Background: Osteoarthritis (OA) in the anterior cruciate ligament (ACL)–deficient knee is seen in approximately 50% of affected patients. Possible causes include biochemical or biomechanical changes. Purpose: We sought to study the correlation between inflammatory cytokines and chondral damage in ACL-deficient knees. Methods: Seventy-six male patients who underwent ACL reconstruction were enrolled in a cross-sectional study. Synovial fluid was aspirated before surgery and analyzed for levels of the inflammatory cytokines tumor necrosis factor-α, interleukin-1 (IL-1), and interleukin-6 (IL-6). At the time of ACL reconstruction, the severity of chondral damage was documented as described by the Outerbridge classification. Results: Patients with grade 2 or higher chondral damage were observed to have elevated IL-6 levels when compared to patients who had no chondral damage. Interleukin-6 levels had no correlation with the duration of injury. Conclusion: Elevated levels of IL-6 in synovial fluid were associated with chondral damage in ACL-deficient knees. Further study is warranted to determine whether inflammatory cytokines contribute to the development of OA of the knee after ACL injury.
AfzalSKhanamA.Serum estrogen and interleukin-6 levels in postmenopausal female osteoarthritis patients. Pak J Pharm Sci. 2011;24(2):217–219.
2.
BareniusBPonzerSShalabiABujakRNorlénLErikssonK.Increased risk of osteoarthritis after anterior cruciate ligament reconstruction: a 14-year follow-up study of a randomized controlled trial. Am J Sports Med. 2014;42(5):1049–1057.
3.
CameronMBuchgraberAPasslerH, et al. The natural history of the anterior cruciate ligament-deficient knee: changes in synovial fluid cytokine and keratan sulfate concentrations. Am J Sports Med. 1997;25(6):751–754.
4.
CameronMLFuFHPaesslerHHSchneiderMEvansCH.Synovial fluid cytokine concentrations as possible prognostic indicators in the ACL-deficient knee. Knee Surg Sports Traumatol Arthrosc. 1994;2(1):38–44.
5.
ChenYJHoM.Research progress on interleukin-6 inhibitors in the treatment of rheumatoid arthritis. Herald Med. 2017;36(6):646–649.
6.
CuellarVGCuellarJMGolishSRYeomansDCScuderiGJ.Cytokine profiling in acute anterior cruciate ligament injury. Arthroscopy. 2010;26(10):1296–1301.
7.
DanielDMStoneMLDobsonBEFithianDCRossmanDJKaufmanKR.Fate of the ACL-injured patient: a prospective outcome study. Am J Sports Med. 1994;22(5):632–644.
8.
HedbomEHäuselmannH.Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation. Cell Mol Life Sci. 2002;59(1):45–53.
9.
HouSMHouCHLiuJF.CX3CL1 promotes MMP-3 production via the CX3CR1, c-Raf, MEK, ERK, and NF-κB signaling pathway in osteoarthritis synovial fibroblasts. Arthritis Res Ther. 2017;19(1):282.
JanssenRPdu MéeAWvan ValkenburgJSalaHATsengCM.Anterior cruciate ligament reconstruction with 4-strand hamstring autograft and accelerated rehabilitation: a 10-year prospective study on clinical results, knee osteoarthritis and its predictors. Knee Surg Sports Traumatol Arthrosc. 2013;21(9):1977–1988.
12.
KanekoSSatohTChibaJJuCInoueKKagawaJ.Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther. 2000;6(2):71–79.
13.
KerinAPatwariPKuettnerKColeAGrodzinskyA.Molecular basis of osteoarthritis: biomechanical aspects. Cell Mol Life Sci. 2002;59(1):27–35.
14.
KesslerMBehrendHHenzSStutzGRukavinaAKusterMS.Function, osteoarthritis and activity after ACL-rupture: 11 years follow-up results of conservative versus reconstructive treatment. Knee Surg Sports Traumatol Arthrosc. 2008;16(5):442–448.
15.
KumarAArshadMSinghA, et al. Role of interleukin-1 super family in progression of osteoarthritis. J Ecophysiol Occup Health. 2017;17(1–2):9–16.
16.
LarssonSEnglundMStruglicsALohmanderS.Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic osteoarthritis in subjects with previous meniscectomy. Osteoarthritis Cartilage. 2015;23:A50–A51.
17.
LatourteACherifiCMailletJ, et al. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann Rheum Dis. 2017;76(4):748–755.
18.
LiRTLorenzSXuYHarnerCDFuFHIrrgangJJ.Predictors of radiographic knee osteoarthritis after anterior cruciate ligament reconstruction. Am J Sports Med. 2011; 39(12):2595–2603.
19.
LivshitsGZhaiGHartDJ, et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford study. Arthritis Rheum. 2009;60(7):2037–2045.
20.
LohmanderLSEnglundPMDahlLLRoosE.The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35(10):1756–1769.
21.
MarksPHDonaldsonMLC. Inflammatory cytokine profiles associated with chondral damage in the anterior cruciate ligament-deficient knee. Arthroscopy. 2005;21(11):1342–1347.
MokhtarNMYusofHYahayaNHMMuhamadRDasS.The transcript level of interleukin-6 in the cartilage of idiopathic osteoarthritis of knee. Clin Ter. 2010;161(1):25–28.
24.
ØiestadBEEngebretsenLStorheimKRisbergM.Winner of the 2008 systematic review competition: knee osteoarthritis after anterior cruciate ligament injury. Am J Sports Med. 2009;37(7):1434–1443.
25.
PapathanasiouIMichalitsisSHantesME, et al. Molecular changes indicative of cartilage degeneration and osteoarthritis development in patients with anterior cruciate ligament injury. BMC Musculoskelet Disord. 2016;17(1):21.
26.
PettipherERHiggsGAHendersonB.Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci USA. 1986;83(22):8749–8753.
27.
QuXWangWTangSLiuYWangJ.Correlation between interleukin-6 expression in articular cartilage bone and osteoarthritis. Genet Mol Res. 2015;14(4):189–195.
28.
SandellLJAignerT.Articular cartilage and changes in arthritis: cell biology of osteoarthritis. Arthritis Res Ther. 2001;3(2):107–113.
29.
Sipe JeanD. Acute-phase proteins in osteoarthritis. Semin Arthritis Rheu. 1995;25(2):75–86.
30.
SriranganSChoyE.The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2010;2(5):247–256.
31.
SwärdPFrobellREnglundMRoosHStruglicsA.Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis)—a cross-sectional analysis. Osteoarthritis Cartilage. 2012;20(11):1302–1308.
32.
van DalenSBlomAJoostenL, et al. Interleukin-1 does not aggravate joint inflammation and cartilage destruction in experimental osteoarthritis. Osteoarthritis Cartilage. 2016; 24:S326.
33.
van DalenSBlomAJoostenLSloetjesA. Joint inflammation and cartilage destruction in experimental osteoarthritis is not mediated by interleukin-1. Ann Rheum Dis. 2016;75(2): 438–438.
34.
van DalenSBlomASlöetjesA, et al. Interleukin-1 is not involved in synovial inflammation and cartilage destruction in collagenase-induced osteoarthritis. Osteoarthritis Cartilage. 2017;25(3):385–396.
35.
VincentTL.IL-1 in osteoarthritis: time for a critical review of the literature. F1000Res. 2019;8:934.
36.
VuolteenahoKKoskinen-KolasaALaavolaMNieminenRMoilanenTMoilanenE.High synovial fluid interleukin-6 levels are associated with increased matrix metalloproteinase levels and severe radiographic changes in osteoarthritis patients. Osteoarthritis Cartilage. 2017;25: S92–S93.
37.
WestacottCISharifM.Cytokines in osteoarthritis: mediators or markers of joint destruction?Semi Arthritis Rheu. 1996;25(4):254–722.
38.
YipRMLYimCW. Role of interleukin 6 inhibitors in the management of rheumatoid arthritis [published online ahead of print December24, 2019]. J Clin Rheumatol. https://doi.org/10.1097/RHU.0000000000001293.
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