modulating bacterial clearance. Ann Surg 1994; 220(1):68–76.PubMedCrossRefGoogle Scholar
  92. 92.
    Nierhaus A, Montag B, Timmler N, Frings DP, Gutensohn K, Jung R, Schneider CG, Pothmann W, Brassel AK, Schulte Am Esch J. Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis. Intensive Care Med 2003; 29(4):646–651.PubMedGoogle Scholar
  93. 93.
    Botha AJ, Moore FA, Moore EE, Sauaia A, Banerjee A, Peterson VM. Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure. J Trauma 1995; 39:411–417.PubMedCrossRefGoogle Scholar
  94. 94.
    Botha AJ, Moore FA, Moore EE. Postinjury neutrophil priming and activation: an early vulnerable window. Surgery 1995; 118:358.PubMedCrossRefGoogle Scholar
  95. 95.
    Korthuis RJ, Grisham MB, Granger DN. Leucocyte depletion attenuates vascular injury in postischemic skeletal muscle. Am J Physiol 1988; 254:H823–H827.PubMedGoogle Scholar
  96. 96.
    Vedder NB, Fouty BW, Winn RK, Harlan JM, Rice CL. Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock. Surgery 1989; 106:509–516.PubMedGoogle Scholar
  97. 97.
    Fujishima S, Aikawa N. Neutrophil-mediated tissue injury and its modulation. Intensive Care Med 1995; 21(3):277–285.PubMedCrossRefGoogle Scholar
  98. 98.
    Ertel W, Keel M, Ungethum U, Trentz O. Proinflammatorische Zytokine regulieren die Apoptose von Granulozyten während der systemischen Entzundung. Langenbecks Arch Chir Suppl Kongressbd 1997; 114:627–629.Google Scholar
  99. 99.
    Jimenez MF, Watson RW, Parodo J, Evans D, Foster D, Steinberg M, Rotstein OD, Marshall JC. Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome. Arch Surg 1997; 132(12):1263–1269.PubMedGoogle Scholar
  100. 100.
    Zallen G, Moore EE, Johnson JL, Tamura DY, Aiboshi J, Biffl WL, Silliman CC. Circulating postinjury neutrophils are primed for the release of proinflammatory cytokines. J Trauma 1999; 46(1):42–48.PubMedCrossRefGoogle Scholar
  101. 101.
    Mullen PG, Windsor AC, Walsh CJ, Cook DJ, Fisher BJ, Blocher CR, Leeper-Woodford SK, Sugerman HJ, Fowler AA III. Tumor necrosis factor-alpha and interleukin-6 selectively regulate neutrophil function in vitro. J Surg Res 1995; 58(2):124–130.PubMedCrossRefGoogle Scholar
  102. 102.
    Call DR, Nemzek JA, Ebong SJ, Bolgos GL, Newcomb DE, Remick DG. Ratio of local to systemic chemokine concentrations regulates neutrophil recruitment. Am J Pathol 2001; 158:715–721.PubMedGoogle Scholar
  103. 103.
    Pape H-C, Remmers D, Grotz M, Kotzerke J, von Glinski S, van Griensven M, Dahlweid M, Sznidar S, Tscherne H. Reticuloendothelial system activity and organ failure in patients with multiple injuries. Arch Surg 1999; 134:421–427.PubMedCrossRefGoogle Scholar
  104. 104.
    van Griensven M, Kuzu M, Breddin M, Bottcher F, Krettek C, Pape HC, Tschernig T. Polymicrobial sepsis induces organ changes due to granulocyte adhesion in a murine two hit model of trauma. Exp Toxic Pathol 2002; 54:203–209.CrossRefGoogle Scholar
  105. 105.
    Kurose I, Anderson DC, Miyasaka M, Tamatani T, Paulson JC, Todd RF, Rusche JR, Granger DN. Molecular determinants of reperfusion-induced leukocyte adhesion and vascular protein leakage. Circ Res 1994; 74:336–343.PubMedGoogle Scholar
  106. 106.
    Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 1991; 67:1033–1036.PubMedCrossRefGoogle Scholar
  107. 107.
    Bargatze RF, Kurk S, Watts G, Kishimoto T K, Speer CA, Jutila MA. In vivo and in vitro functional examination of a conserved epitope of L- and E-Selectin crucial for leukocyte-endothelial cell interactions. J Immunol 1994; 152:5814–5825.Google Scholar
  108. 108.
    Springer TA. Adhesion receptors of the immune system. Nature 1990; 346:425–434.PubMedCrossRefGoogle Scholar
  109. 109.
    van Griensven M, Probst C, Müller K, Hoevel P, Pape HC. Leukocyte-endothelial interactions via ICAM-1 are detrimental in polymicrobial sepsis. Shock 2006; 25:254–259.PubMedCrossRefGoogle Scholar
  110. 110.
    Barkhausen T, Krettek C, van Griensven M. L-selectin: adhesion, signalling and its importance in pathologic posttraumatic endotoxemia and non-septic inflammation. Exp Toxic Pathol 2005; 57:39–52.CrossRefGoogle Scholar
  111. 111.
    Kerner T, Ahlers O, Spielmann S, Keh D, Buhrer C, Gerlach M, Hofler S, Gerlach H.. L-selectin in trauma patients: a marker for organ dysfunction and outcome? Eur J Clin Invest 1999; 29(12):1077–1086.PubMedCrossRefGoogle Scholar
  112. 112.
    Seekamp A, van Griensven M, Hildebrandt F, Brauer N, Jochum M, Martin M. The effect of trauma on neutrophil L-selectin expression and sL-selectin serum levels. Shock 2001; 15(4):254-60.PubMedCrossRefGoogle Scholar
  113. 113.
    Muller JC, Buhrer C, Kiening KL, Kerner T, Gerlach H, Obladen M, Unterberg AW, Lanksch WR. Decreased soluble adhesion moleculeL-selectin plasma concentrations after major trauma. J Trauma 1998; 45(4):705–708.PubMedCrossRefGoogle Scholar
  114. 114.
    Maekawa K, Futami S, Nishida M, Terada T, Inagawa H, Suzuki S, Ono K. Effects of trauma and sepsis on soluble L-Selectin and cell surface expression of L-selectin and CD11b. J Trauma 1998; 44(3):460–467.PubMedCrossRefGoogle Scholar
  115. 115.
    Cocks RA, Chan TY, Rainer TH. Leucocyte L-selectin is up-regulated after mechanical trauma in adults. J Trauma 1998; 45(1):1–6.PubMedCrossRefGoogle Scholar
  116. 116.
    van Griensven M, Barkhausen T, Hildebrand F et al. L-selectin shows time and gender dependency in association with MODS. Injury 2004; 35:1087–1095.PubMedCrossRefGoogle Scholar
  117. 117.
    Ahmed NA, Christou NV. Decreased neutrophil L-selectin expression in patients with systemic inflammatory response syndrome. Clin Invest Med 1996; 19(6):427–434.PubMedGoogle Scholar
  118. 118.
    McGill SN, Ahmed NA, Hu F, Michel RP, Christou NV. Shedding of L-selectin as a mechanism for reduced polymorphonuclear neutrophil exudation in patients with the systemic inflammatory response syndrome. Arch Surg 1996; 131:1141–1147.PubMedGoogle Scholar
  119. 119.
    Stengel D, Orth M, Tauber R, Sehouli J, Hentsch S, Thielemann H, Laun R, Ekkernkamp A. Shed L-selectin (sCD62L) load in trauma patients. J Surg Res 2001; 99:321–327.PubMedCrossRefGoogle Scholar
  120. 120.
    Schlag G, Redl H, Till GO, Davies J, Martin U, Dumont L. Anti-L-selectin antibody treatment of hemorrhagic-traumatic shock in baboons. Crit Care Med 1999; 27(9):1900–1907.PubMedCrossRefGoogle Scholar
  121. 121.
    Ramamoorthy C, Sharar SR, Harlan JM, Tedder TF, Winn RK. Blocking L-selectin function attenuates reperfusion injury following hemorrhagic shock in rabbits. Am J Physiol 1996; 271:H1871–H1877.PubMedGoogle Scholar
  122. 122.
    Seekamp A, Regel G, Rother K, Jutila M. The effect of anti-L-selectin (EL-246) on remote lung injury after infrarenal ischemia/reperfusion. Shock 1997; 7(6):447–454.PubMedCrossRefGoogle Scholar
  123. 123.
    Redl H, Martin U, Khadem A, Pelinka LE, van Griensven M. Anti-L-selectin antibody therapy does not worsen the postseptic course in a baboon model. Crit Care 2005; 9:R735–R744.PubMedCrossRefGoogle Scholar
  124. 124.
    Seekamp A, van Griensven M, Breyhahn K, Pohlemann T. The effect of fucoidin on the remote pulmonary injury in a two-hit trauma model in mice. Eur J Trauma 2001; 27(6):317–326.Google Scholar
  125. 125.
    Seekamp A, van Griensven M, Dhondt E, Diefenbeck M, Demeyer I, Vundelinckx G, Haas N, Schaechinger U, Wolowicka L, Rammelt S. The effect of anti-L-selectin (aselizumab) in multiply traumatized patients – Results of a phase II clinical trial. Crit Care Med 2004; 32:2021–2028.PubMedCrossRefGoogle Scholar
  126. 126.
    Rothlein R, Dustin ML, Marlin SD, Springer TA. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 1986; 137:1270–1274.PubMedGoogle Scholar
  127. 127.
    Staunton DE, Dustin ML, Springer TA. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature 1989; 339:61–64.PubMedCrossRefGoogle Scholar
  128. 128.
    Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 1988; 52:925–933.PubMedCrossRefGoogle Scholar
  129. 129.
    Tsokos M, Fehlauer F. Post-mortem markers of sepsis: an immunohistochemical study using VLA-4 (CD49d/CD29) and ICAM-1 (CD54) for the detection of sepsis-induced lung injury. Int J Legal Med 2001; 114(4–5):291–294.PubMedCrossRefGoogle Scholar
  130. 130.
    Muller Kobold AC, Tulleken JE, Zijlstra JG, Sluiter W, Hermans J, Kallenberg CG. Leukocyte activation in sepsis; correlations with disease state and mortality. Intensive Care Med 2000; 26(7):883–892.PubMedCrossRefGoogle Scholar
  131. 131.
    Menges T, Engel J, Welters I, Wagner RM, Little S, Ruwoldt R, Wollbrueck M, Hempelmann G. Changes in blood lymphocyte populations after multiple trauma: association with posttraumatic complications. Crit Care Med 1999; 27(4):733–740.PubMedCrossRefGoogle Scholar
  132. 132.
    Fosse E, Trumpy JH, Skulberg A. Alterations in T-helper and T-suppressor lymphocyte populations after multiple injuries. Injury 1987; 18(3):199–202.PubMedCrossRefGoogle Scholar
  133. 133.
    Cheadle WG, Pemberton RM, Robinson D, Livingston DH, Rodriguez JL, Polk HC Jr. Lymphocyte subset responses to trauma and sepsis. J Trauma 1993; 35(6):844–849.PubMedCrossRefGoogle Scholar
  134. 134.
    Pellegrini JD, De AK, Kodys K, Puyana JC, Furse RK, Miller-Graziano C. Relationships between T lymphocyte apoptosis and anergy following trauma. J Surg Res 2000; 88(2):200–206.PubMedCrossRefGoogle Scholar
  135. 135.
    Hotchkiss RS, Schmieg RE, Jr., Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Karl IE, Buchman TG. Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in patients with trauma and shock. Crit Care Med 2000; 28(9):3207–3217.PubMedCrossRefGoogle Scholar
  136. 136.
    Faist E, Schinkel C, Zimmer S, Kremer JP, Von Donnersmarck GH, Schildberg FW. Inadequate interleukin-2 synthesis and interleukin-2 messenger expression following thermal and mechanical trauma in humans is caused by defective transmembrane signalling. J Trauma 1993; 34(6):846–853.PubMedCrossRefGoogle Scholar
  137. 137.
    Wick M, Kollig E, Muhr G, Koller M. The potential pattern of circulating lymphocytes TH1/TH2 is not altered after multiple injuries. Arch Surg 2000; 135(11):1309–1314.PubMedCrossRefGoogle Scholar
  138. 138.
    van Griensven M, Dahlweid M, Giannoudis PV, Wittwer T, Bottcher F, Breddin M, Pape HC. Dehydroepiandrosterone (DHEA) modulates the activity and the expression of lymphocyte subpopulations induced by cecal ligation and puncture. Shock 2002; 18(5):445–449.PubMedCrossRefGoogle Scholar
  139. 139.
    Carson WE, Yu H, Dierksheide J, Pfeffer K, Bouchard P, Clark R, Durbin J, Baldwin AS, Peschon J, Johnson PR, Ku G, Baumann H, Caligiuri MA. A fatal cytokine-induced systemic inflammatory response reveals a critical role for NK cells. J Immunol 1999; 162:4943–4951.PubMedGoogle Scholar
  140. 140.
    Godshall CJ, Scott MJ, Burch PT, Peyton JC, Cheadle WG. Natural killer cells participate in bacterial clearance during septic peritonitis through interactions with macrophages. Shock 2003; 19(2):144–149.PubMedCrossRefGoogle Scholar
  141. 141.
    Faist E, Mewes A, Strasser T, Walz A, Alkan S, Baker C, Ertel W, Heberer G. Alteration of monocyte function following major injury. Arch Surg 1988; 123(3):287–292.PubMedGoogle Scholar
  142. 142.
    Keel M, Schregenberger N, Steckholzer U, Ungethüm U, Kenney J, Trentz O, Ertel W. Endotoxin tolerance after severe injury and its regulatory mechanisms. J Trauma 1996; 41(3):430–437.PubMedCrossRefGoogle Scholar
  143. 143.
    Kruger C, Schutt C, Obertacke U, Joka T, Müller FE, Knöller J, Köller M, König W, Schönfeld W. Serum CD14 levels in polytraumatized and severely burned patients. Clin Exp Immunol 1991; 85(2):297–301.PubMedCrossRefGoogle Scholar
  144. 144.
    Carrillo EH, Gordon L, Goode E, Davis E, Polk HC Jr. Early elevation of soluble CD14 may help identify trauma patients at high risk for infection. J Trauma 2001; 50(5):810–816.PubMedCrossRefGoogle Scholar
  145. 145.
    Livingston DH, Appel SH, Wellhausen SR, Sonnenfeld G, Polk HC Jr. Depressed interferon gamma production and monocyte HLA-DR expression after severe injury. Arch Surg 1988; 123(11):1309–1312.PubMedGoogle Scholar
  146. 146.
    Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma 1997; 42(5):857–861.PubMedCrossRefGoogle Scholar
  147. 147.
    MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma 2003; 55(1):39–44.PubMedCrossRefGoogle Scholar
  148. 148.
    Kaufmann CR, Dwyer KM, Crews JD, Dols SJ, Trask AL. Usefulness of thrombelastography in assessment of trauma patient coagulation. J Trauma 1997; 42(4):716–720.PubMedCrossRefGoogle Scholar
  149. 149.
    Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003; 54(6):1127–1130.PubMedCrossRefGoogle Scholar
  150. 150.
    Practice Guidelines for blood component therapy: A report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology 1996; 84(3):732–747.Google Scholar
  151. 151.
    Hardy JF, De Moerloose P, Samama M. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anaesth 2004; 51(4):293–310.PubMedCrossRefGoogle Scholar
  152. 152.
    Dutton RP, McCunn M, Hyder M, D’Angelo M, O’Connor J, Hess J, Scalea TM. Factor VIIa for correction of traumatic coagulopathy. J Trauma 2004; 57(4):709–718.PubMedCrossRefGoogle Scholar
  153. 153.
    Martinowitz U, Michaelson M. Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force. J Thromb Haemost 2005; 3(4):640–648.PubMedCrossRefGoogle Scholar
  154. 154.
    Roumen RM, Redl H, Schlag G, Zilow G, Sandtner W, Koller W, Hendriks T, Goris RJA. Inflammatory mediators in relation to the development of multiple organ failure in patients after severe blunt trauma. Crit Care Med 1995; 23(3):474–480.PubMedCrossRefGoogle Scholar
  155. 155.
    Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, Lambris JD, Warner RL, Flierl MA, Hoesel LM, Gebhard F, Younger JG, Drouin SM, Wetsel RA, Ward PA. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 2006; 12:682–687.PubMedCrossRefGoogle Scholar
  156. 156.
    Pape HC, Schmidt RE, Rice J, van Griensven M, Das Gupta R, Krettek C, Tscherne H. Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden. J Orthop Trauma 2004; 18(8 Suppl):S24–S31.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Ludwig Boltzmann Institute for Experimental and Clinical TraumatologyViennaAustria

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