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Erschienen in: International Orthopaedics 6/2014

01.06.2014 | Original Paper

Cytokine Levels (IL-4, IL-6, IL-8 and TGFβ) as Potential Biomarkers of Systemic Inflammatory Response in Trauma Patients

verfasst von: Gershon Volpin, Miri Cohen, Michael Assaf, Tamar Meir, Rina Katz, Shimon Pollack

Erschienen in: International Orthopaedics | Ausgabe 6/2014

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Abstract

Purpose

Much research is now being conducted in order to understand the role of cytokines in the development of the inflammatory response following trauma. The purpose of this study was to evaluate whether serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma.

Methods

We conducted a prospective study with 71 individuals of whom 13 (18.3 %) were healthy controls and 58 (81.7 %) were traumatized orthopaedic patients who were categorized into two groups: 31 (43.6 %) with moderate injuries and 27 (38.1 %) patients with severe orthopaedic trauma. Thirty cc of heparinized blood were drawn from each individual within a few hours after the injury. Serum levels of pro-inflammatory, regulatory and anti-inflammatory cytokines were measured in each individual participant.

Results

High levels of pro-inflammatory cytokines IL-1β,-6,-8,-12, tumour necrosis factor alpha and interferon gamma were found in all injured patients compared to healthy controls. Only IL-6 and IL-8 were significantly higher in the injured patients. Levels of the regulatory cytokines, transformed growth factor beta (TGF-β) and IL-10 were higher in the injured patients, but significant only for TGF-β. Levels of IL-4 were significantly lower in the injured groups as compared to the controls.

Conclusions

Secretion of large amounts of pro-inflammatory cytokines and decreased level of anti-inflammatory cytokines during the acute phase of trauma may lead to the development of systemic inflammatory response syndrome (SIRS) in unstable polytraumatized patients. SIRS may result in life threatening conditions as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). High levels of IL-6, IL-8, TGFβ and low levels of IL-4 were found to be reliable markers for the existence of immune reactivity in trauma patients. More research is needed to study pattern of cytokine levels along the acute period of injury, after surgical interventions and during recovery.
Literatur
1.
Zurück zum Zitat Giannoudis PV, Hildebrand F (2004) Pape HC (2004): Inflammatory serum markers in patients with multiple trauma: Can they predict outcome? J Bone Joint Surg Br 86:313–323PubMedCrossRef Giannoudis PV, Hildebrand F (2004) Pape HC (2004): Inflammatory serum markers in patients with multiple trauma: Can they predict outcome? J Bone Joint Surg Br 86:313–323PubMedCrossRef
2.
Zurück zum Zitat Craig S, Roberts CS, Pape HC, Jones AL, Malkani AL, Rodriguez JL, Giannoudis PV (2005) Damage control orthopaedics. Evolving concepts in the treatment of patients who have sustained orthopaedic trauma. J Bone Joint Surg Am 87:434–449 Craig S, Roberts CS, Pape HC, Jones AL, Malkani AL, Rodriguez JL, Giannoudis PV (2005) Damage control orthopaedics. Evolving concepts in the treatment of patients who have sustained orthopaedic trauma. J Bone Joint Surg Am 87:434–449
3.
Zurück zum Zitat Pape HC, Rixen D, Morley J et al (2007) Impact of the method of initial stabilization for femoral shaft fractures in patients with multiple injuries at risk for complications (borderline patients). Ann Surg 246:491–499PubMedCentralPubMedCrossRef Pape HC, Rixen D, Morley J et al (2007) Impact of the method of initial stabilization for femoral shaft fractures in patients with multiple injuries at risk for complications (borderline patients). Ann Surg 246:491–499PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat Sears BW, Strover MD, Callaci J (2009) Pathoanatomy and clinical correlation of the immunoinflamatory response following orthopaedic trauma. J AAOS 17:255–265 Sears BW, Strover MD, Callaci J (2009) Pathoanatomy and clinical correlation of the immunoinflamatory response following orthopaedic trauma. J AAOS 17:255–265
5.
Zurück zum Zitat Lichte P, Kobbe P, Dombroski D, Pape HC (2012) Damage control orthopaedics; current evidence. Curr Opin Crit Care 18:647–650PubMedCrossRef Lichte P, Kobbe P, Dombroski D, Pape HC (2012) Damage control orthopaedics; current evidence. Curr Opin Crit Care 18:647–650PubMedCrossRef
7.
Zurück zum Zitat Giannoudis PV, Smith RM, Bellamy MC, Morrison JF, Dickson RA, Guillou PJ (1999) Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures: An analysis of the second hit. J Bone Joint Surg Br 81:356–361PubMedCrossRef Giannoudis PV, Smith RM, Bellamy MC, Morrison JF, Dickson RA, Guillou PJ (1999) Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures: An analysis of the second hit. J Bone Joint Surg Br 81:356–361PubMedCrossRef
8.
Zurück zum Zitat Pape HC, Hildebrand F, Pertschy S, Zelle B, Garapati R, Grimme K, Krettek C, Reed RL 2nd (2002) Changes in the management of femoral shaft fractures in polytrauma patients: from early total care to damage control orthopedic surgery. J Trauma 53:452–462PubMedCrossRef Pape HC, Hildebrand F, Pertschy S, Zelle B, Garapati R, Grimme K, Krettek C, Reed RL 2nd (2002) Changes in the management of femoral shaft fractures in polytrauma patients: from early total care to damage control orthopedic surgery. J Trauma 53:452–462PubMedCrossRef
9.
Zurück zum Zitat Biffl W, Moore EE, Moore FA, Peterson VM (1996) Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation? Ann Surg 224:647–664PubMedCentralPubMedCrossRef Biffl W, Moore EE, Moore FA, Peterson VM (1996) Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation? Ann Surg 224:647–664PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Menger MD, Vollmar B (2004) Surgical trauma: hyperinflammation versus immunosuppression? Langenbecks Arch Surg 389:475–484PubMedCrossRef Menger MD, Vollmar B (2004) Surgical trauma: hyperinflammation versus immunosuppression? Langenbecks Arch Surg 389:475–484PubMedCrossRef
11.
Zurück zum Zitat Kumbhare D, Parkinson W, Dunlop B, Richards C, Kerr C, Buckley N, Adachi J (2009) Injury measurement properties of serum interleukin-6 following lumbar decompression surgery. J Surg Res 157:161–167PubMedCrossRef Kumbhare D, Parkinson W, Dunlop B, Richards C, Kerr C, Buckley N, Adachi J (2009) Injury measurement properties of serum interleukin-6 following lumbar decompression surgery. J Surg Res 157:161–167PubMedCrossRef
12.
13.
Zurück zum Zitat Copes WS, Lawnick M, Champion HR, Sacco WJ (1988) A comparison of abbreviated injury scale 1980 and 1985 versions. J Trauma 28:78–86PubMedCrossRef Copes WS, Lawnick M, Champion HR, Sacco WJ (1988) A comparison of abbreviated injury scale 1980 and 1985 versions. J Trauma 28:78–86PubMedCrossRef
14.
Zurück zum Zitat Civil ID, Schwab CW (1988) The abbreviated injury scale, 1985 revision; a condensed chart for clinical use. J Trauma 28:87–90PubMedCrossRef Civil ID, Schwab CW (1988) The abbreviated injury scale, 1985 revision; a condensed chart for clinical use. J Trauma 28:87–90PubMedCrossRef
15.
Zurück zum Zitat Baker SP, O’Neill B, Haddon W Jr, Long WB (1988) The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187–196CrossRef Baker SP, O’Neill B, Haddon W Jr, Long WB (1988) The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187–196CrossRef
16.
Zurück zum Zitat Cohen M, Meir T, Klein E, Volpin G, Assaf M, Pollack S (2011) Cytokine levels as potential biomarkers for predicting the development of posttraumatic stress symptoms in casualties of accidents. Int J Psychiatry Med 42:117–131PubMedCrossRef Cohen M, Meir T, Klein E, Volpin G, Assaf M, Pollack S (2011) Cytokine levels as potential biomarkers for predicting the development of posttraumatic stress symptoms in casualties of accidents. Int J Psychiatry Med 42:117–131PubMedCrossRef
17.
Zurück zum Zitat Dinarello CA (1997) Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents 11:91–103PubMed Dinarello CA (1997) Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents 11:91–103PubMed
18.
Zurück zum Zitat Sultani S, Stringer AM, Bowen JM, Gibson RJ (2012) Anti-inflammatory cytokines: important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis. Chemotherapy Res Practice 2012; Article ID 490804, 11 pages doi:10.1155/2012/490804 Sultani S, Stringer AM, Bowen JM, Gibson RJ (2012) Anti-inflammatory cytokines: important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis. Chemotherapy Res Practice 2012; Article ID 490804, 11 pages doi:10.​1155/​2012/​490804
19.
Zurück zum Zitat Ayala A, Meldrum DR, Perrin MM, Chaudry IH (1993) The release of transforming growth factor-beta following haemorrhage: its role as a mediator of host immunosuppression. Immunology 79:479–84PubMedCentralPubMed Ayala A, Meldrum DR, Perrin MM, Chaudry IH (1993) The release of transforming growth factor-beta following haemorrhage: its role as a mediator of host immunosuppression. Immunology 79:479–84PubMedCentralPubMed
20.
Zurück zum Zitat Sarahrudi K, Thomas A, Mousavi M, Kaiser G, Köttstorfer J, Kecht M, Hajdu S, Aharinejad S (2011) Elevated transforming growth factor-beta 1 (TGF-β1) levels in human fracture healing. Injury 42:833–837PubMedCentralPubMedCrossRef Sarahrudi K, Thomas A, Mousavi M, Kaiser G, Köttstorfer J, Kecht M, Hajdu S, Aharinejad S (2011) Elevated transforming growth factor-beta 1 (TGF-β1) levels in human fracture healing. Injury 42:833–837PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor β in human disease. N Engl J Med 342:1350–1358PubMedCrossRef Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor β in human disease. N Engl J Med 342:1350–1358PubMedCrossRef
23.
Zurück zum Zitat Smith RM, Bellamy MC, Morrison JF, Dickson RA, Guillou PJ (1999) Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures: An analysis of the second hit. J Bone Joint Surg Br 81:356–361PubMedCrossRef Smith RM, Bellamy MC, Morrison JF, Dickson RA, Guillou PJ (1999) Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures: An analysis of the second hit. J Bone Joint Surg Br 81:356–361PubMedCrossRef
24.
Zurück zum Zitat Lee CC, Marill KA, Carter WA, Crupi RS (2001) A current concept of trauma-induced multiorgan failure. Ann Emerg Med 38:170–176PubMedCrossRef Lee CC, Marill KA, Carter WA, Crupi RS (2001) A current concept of trauma-induced multiorgan failure. Ann Emerg Med 38:170–176PubMedCrossRef
26.
Zurück zum Zitat Pervanidou P, Kolaitis G, Charitaki S, Margeli A, Ferentinos S, Bakoula C, Lazaropoulou C, Papassotiriou I, Tsiantis J, Chrousos GP (2007) Elevated morning serum interleukin (IL)-6 or evening salivary cortisol concentrations predict posttraumatic stress disorder in children and adolescents six months after a motor vehicle accident. Psychoneuroendocrinology 32:991–999PubMedCrossRef Pervanidou P, Kolaitis G, Charitaki S, Margeli A, Ferentinos S, Bakoula C, Lazaropoulou C, Papassotiriou I, Tsiantis J, Chrousos GP (2007) Elevated morning serum interleukin (IL)-6 or evening salivary cortisol concentrations predict posttraumatic stress disorder in children and adolescents six months after a motor vehicle accident. Psychoneuroendocrinology 32:991–999PubMedCrossRef
27.
Zurück zum Zitat Newport DJ, Nemeroff BC (2000) Neurobiology of posttraumatic stress disorder. Curr Opin Neurobiol 10:211–218PubMedCrossRef Newport DJ, Nemeroff BC (2000) Neurobiology of posttraumatic stress disorder. Curr Opin Neurobiol 10:211–218PubMedCrossRef
28.
Zurück zum Zitat Hoff P, Buttgereit F, Burmester GR, Jakstadt M, Gaber T, Andreas K, Matziolis G, Perka C, Rohner E (2013) Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int Orthopaedics (SICOT) 37:145–151CrossRef Hoff P, Buttgereit F, Burmester GR, Jakstadt M, Gaber T, Andreas K, Matziolis G, Perka C, Rohner E (2013) Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int Orthopaedics (SICOT) 37:145–151CrossRef
29.
Zurück zum Zitat Matsumoto S, Muller-Ladner U, Gay RE, Nishioka K, Gay S (1996) Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts. J Rheumatol 23(8):1345–1352PubMed Matsumoto S, Muller-Ladner U, Gay RE, Nishioka K, Gay S (1996) Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts. J Rheumatol 23(8):1345–1352PubMed
30.
Zurück zum Zitat Rohner E, Matziolis G, Perka C, Fuchtmeier B, Gaber T, Burmester GR, Buttgereit F, Hoff P (2012) Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases. Immunol Res 52(3):169–175PubMedCrossRef Rohner E, Matziolis G, Perka C, Fuchtmeier B, Gaber T, Burmester GR, Buttgereit F, Hoff P (2012) Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases. Immunol Res 52(3):169–175PubMedCrossRef
31.
Zurück zum Zitat Hundric-Hasple Z, Pecina M, Haspl M, Tomicic M, Jukic I (2006) Plasma cytokines as markers of aseptic prosthesis loosening. Clin Orthop Relat Res 453:299–304CrossRef Hundric-Hasple Z, Pecina M, Haspl M, Tomicic M, Jukic I (2006) Plasma cytokines as markers of aseptic prosthesis loosening. Clin Orthop Relat Res 453:299–304CrossRef
Metadaten
Titel
Cytokine Levels (IL-4, IL-6, IL-8 and TGFβ) as Potential Biomarkers of Systemic Inflammatory Response in Trauma Patients
verfasst von
Gershon Volpin
Miri Cohen
Michael Assaf
Tamar Meir
Rina Katz
Shimon Pollack
Publikationsdatum
01.06.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
International Orthopaedics / Ausgabe 6/2014
Print ISSN: 0341-2695
Elektronische ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-013-2261-2

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