Skip to main content
Top
Published in: Intensive Care Medicine 1/2004

01-01-2004 | Original

Influence of surgical intervention in the immune response of severely injured patients

Authors: Sascha Flohé, Sven Lendemans, Fritz-Ulrich Schade, Ernst Kreuzfelder, Christian Waydhas

Published in: Intensive Care Medicine | Issue 1/2004

Login to get access

Abstract

Objective

Primary events such as severe injury and elective surgery cause a deterioration of the immune response measurable by reduction of expression of HLA-DR on monocytes or ex vivo LPS-induced TNFα production. The further influence of secondary surgery after severe injury on the immune response remains unresolved.

Design

Prospective observation study.

Setting

Surgical intensive care unit of an university hospital.

Patients

Sixteen severely injured patients with an ISS >25 points.

Measurements and results

On day 1 after trauma and immediately before secondary surgery, mean fluorescence intensity (MFI) of HLA-DR expression on monocytes and TNFα ex vivo synthesis was significantly reduced compared to healthy donors. Overall, surgical intervention during the second week after trauma caused no further reduction of HLA-DR expression on monocytes and of the ex vivo TNFα-synthesis. However, major surgery such as intramedullary nailing or pelvic osteosynthesis caused reduction of the HLA-DR expression and TNFα-synthesis, whereas, minor surgical interventions such as osteosynthesis on peripheral joints exhibited no significant effects on the immune response. Surgical intervention performed to clear septic foci normalised immune response by elevating HLA-DR expression on monocytes and ex vivo TNFα synthesis. Severe injury caused elevated serum IL-10 levels, whereas secondary surgery did not induce a further increase in serum IL-10 levels.

Conclusion

This study shows that initial trauma as well as major secondary surgery causes a suppression of immune functions, whereas minor secondary surgery does not cause significant immune disturbance.
Literature
1.
go back to reference Ditschkowski M, Kreuzfelder E, Rebmann V, Ferencik S, Majetschak M, Schmid EN, Obertacke U, Hirche H, Schade UF, Grosse-Wilde H (1999) HLA-DR expression and soluble HLA-DR levels in septic patients after trauma. Ann Surg 229:246–254CrossRef Ditschkowski M, Kreuzfelder E, Rebmann V, Ferencik S, Majetschak M, Schmid EN, Obertacke U, Hirche H, Schade UF, Grosse-Wilde H (1999) HLA-DR expression and soluble HLA-DR levels in septic patients after trauma. Ann Surg 229:246–254CrossRef
2.
go back to reference Ditschkowski M, Kreuzfelder E, Majetschak M, Obertacke U, Schade FU, Grosse-Wilde H (1999) Reduced B cell HLA-DR expression and natural killer cell counts in patients prone to sepsis after injury. Eur J Surg 165:1129–1133CrossRef Ditschkowski M, Kreuzfelder E, Majetschak M, Obertacke U, Schade FU, Grosse-Wilde H (1999) Reduced B cell HLA-DR expression and natural killer cell counts in patients prone to sepsis after injury. Eur J Surg 165:1129–1133CrossRef
3.
go back to reference Faist E, Schinkel C, Zimmer S (1996) Update on the mechanisms of immune suppression of injury and immune modulation. World J Surg 20:454–459CrossRef Faist E, Schinkel C, Zimmer S (1996) Update on the mechanisms of immune suppression of injury and immune modulation. World J Surg 20:454–459CrossRef
4.
go back to reference Majetschak M, Flach R, Heukamp T, Jennissen V, Obertacke U, Neudeck F, Schmit-Neuerburg KP, Schade FU (1997) Regulation of whole blood Tumor Necrosis Factor production upon endotoxin stimulation after severe blunt trauma. J Trauma 43:1-8CrossRef Majetschak M, Flach R, Heukamp T, Jennissen V, Obertacke U, Neudeck F, Schmit-Neuerburg KP, Schade FU (1997) Regulation of whole blood Tumor Necrosis Factor production upon endotoxin stimulation after severe blunt trauma. J Trauma 43:1-8CrossRef
5.
go back to reference Keel M, Schregenberger N, Steckholzer U, Ungethum U, Kenney J, Trentz O, Ertel W (1996) Endotoxin tolerance after severe injury and its regulatory mechanisms. J Trauma 41:430–437CrossRef Keel M, Schregenberger N, Steckholzer U, Ungethum U, Kenney J, Trentz O, Ertel W (1996) Endotoxin tolerance after severe injury and its regulatory mechanisms. J Trauma 41:430–437CrossRef
6.
go back to reference Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC (2000) Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent developement of sepsis. Int Care Med 26:1076–1081CrossRef Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC (2000) Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent developement of sepsis. Int Care Med 26:1076–1081CrossRef
7.
go back to reference Fumeaux T, Pugin J (2002) Role of Interleukin-10 in the Intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. Am J Respir Crit Care Med 166:1475–1482CrossRef Fumeaux T, Pugin J (2002) Role of Interleukin-10 in the Intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. Am J Respir Crit Care Med 166:1475–1482CrossRef
8.
go back to reference Asadullah K, Woiciechowsky C, Doecke WD, Liebenthal C, Wauer H, Kox W, Volk HD, Vogel S, Von Baehr R (1995) Immunodepression following neurosurgical procedures. Crit Care Med 23:1976–1983CrossRef Asadullah K, Woiciechowsky C, Doecke WD, Liebenthal C, Wauer H, Kox W, Volk HD, Vogel S, Von Baehr R (1995) Immunodepression following neurosurgical procedures. Crit Care Med 23:1976–1983CrossRef
9.
go back to reference Hiesmayr MJ, Spittler A, Lassnigg A, Berger R, Laufer G, Kocher A, Artemiou O, Boltz-Nitulescu G, Roth E (1999) Alterations in the number of circulating leucocytes, phenotype of monocytes and cytokine production in patients undergoing cardiothoracic surgery Clin Exp Immunol 115:315–323CrossRef Hiesmayr MJ, Spittler A, Lassnigg A, Berger R, Laufer G, Kocher A, Artemiou O, Boltz-Nitulescu G, Roth E (1999) Alterations in the number of circulating leucocytes, phenotype of monocytes and cytokine production in patients undergoing cardiothoracic surgery Clin Exp Immunol 115:315–323CrossRef
10.
go back to reference Decker D, Schondorf M, Bidlingmaier F, Hirner A, von Ruecker AA (1996) Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma. Surgery 119:316–325CrossRef Decker D, Schondorf M, Bidlingmaier F, Hirner A, von Ruecker AA (1996) Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma. Surgery 119:316–325CrossRef
11.
go back to reference Mels AK, Statius Muller MG, van Leeuwen PA, van Blomberg BM, Scheper RJ, Cuesta MA, Beelen RH, Meijer S (2001) Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma. Br J Surg 88:539–544CrossRef Mels AK, Statius Muller MG, van Leeuwen PA, van Blomberg BM, Scheper RJ, Cuesta MA, Beelen RH, Meijer S (2001) Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma. Br J Surg 88:539–544CrossRef
12.
go back to reference Berger D, Bolke E, Seidelmann M, Beger HG (1997) Time-scale of interleukin-6, myeloid related proteins (MRP), C reactive protein (CRP), and endotoxin plasma levels during the postoperative acute phase reaction. Shock 7:422–426CrossRef Berger D, Bolke E, Seidelmann M, Beger HG (1997) Time-scale of interleukin-6, myeloid related proteins (MRP), C reactive protein (CRP), and endotoxin plasma levels during the postoperative acute phase reaction. Shock 7:422–426CrossRef
13.
go back to reference Pape HC, Schmidt RE, Rice J, van Griensven M, das Grupta R, Krettek C, Tscherne H (2000) Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden. Crit Care Med 28:3441–3448CrossRef Pape HC, Schmidt RE, Rice J, van Griensven M, das Grupta R, Krettek C, Tscherne H (2000) Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden. Crit Care Med 28:3441–3448CrossRef
14.
go back to reference Pape HC, Stalp M, van Griensven M, Weinberg A, Dahlweit N, Tscherne H (1999) Optimal timing for secondary surgery in polytrauma patients: an evaluation of 4314 serious-injury cases. Chirurg 70:1287–1293CrossRef Pape HC, Stalp M, van Griensven M, Weinberg A, Dahlweit N, Tscherne H (1999) Optimal timing for secondary surgery in polytrauma patients: an evaluation of 4314 serious-injury cases. Chirurg 70:1287–1293CrossRef
15.
go back to reference Trupka A, Waydhas C, Nast-Kolb D, Schweiberer L (1994) Early intubation in severely injured patients. Eur J Emerg Med 1:1-8CrossRef Trupka A, Waydhas C, Nast-Kolb D, Schweiberer L (1994) Early intubation in severely injured patients. Eur J Emerg Med 1:1-8CrossRef
16.
go back to reference Bone, RC, Balk, RA, Cerra, FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRef Bone, RC, Balk, RA, Cerra, FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRef
17.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996). The SOFA (Sepsis-related Organ Failure Assessment) Score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710CrossRef Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996). The SOFA (Sepsis-related Organ Failure Assessment) Score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710CrossRef
18.
go back to reference Hershman MJ, Cheadle WG, Wellhausen SR, Davidson PF, Polk HC, Jr (1990) Monocyte HLA-DR antigen expression characterises clinical outcome in the trauma patient. Br. J. Surg. 77:204–207CrossRef Hershman MJ, Cheadle WG, Wellhausen SR, Davidson PF, Polk HC, Jr (1990) Monocyte HLA-DR antigen expression characterises clinical outcome in the trauma patient. Br. J. Surg. 77:204–207CrossRef
19.
go back to reference Majetschak M, Flach R, Kreuzfelder E, Jennissen V, Obertacke U, Neudeck F, Schmit-Neuerburg KP, Schade FU (1999) The extent of traumatic damage determines a graded depression of the endotoxin responsiveness of peripheral blood mononuclear cells from patients with blunt injuries. Crit Care Med 27:313–318CrossRef Majetschak M, Flach R, Kreuzfelder E, Jennissen V, Obertacke U, Neudeck F, Schmit-Neuerburg KP, Schade FU (1999) The extent of traumatic damage determines a graded depression of the endotoxin responsiveness of peripheral blood mononuclear cells from patients with blunt injuries. Crit Care Med 27:313–318CrossRef
20.
go back to reference Volk HD, Thieme M, Heym S, Doecke WD, Ruppe U, Tausch W, Manger D, Zuckermann S, Golosubow A, Nieter B (1991) Alterations in function and phenotype of monocytes from patients with septic disease—predictive value and new therapeutic strategies. Behring Inst Mitt 88:208–215 Volk HD, Thieme M, Heym S, Doecke WD, Ruppe U, Tausch W, Manger D, Zuckermann S, Golosubow A, Nieter B (1991) Alterations in function and phenotype of monocytes from patients with septic disease—predictive value and new therapeutic strategies. Behring Inst Mitt 88:208–215
21.
go back to reference Wakefield CH, Carey PD, Foulds S, Monson JR, Guillou PJ (1993) Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 80:205–209CrossRef Wakefield CH, Carey PD, Foulds S, Monson JR, Guillou PJ (1993) Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 80:205–209CrossRef
22.
go back to reference Waydhas C, Nast-Kolb D, Trupka A, Zettl R, Kick M, Wiesholler J, Schweiberer L, Jochum M (1996) Posttraumatic inflammatory response, secondary operations, and late multiple organ failure. J Trauma 40:624–630CrossRef Waydhas C, Nast-Kolb D, Trupka A, Zettl R, Kick M, Wiesholler J, Schweiberer L, Jochum M (1996) Posttraumatic inflammatory response, secondary operations, and late multiple organ failure. J Trauma 40:624–630CrossRef
23.
go back to reference Boelens PG, Houdijk AP, Fonk JC, Nijveldt RJ, Ferwerda CC, Von Blomberg-Van der Flier BM, Thijs LG, Haarman HJ, Puyana JC, Van Leeuwen PA (2002) Glutamine-Enriched Enteral Nutrition Increases HLA-DR Expression on Monocytes of Trauma Patients. J Nutr 132:2580–2586CrossRef Boelens PG, Houdijk AP, Fonk JC, Nijveldt RJ, Ferwerda CC, Von Blomberg-Van der Flier BM, Thijs LG, Haarman HJ, Puyana JC, Van Leeuwen PA (2002) Glutamine-Enriched Enteral Nutrition Increases HLA-DR Expression on Monocytes of Trauma Patients. J Nutr 132:2580–2586CrossRef
24.
go back to reference Waydhas C, Nast Kolb D, Kick M, Trupka A, Zettl R, Wiesholler H, Schmidbauer S, Jochum M, Schweiberer L (1995) Postoperative homeostatic imbalance after trauma surgical interventions of various degrees in polytrauma. Unfallchirurg 98:455–463PubMed Waydhas C, Nast Kolb D, Kick M, Trupka A, Zettl R, Wiesholler H, Schmidbauer S, Jochum M, Schweiberer L (1995) Postoperative homeostatic imbalance after trauma surgical interventions of various degrees in polytrauma. Unfallchirurg 98:455–463PubMed
25.
go back to reference Miller-Graziano CL, Szabo G, Griffey K, Metha B, Kodys K, Catalano D (1991) Role of elevated monocyte transforming growth factor beta (TGFß) production in posttrauma immunosuppression. J Clin Immunol 11:95–102CrossRef Miller-Graziano CL, Szabo G, Griffey K, Metha B, Kodys K, Catalano D (1991) Role of elevated monocyte transforming growth factor beta (TGFß) production in posttrauma immunosuppression. J Clin Immunol 11:95–102CrossRef
26.
go back to reference Ogata M, Okamoto K, Kohriyama K, Kawasaki T, Itoh H, Shigematsu A (2000) Role of Interleukin-10 on hyporesponsiveness of endotoxin during surgery. Crit Care Med 28:3166–3170CrossRef Ogata M, Okamoto K, Kohriyama K, Kawasaki T, Itoh H, Shigematsu A (2000) Role of Interleukin-10 on hyporesponsiveness of endotoxin during surgery. Crit Care Med 28:3166–3170CrossRef
27.
go back to reference Majetschak M, Boergermann J, Waydhas C, Obertacke U, Nast-Kolb D, Schade FU (2000) Whole blood TNFα production and its relationship to systemic concentrations of IL-4, IL-10 and TGF-ß1 in multiply in blunt trauma victims. Crit Care Med 28:1847–1853CrossRef Majetschak M, Boergermann J, Waydhas C, Obertacke U, Nast-Kolb D, Schade FU (2000) Whole blood TNFα production and its relationship to systemic concentrations of IL-4, IL-10 and TGF-ß1 in multiply in blunt trauma victims. Crit Care Med 28:1847–1853CrossRef
28.
go back to reference Boergermann J, Friedrich I, Flohé S, Spillner J, Majetschak M, Kuss O, Sablotzki A, Feldt T, Reidemeister JC, Schade FU (2002) Tumor necrosis factor-α production in whole blood after cardiopulmonary bypass: downregulation caused by circulating cytokine-inhibitory activities. J Thorac Cardiovasc Surg 124:608–617CrossRef Boergermann J, Friedrich I, Flohé S, Spillner J, Majetschak M, Kuss O, Sablotzki A, Feldt T, Reidemeister JC, Schade FU (2002) Tumor necrosis factor-α production in whole blood after cardiopulmonary bypass: downregulation caused by circulating cytokine-inhibitory activities. J Thorac Cardiovasc Surg 124:608–617CrossRef
29.
go back to reference Hubel K, Mansmann G, Schafer H, Oberhauser F, Diehl V, Engert A (2000) Increase of anti-inflammatory cytokines in patients with esophageal cancer after perioperative treatment with G-CSF. Cytokine 12:1797–1800CrossRef Hubel K, Mansmann G, Schafer H, Oberhauser F, Diehl V, Engert A (2000) Increase of anti-inflammatory cytokines in patients with esophageal cancer after perioperative treatment with G-CSF. Cytokine 12:1797–1800CrossRef
30.
go back to reference Schafer H, Hubel K, Bohlen H, Mansmann G, Hegener K, Richarz B, Oberhauser F, Wassmer G, Holscher AH, Pichlmaier H, Diehl V, Engert A (2000) Perioperative treatment with filgrastim stimulates granulocyte function and reduces infectious complications after esophagectomy. Ann Hematol 79:143–151CrossRef Schafer H, Hubel K, Bohlen H, Mansmann G, Hegener K, Richarz B, Oberhauser F, Wassmer G, Holscher AH, Pichlmaier H, Diehl V, Engert A (2000) Perioperative treatment with filgrastim stimulates granulocyte function and reduces infectious complications after esophagectomy. Ann Hematol 79:143–151CrossRef
Metadata
Title
Influence of surgical intervention in the immune response of severely injured patients
Authors
Sascha Flohé
Sven Lendemans
Fritz-Ulrich Schade
Ernst Kreuzfelder
Christian Waydhas
Publication date
01-01-2004
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 1/2004
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-003-2041-3

Other articles of this Issue 1/2004

Intensive Care Medicine 1/2004 Go to the issue