Clinical Rheumatology

, Volume 38, Issue 12, pp 3609–3617 | Cite as

Associations between serum IL-8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis

  • Guangfeng Ruan
  • Jianhua Xu
  • Kang Wang
  • Shuang Zheng
  • Juan Wu
  • Fuqin Bian
  • Bingru Chang
  • Yan Zhang
  • Tao Meng
  • Zhaohua Zhu
  • Weiyu Han
  • Changhai DingEmail author
Original Article



The aim of this study was to investigate cross-sectional associations between serum levels of IL-8 and the above outcomes in patients with knee osteoarthritis (OA).


A total of 160 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Lequesne index were used to assess the joint symptom. Magnetic resonance imaging was used to measure knee structural abnormalities including infrapatellar fat pad (IPFP) signal intensity alternation. Knee radiographic OA was assessed by radiography using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of IL-8 and cartilage or bone biomarkers.


In multivariable analyses, serum IL-8 was positively associated with WOMAC weight-bearing pain (β 2.85, P = 0.028), WOMAC physical dysfunction (β 12.71, P = 0.048), and Lequesne index (β 1.65, P = 0.015), and had positive associations with IPFP signal intensity alteration (OR 3.18, P = 0.011) and serum levels of N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), matrix metalloproteinase (MMP)3, and MMP13 (β 0.24–1.44, all P < 0.05) in patients with clinical knee OA. Furthermore, there were positive associations between IL-8 and WOMAC score (β 22.49, P = 0.037), K-L grades (OR 3.88, P = 0.013), and IPFP signal intensity alteration (OR 3.20, P = 0.033) in patients with radiographic OA.


Serum levels of IL-8 were positively associated with increased knee symptoms, IPFP signal intensity alteration, and serum levels of bone and/or cartilage biomarkers, suggesting that IL-8 may have a role to play in knee OA.

Key Point

This study systemically investigates the associations between serum IL 8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis, and some significant associations have been found, suggesting that IL 8 may have a role to play in knee OA.


IL-8 Magnetic resonance imaging Osteoarthritis 



We appreciate the support of the Department of Rheumatology and Immunology at the First Affiliated Hospital of Anhui Medical University and, of course, all the participants.

Funding information

This study has been supported by the National Natural Science Foundation of China (81172865).

Compliance with ethical standards




  1. 1.
    Wu J, Wang K, Xu J, Ruan G, Zhu Q, Cai J, Ren J, Zheng S, Zhu Z, Otahal P, Ding C (2017) Associations between serum ghrelin and knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee osteoarthritis. Osteoarthr Cartil 25:1428–1435CrossRefGoogle Scholar
  2. 2.
    Cai J, Xu J, Wang K, Zheng S, He F, Huan S, Xu S, Zhang H, Laslett L, Ding C (2015) Association between infrapatellar fat pad volume and knee structural changes in patients with knee osteoarthritis. J Rheumatol 42:1878–1884CrossRefGoogle Scholar
  3. 3.
    Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, Sokolove J (2016) Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol 12:580–592CrossRefGoogle Scholar
  4. 4.
    Pan F, Han W, Wang X, Liu Z, Jin X, Antony B, Cicuttini F, Jones G, Ding C (2015) A longitudinal study of the association between infrapatellar fat pad maximal area and changes in knee symptoms and structure in older adults. Ann Rheum Dis 74:1818–1824CrossRefGoogle Scholar
  5. 5.
    He Y, Liang X, Wu X, Meng C, Wu B, Fu D, Jin S, Yang SH, Wang H (2014) Association between interleukin 8 −251 A/T and +781 C/T polymorphisms and osteoarthritis risk. Immunol Lett 162:207–211CrossRefGoogle Scholar
  6. 6.
    Kaneko S, Satoh T, Chiba J, Ju C, Inoue K (2000) J K. Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther 6:71–79CrossRefGoogle Scholar
  7. 7.
    Monibi F, Roller BL, Stoker A, Garner B, Bal S, Cook JL (2016) Identification of synovial fluid biomarkers for knee osteoarthritis and correlation with radiographic assessment. J Knee Surg 29:242–247CrossRefGoogle Scholar
  8. 8.
    Hulejová H, Barešová V, Klézl Z, Polanská M, Adam M, Šenolt L (2007) Increased level of cytokines and matrix metalloproteinases in osteoarthritic subchondral bone. Cytokine. 38:151–156CrossRefGoogle Scholar
  9. 9.
    Leung YY, Huebner JL, Haaland B, Wong SBS, Kraus VB (2017) Synovial fluid pro-inflammatory profile differs according to the characteristics of knee pain. Osteoarthr Cartil 25:1420–1427CrossRefGoogle Scholar
  10. 10.
    Takahashi A, de Andrés MC, Hashimoto K, Itoi E, Oreffo ROC (2015) Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthr Cartil 23:1946–1954CrossRefGoogle Scholar
  11. 11.
    Yang J, Wang N (2015) Genome-wide expression and methylation profiles reveal candidate genes and biological processes underlying synovial inflammatory tissue of patients with osteoarthritis. Int J Rheum Dis 18:783–790CrossRefGoogle Scholar
  12. 12.
    Kawasaki T, Inoue K (1998) Ushiyama T, S F. Assessment of the American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the knee. Ryumachi. 38:2–5PubMedGoogle Scholar
  13. 13.
    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteoarthrosis. Ann Rheum Dis 16:494–502CrossRefGoogle Scholar
  14. 14.
    Peterfy CG, Guermazi A, Zaim S, Tirman PFJ, Miaux Y, White D, Kothari M, Lu Y, Fye K, Zhao S, Genant HK (2004) Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthr Cartil 12:177–190CrossRefGoogle Scholar
  15. 15.
    Drapé JL, Pessis E, Auleley GR, Chevrot A, Dougados M, Ayral X (1998) Quantitative MR imaging evaluation of chondropathy in osteoarthritic knees. Radiology. 208:49–55CrossRefGoogle Scholar
  16. 16.
    Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, Roemer FW (2011) Evolution of semiquantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthr Cartil / OARS, Osteoarthr Res Soc 19:990–1002CrossRefGoogle Scholar
  17. 17.
    Fenn S, Datir A, Saifuddin A (2009) Synovial recesses of the knee: MR imaging review of anatomical and pathological features. Skelet Radiol 38:317–328CrossRefGoogle Scholar
  18. 18.
    Rai MF, Sandell L (2011) Inflammatory mediators: tracing links between obesity and osteoarthritis, vol 21, pp 131–142Google Scholar
  19. 19.
    Eymard F, Pigenet A, Citadelle D, Flouzat-Lachaniette C-H, Poignard A, Benelli C, Berenbaum F, Chevalier X, Houard X (2014) Induction of an inflammatory and prodegradative phenotype in autologous fibroblast-like synoviocytes by the infrapatellar fat pad from patients with knee osteoarthritis. Arthritis Rheumatol 66:2165–2174CrossRefGoogle Scholar
  20. 20.
    Eymard F, Pigenet A, Citadelle D, Tordjman J, Foucher L, Rose C, Flouzat Lachaniette CH, Rouault C, Clément K, Berenbaum F, Chevalier X, Houard X (2017) Knee and hip intra-articular adipose tissues (IAATs) compared with autologous subcutaneous adipose tissue: a specific phenotype for a central player in osteoarthritis. Ann Rheum Dis 76:1142–1148CrossRefGoogle Scholar
  21. 21.
    Valcamonica E, Chighizola CB, Comi D, De Lucia O, Pisoni L, Murgo A et al (2014) Levels of chemerin and interleukin 8 in the synovial fluid of patients with inflammatory arthritides and osteoarthritis. Clin Exp Rheumatol 32:243–250PubMedGoogle Scholar
  22. 22.
    Xu Q, Chen B, Wang Y, Wang X, Han D, Ding D et al (2017) The effectiveness of manual therapy for relieving pain, stiffness, and dysfunction in knee osteoarthritis: a systematic review and meta-analysis. Pain Physician 20:229–243PubMedGoogle Scholar
  23. 23.
    Davis J, Eaton CB, Lo GH, Lu B, Price LL, McAlindon TE et al (2017) Knee symptoms among adults at risk for accelerated knee osteoarthritis: data from the Osteoarthritis Initiative. Clin Rheumatol 36:1083–1089CrossRefGoogle Scholar
  24. 24.
    Kosek E, Finn A, Ultenius C, Hugo A, Svensson C, Ahmed AS (2018) Differences in neuroimmune signalling between male and female patients suffering from knee osteoarthritis. J Neuroimmunol 321:49–60CrossRefGoogle Scholar
  25. 25.
    Roemer FW, Jarraya M, Felson DT, Hayashi D, Crema MD, Loeuille D, Guermazi A (2016) Magnetic resonance imaging of Hoffa’s fat pad and relevance for osteoarthritis research: a narrative review. Osteoarthr Cartil 24:383–397CrossRefGoogle Scholar
  26. 26.
    Roemer FW, Kwoh CK, Hannon MJ, Hunter DJ, Eckstein F, Fujii T, Boudreau RM, Guermazi A (2015) What comes first? Multitissue involvement leading to radiographic osteoarthritis: magnetic resonance imaging–based trajectory analysis over four years in the osteoarthritis initiative. Arthritis Rheumatol 67:2085–2096CrossRefGoogle Scholar
  27. 27.
    Han W, Aitken D, Zhu Z, Halliday A, Wang X, Antony B, Cicuttini F, Jones G, Ding C (2016) Signal intensity alteration in the infrapatellar fat pad at baseline for the prediction of knee symptoms and structure in older adults: a cohort study. Ann Rheum Dis 75:1783–1788CrossRefGoogle Scholar
  28. 28.
    Sharif M, George E, Dieppe PA (1996) Synovial fluid and serum concentrations of aminoterminal propeptide of type III procollagen in healthy volunteers and patients with joint disease. Ann Rheum Dis 55:47–51CrossRefGoogle Scholar
  29. 29.
    S GN, Kamal W, George J, Manssor E (2017) Radiological and biochemical effects (CTX-II, MMP-3, 8, and 13) of low-level laser therapy (LLLT) in chronic osteoarthritis in Al-Kharj, Saudi Arabia. Lasers Med Sci 32:297–303CrossRefGoogle Scholar
  30. 30.
    Neuhold LA, Killar L, Zhao W, Sung M-LA, Warner L, Kulik J, Turner J, Wu W, Billinghurst C, Meijers T, Poole AR, Babij P, DeGennaro LJ (2001) Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J Clin Investig 107:35–44CrossRefGoogle Scholar
  31. 31.
    Roemer FW, Guermazi A, Zhang Y, Yang M, Hunter DJ, Crema MD, Bohndorf K (2009) Hoffa’s fat pad: evaluation on unenhanced MR images as a measure of patellofemoral synovitis in osteoarthritis. Am J Roentgenol 192:1696–1700CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Guangfeng Ruan
    • 1
    • 2
    • 3
  • Jianhua Xu
    • 1
  • Kang Wang
    • 1
  • Shuang Zheng
    • 1
    • 2
  • Juan Wu
    • 1
  • Fuqin Bian
    • 1
  • Bingru Chang
    • 1
  • Yan Zhang
    • 2
    • 3
  • Tao Meng
    • 2
  • Zhaohua Zhu
    • 2
    • 3
  • Weiyu Han
    • 2
    • 3
  • Changhai Ding
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Rheumatology and Immunology, Arthritis Research Institutethe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Menzies Institute for Medical ResearchUniversity of TasmaniaHobartAustralia
  3. 3.Clinical Research CentreZhujiang Hospital, Southern Medical UniversityGuangzhouChina

Personalised recommendations