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Published in: Knee Surgery, Sports Traumatology, Arthroscopy 10/2011

01-10-2011 | Knee

Analysis of sequential cytokine release after ACL reconstruction

Authors: A. L. Hayward, D. J. Deehan, R. M. Aspden, A. G. Sutherland

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 10/2011

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Abstract

Purpose

Rupture of the anterior cruciate ligament is common and may necessitate surgical reconstruction. Surgical reconstruction aims to restore normal kinematics and biology within the knee. The acute phase response after surgical reconstruction remains poorly defined but may influence graft integration through modulation of host tissue remodelling.

Methods

The very early host production of key cytokines after surgery was studied. A consecutive series of 14 patients undergoing reconstructive surgery were studied per-operatively, 1 and 6 h after surgery, examining the hypothesis that the acute phase response would be non-specific but consistent between individuals, demonstrating increases of pro-inflammatory cytokines.

Results

A consistent increased release of monocyte-driven, non-specific, IL-1 and IL-6 release but not T cell-derived IL-2 was found. Perhaps, more interestingly, very early high concentrations of secondary growth factors PDGF and TGF-β suggestive of an anabolic response were found.

Conclusion

These data support the contention that an anabolic response starts earlier than previously thought within the surgically reconstructed knee.
Literature
1.
go back to reference Assoian RK, Sporn MB (1986) Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol 102:1217–1223PubMedCrossRef Assoian RK, Sporn MB (1986) Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol 102:1217–1223PubMedCrossRef
2.
go back to reference Bennett NT, Schultz GS (1993) Growth factors and wound healing: part II. role in normal and chronic wound healing. Am J Surg 166:74–81PubMedCrossRef Bennett NT, Schultz GS (1993) Growth factors and wound healing: part II. role in normal and chronic wound healing. Am J Surg 166:74–81PubMedCrossRef
3.
go back to reference Bennett NT, Schultz GS (1993) Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg 165:728–737PubMedCrossRef Bennett NT, Schultz GS (1993) Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg 165:728–737PubMedCrossRef
4.
go back to reference Beynnon BD, Fleming BC, Labovitch R, Parsons B (2002) Chronic anterior cruciate ligament deficiency is associated with increased anterior translation of the tibia during the transition from non-weightbearing to weightbearing. J Orthop Res 20:332–337PubMedCrossRef Beynnon BD, Fleming BC, Labovitch R, Parsons B (2002) Chronic anterior cruciate ligament deficiency is associated with increased anterior translation of the tibia during the transition from non-weightbearing to weightbearing. J Orthop Res 20:332–337PubMedCrossRef
5.
go back to reference Beynnon BD, Johnson RJ, Fleming BC, Kannus P, Kaplan M, Samani J, Renstrom P (2002) Anterior cruciate ligament replacement: comparison of bone-patellar tendon-bone grafts with two-strand hamstring grafts. A prospective, randomized study. J Bone Joint Surg [Am] 84:1503–1513 Beynnon BD, Johnson RJ, Fleming BC, Kannus P, Kaplan M, Samani J, Renstrom P (2002) Anterior cruciate ligament replacement: comparison of bone-patellar tendon-bone grafts with two-strand hamstring grafts. A prospective, randomized study. J Bone Joint Surg [Am] 84:1503–1513
6.
go back to reference Blickenstaff KR, Grana WA, Egle D (1997) Analysis of a semitendinosus autograft in a rabbit model. Am J Sports Med 25:554–559PubMedCrossRef Blickenstaff KR, Grana WA, Egle D (1997) Analysis of a semitendinosus autograft in a rabbit model. Am J Sports Med 25:554–559PubMedCrossRef
7.
go back to reference Border WA, Ruoslahti E (1992) Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest 90:1–7PubMedCrossRef Border WA, Ruoslahti E (1992) Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest 90:1–7PubMedCrossRef
8.
go back to reference Fitzgerald KA, O’Neill AJ, Gearing AJH, Callard RF (2001) The cytokine factsbook. 2nd Edn, Academic Press, London Chapter 2, pp 12–19 Fitzgerald KA, O’Neill AJ, Gearing AJH, Callard RF (2001) The cytokine factsbook. 2nd Edn, Academic Press, London Chapter 2, pp 12–19
9.
go back to reference Cameron ML, Fu FH, Paessler HH, Schneider M, Evans CH (1994) Synovial fluid cytokine concentrations as possible prognostic indicators in the ACL-deficient knee. Knee Surg Sports Traumatol Arthrosc 2:38–44PubMedCrossRef Cameron ML, Fu FH, Paessler HH, Schneider M, Evans CH (1994) Synovial fluid cytokine concentrations as possible prognostic indicators in the ACL-deficient knee. Knee Surg Sports Traumatol Arthrosc 2:38–44PubMedCrossRef
10.
go back to reference Cameron M, Buchgraber A, Paessler H, Vogt M, Thonar E, Fu F, Evans C (1997) The natural history of the anterior cruciate ligament-deficient knee. changes in synovial fluid cytokine and keratan sulfate concentrations. Am J Sports Med 25:751–754PubMedCrossRef Cameron M, Buchgraber A, Paessler H, Vogt M, Thonar E, Fu F, Evans C (1997) The natural history of the anterior cruciate ligament-deficient knee. changes in synovial fluid cytokine and keratan sulfate concentrations. Am J Sports Med 25:751–754PubMedCrossRef
11.
go back to reference Cawston TE, Wilson AJ (2006) Understanding the role of tissue degrading enzymes and their inhibitors in development and disease. Best Pract Res Clin Rheumatol 20:983–1002PubMedCrossRef Cawston TE, Wilson AJ (2006) Understanding the role of tissue degrading enzymes and their inhibitors in development and disease. Best Pract Res Clin Rheumatol 20:983–1002PubMedCrossRef
12.
go back to reference Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC, Cieslak KM, Pringle EK (2010) In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg [Am] 92:599–608CrossRef Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC, Cieslak KM, Pringle EK (2010) In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg [Am] 92:599–608CrossRef
13.
go back to reference Cohen S, Carpenter G (1975) Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci 72:1317–1321PubMedCrossRef Cohen S, Carpenter G (1975) Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci 72:1317–1321PubMedCrossRef
14.
go back to reference Cuellar JM, Scuderi GJ, Cuellar VG, Golish SR, Yeomans DC (2009) Diagnostic utility of cytokine biomarkers in the evaluation of acute knee pain. J Bone Joint Surg [Am] 91:2313–2320CrossRef Cuellar JM, Scuderi GJ, Cuellar VG, Golish SR, Yeomans DC (2009) Diagnostic utility of cytokine biomarkers in the evaluation of acute knee pain. J Bone Joint Surg [Am] 91:2313–2320CrossRef
15.
go back to reference Cuellar JM, Golish SR, Yeomans DC, Scuderi GJ (2010) Cytokine profiling in acute anterior cruciate ligament injury. Arthroscopy 26:1296–1301PubMedCrossRef Cuellar JM, Golish SR, Yeomans DC, Scuderi GJ (2010) Cytokine profiling in acute anterior cruciate ligament injury. Arthroscopy 26:1296–1301PubMedCrossRef
16.
go back to reference Deehan DJ, Cawston TE (2005) The biology of integration of the anterior cruciate ligament. J Bone Joint Surg [Br] 87:889–895CrossRef Deehan DJ, Cawston TE (2005) The biology of integration of the anterior cruciate ligament. J Bone Joint Surg [Br] 87:889–895CrossRef
17.
go back to reference Demirag B, Sarisozen B, Ozer O, Kaplan T, Ozturk C (2005) Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases. J Bone Joint Surg [Am] 87:2401–2410CrossRef Demirag B, Sarisozen B, Ozer O, Kaplan T, Ozturk C (2005) Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases. J Bone Joint Surg [Am] 87:2401–2410CrossRef
18.
go back to reference Dinarello CA (1994) The biological properties of interleukin-1. Eur Cytokine Netw 5:517–531PubMed Dinarello CA (1994) The biological properties of interleukin-1. Eur Cytokine Netw 5:517–531PubMed
19.
go back to reference Duthon VB, Barea C, Abrassart S, Fasel JH, Fritschy D, Menetrey J (2006) Anatomy of the anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 14:204–213PubMedCrossRef Duthon VB, Barea C, Abrassart S, Fasel JH, Fritschy D, Menetrey J (2006) Anatomy of the anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 14:204–213PubMedCrossRef
20.
go back to reference Fibbe WE, Schaafsma MR, Falkenburg JH, Willemze R (1989) The biological activities of interleukin-1. Blut 59:147–156PubMedCrossRef Fibbe WE, Schaafsma MR, Falkenburg JH, Willemze R (1989) The biological activities of interleukin-1. Blut 59:147–156PubMedCrossRef
21.
go back to reference Gearing AJ, Beckett P, Christodoulou M et al (1994) Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 370:555–557PubMedCrossRef Gearing AJ, Beckett P, Christodoulou M et al (1994) Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 370:555–557PubMedCrossRef
22.
go back to reference Gianotti SM, Marshall SW, Hume PA, Bunt L (2009) Incidence of anterior cruciate ligament injury and other knee ligament injuries: a national population-based study. J Sci Med Sport 12:622–627PubMedCrossRef Gianotti SM, Marshall SW, Hume PA, Bunt L (2009) Incidence of anterior cruciate ligament injury and other knee ligament injuries: a national population-based study. J Sci Med Sport 12:622–627PubMedCrossRef
23.
go back to reference Grana WA, Egle DM, Mahnken R, Goodhart CW (1994) An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med 22:344–351PubMedCrossRef Grana WA, Egle DM, Mahnken R, Goodhart CW (1994) An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med 22:344–351PubMedCrossRef
24.
go back to reference Griffin LY, Agel J, Albohm MJ et al (2000) Noncontact anterior cruciate ligament injuries: risk factors and prevention strategies. J Am Acad Orthop Surg 8:141–150PubMed Griffin LY, Agel J, Albohm MJ et al (2000) Noncontact anterior cruciate ligament injuries: risk factors and prevention strategies. J Am Acad Orthop Surg 8:141–150PubMed
25.
go back to reference Higuchi H, Shirakura K, Kimura M, Terauchi M, Shinozaki T, Watanabe H, Takagishi K (2006) Changes in biochemical parameters after anterior cruciate ligament injury. Int Orthop 30:43–47PubMedCrossRef Higuchi H, Shirakura K, Kimura M, Terauchi M, Shinozaki T, Watanabe H, Takagishi K (2006) Changes in biochemical parameters after anterior cruciate ligament injury. Int Orthop 30:43–47PubMedCrossRef
26.
go back to reference Irie K, Uchiyama E, Iwaso H (2003) Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee 10:93–96PubMedCrossRef Irie K, Uchiyama E, Iwaso H (2003) Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee 10:93–96PubMedCrossRef
27.
go back to reference Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM (2001) The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 15:43–58PubMedCrossRef Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM (2001) The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 15:43–58PubMedCrossRef
28.
go back to reference Kapoor B, Clement DJ, Kirkley A, Maffulli N (2004) Current practice in the management of anterior cruciate ligament injuries in the United Kingdom. Br J Sports Med 38:542–544PubMedCrossRef Kapoor B, Clement DJ, Kirkley A, Maffulli N (2004) Current practice in the management of anterior cruciate ligament injuries in the United Kingdom. Br J Sports Med 38:542–544PubMedCrossRef
29.
go back to reference Marks PH, Donaldson MLC (2005) Inflammatory cytokine profiles associated with chondral damage in the anterior cruciate Ligament–Deficient knee. Arthrosc J Arthrosc Relat Surg 21:1342–1347CrossRef Marks PH, Donaldson MLC (2005) Inflammatory cytokine profiles associated with chondral damage in the anterior cruciate Ligament–Deficient knee. Arthrosc J Arthrosc Relat Surg 21:1342–1347CrossRef
30.
go back to reference McFarland EG (1993) The biology of anterior cruciate ligament reconstructions. Orthopedics 16:403–410PubMed McFarland EG (1993) The biology of anterior cruciate ligament reconstructions. Orthopedics 16:403–410PubMed
31.
go back to reference McGeehan GM, Becherer JD, Bast RC Jr et al (1994) Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature 370:558–561PubMedCrossRef McGeehan GM, Becherer JD, Bast RC Jr et al (1994) Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature 370:558–561PubMedCrossRef
32.
go back to reference Menetrey J, Duthon VB, Laumonier T, Fritschy D (2008) “Biological failure” of the anterior cruciate ligament graft. Knee Surg Sports Traumatol Arthrosc 16:224–231PubMedCrossRef Menetrey J, Duthon VB, Laumonier T, Fritschy D (2008) “Biological failure” of the anterior cruciate ligament graft. Knee Surg Sports Traumatol Arthrosc 16:224–231PubMedCrossRef
33.
go back to reference Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22PubMed Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22PubMed
34.
35.
go back to reference Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF (1993) Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg [Am] 75:1795–1803 Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF (1993) Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg [Am] 75:1795–1803
36.
go back to reference Davies PJ, Martin SJ, Burton DR, Roitt IM (2006) Chapter 5, The primary interaction with antigen, in Essential Immunology, Eleventh Edition, Wiley-Blackman, London, pp 86–110 Davies PJ, Martin SJ, Burton DR, Roitt IM (2006) Chapter 5, The primary interaction with antigen, in Essential Immunology, Eleventh Edition, Wiley-Blackman, London, pp 86–110
37.
go back to reference Senthilkumaran S, Tate R, Read J, Sutherland AG (2010) The use of intra-articular morphine in addition to local anaesthetic for post-operative analgesia in anterior cruciate ligament reconstruction: a prospective randomised controlled trial. Knee Surg Sports Traumatol Arthrosc 18:731–735PubMedCrossRef Senthilkumaran S, Tate R, Read J, Sutherland AG (2010) The use of intra-articular morphine in addition to local anaesthetic for post-operative analgesia in anterior cruciate ligament reconstruction: a prospective randomised controlled trial. Knee Surg Sports Traumatol Arthrosc 18:731–735PubMedCrossRef
38.
go back to reference Steed DL (1998) Modifying the wound healing response with exogenous growth factors. Clin Plast Surg 25:397–405PubMed Steed DL (1998) Modifying the wound healing response with exogenous growth factors. Clin Plast Surg 25:397–405PubMed
39.
go back to reference Okada H, Banchereau J, Lotze MT (2003). Interleukin-4. In: Thomson AW, Lotze MT (eds) The cytokine handbook, 4th edn. Academic Press, London, pp 227–264 Okada H, Banchereau J, Lotze MT (2003). Interleukin-4. In: Thomson AW, Lotze MT (eds) The cytokine handbook, 4th edn. Academic Press, London, pp 227–264
40.
go back to reference Tohyama H, Yasuda K (2005) Anterior cruciate ligament (ACL) healing: ACL graft biology. Sports Med Arthrosc Rev 13:156–160CrossRef Tohyama H, Yasuda K (2005) Anterior cruciate ligament (ACL) healing: ACL graft biology. Sports Med Arthrosc Rev 13:156–160CrossRef
41.
go back to reference Tyler TF, McHugh MP, Gleim GW, Nicholas SJ (1999) Association of KT-1000 measurements with clinical tests of knee stability 1 year following anterior cruciate ligament reconstruction. J Orthop Sports Phys Ther 29:540–545PubMed Tyler TF, McHugh MP, Gleim GW, Nicholas SJ (1999) Association of KT-1000 measurements with clinical tests of knee stability 1 year following anterior cruciate ligament reconstruction. J Orthop Sports Phys Ther 29:540–545PubMed
42.
go back to reference Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83:835–870PubMed Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83:835–870PubMed
43.
go back to reference Woo SL, Abramowitch SD, Kilger R, Liang R (2006) Biomechanics of knee ligaments: Injury, healing, and repair. J Biomech 39:1–20PubMedCrossRef Woo SL, Abramowitch SD, Kilger R, Liang R (2006) Biomechanics of knee ligaments: Injury, healing, and repair. J Biomech 39:1–20PubMedCrossRef
44.
go back to reference Yoshiya S, Nagano M, Kurosaka M, Muratsu H, Mizuno K (2000) Graft healing in the bone tunnel in anterior cruciate ligament reconstruction. Clin Orthop Relat Res 376:278–286PubMedCrossRef Yoshiya S, Nagano M, Kurosaka M, Muratsu H, Mizuno K (2000) Graft healing in the bone tunnel in anterior cruciate ligament reconstruction. Clin Orthop Relat Res 376:278–286PubMedCrossRef
45.
go back to reference Zysk SP, Fraunberger P, Veihelmann A et al (2004) Tunnel enlargement and changes in synovial fluid cytokine profile following anterior cruciate ligament reconstruction with patellar tendon and hamstring tendon autografts. Knee Surg Sports Traumatol Arthrosc 12:98–103PubMedCrossRef Zysk SP, Fraunberger P, Veihelmann A et al (2004) Tunnel enlargement and changes in synovial fluid cytokine profile following anterior cruciate ligament reconstruction with patellar tendon and hamstring tendon autografts. Knee Surg Sports Traumatol Arthrosc 12:98–103PubMedCrossRef
Metadata
Title
Analysis of sequential cytokine release after ACL reconstruction
Authors
A. L. Hayward
D. J. Deehan
R. M. Aspden
A. G. Sutherland
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 10/2011
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-011-1486-0

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