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Cited by 510Osteoarthritis Treatment and MechanismsRheumatoid Arthritis Research and TherapiesHip disorders and treatments

Circulating levels of IL-6 and TNF-α are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults

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Stannus, O., Jones, G., Cicuttini, F., Parameswaran, V., Quinn, S., Burgess, J., Ding, C.·2010·Osteoarthritis and Cartilage
DOI 10.1016/j.joca.2010.08.016
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Abstract

Objective The role of inflammation in osteoarthritis (OA) pathogenesis is unclear, and the associations between inflammatory cytokines and cartilage loss have not been reported. We determined the associations between serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), knee radiographic OA (ROA) and cartilage loss over 2.9 years in older adults. Methods A total of 172 randomly selected subjects (mean 63 years, range 52-78, 47% female) were studied at baseline and approximately 3 (range 2.6-3.3) years later. IL-6 and TNF-α were assessed by radioimmunoassay. T1-weighted fat-suppressed magnetic resonance imaging of the right knee was performed at baseline and follow-up to determine knee cartilage volume. Knee ROA of both knees was assessed at baseline. Results At baseline, quartiles of IL-6 and TNF-α were associated with increased prevalence of medial tibiofemoral joint space narrowing (OARSI grade ≥ 1) in multivariate analyses [odds ratio (OR): 1.42 and 1.47 per quartile, respectively, both P<0.05]. Longitudinally, baseline IL-6 predicted loss of both medial and lateral tibial cartilage volume (β: -1.19% and -1.35% per annum per quartile, P<0.05 and P<0.01, respectively), independently of TNF-α. Change in IL-6 was associated with increased loss of medial and lateral tibial cartilage volume (β: -1.18% and -1.06% per annum per quartile, both P<0.05) and change in TNF-α was also negatively associated with change in medial cartilage volume (β: -1.27% per annum per quartile, P<0.05). Conclusions Serum levels of IL-6 and TNF-α are associated with knee cartilage loss in older people suggesting low level inflammation plays a role in the pathogenesis of knee OA.

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  • In osteoarthritis, increased TNF-α levels in synovial fluid might match the degree of symptoms and radiographic change.

    “In those with osteoarthritis, increased TNF-α levels in their synovial fluid might match the degree of their symptoms and the radiographic change of their disease [44].”

    From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [44]

    The Results report that higher TNF-α was associated with medial tibiofemoral joint-space narrowing, a radiographic finding. But the study measured TNF-α in serum, not synovial fluid, and does not establish that it tracks symptom severity; the Discussion notes a prior study found no association between serum TNF-α and knee pain or stiffness. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Research works printed but not linked: 36

  1. Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med 2006;354:841e8.
  2. Ding C, Cicuttini F, Blizzard L, Jones G. Smoking interacts with family history with regard to knee cartilage loss and cartilage defect development. Arthritis Rheum 2007;56:1521e8.
  3. Ding C, Cicuttini F, Jones G. Tibial subchondral bone size and knee cartilage defects: relevance to knee osteoarthritis. Oste- oarthritis Cartilage 2007;15:479e86.
  4. Ding C, Parameswaran V, Cicuttini F, Burgess J, Zhai G, Quinn S, et al. Association between leptin, body composition, sex and knee cartilage morphology in older adults: the Tasmanian Older Adult Cohort (TASOAC) study. Ann Rheum Dis 2008;67:1256e61.
  5. Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005;64:1263e7.
  6. Hill CL, Hunter DJ, Niu J, Clancy M, Guermazi A, Genant H, et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis 2007;66:1599e603.
  7. Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M. Synovitis: a potential predictive factor of struc- tural progression of medial tibiofemoral knee osteoarthritis e results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage 2005;13:361e7.
  8. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 2001;44:1237e47.
  9. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteo- arthritis. Arthritis Res Ther 2006;8:R187.
  10. Partsch G, Steiner G, Leeb BF, Dunky A, Broll H, Smolen JS. Highly increased levels of tumor necrosis factor-alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid. J Rheumatol 1997;24:518e23.
  11. Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol 1997;24: 365e71.
  12. Vignon E, Balblanc JC, Mathieu P, Louisot P, Richard M. Met- alloprotease activity, phospholipase A2 activity and cytokine concentration in osteoarthritis synovial fluids. Osteoarthritis Cartilage 1993;1:115e20.
  13. Huebner JL, Seifer DR, Kraus VB. A longitudinal analysis of serum cytokines in the Hartley guinea pig model of osteoar- thritis. Osteoarthritis Cartilage 2007;15:354e6.
  14. Kobayashi M, Squires GR, Mousa A, Tanzer M, Zukor DJ, Antoniou J, et al. Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum 2005;52:128e35.
  15. Spector TD, Hart DJ, Nandra D, Doyle DV, Mackillop N, Gallimore JR, et al. Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 1997;40:723e7.
  16. Sharif M, Shepstone L, Elson CJ, Dieppe PA, Kirwan JR. Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee. Ann Rheum Dis 2000;59:71e4.
  17. Hanna FS, Bell RJ, Cicuttini FM, Davison SL, Wluka AE, Davis SR. High sensitivity C-reactive protein is associated with lower tibial cartilage volume but not lower patella cartilage volume in healthy women at mid-life. Arthritis Res Ther 2008;10:R27.
  18. Livshits G, Zhai G, Hart DJ, Kato BS, Wang H, Williams FMK, et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford Study. Arthritis Rheum 2009;60:2037e45.
  19. Botha-Scheepers S, Watt I, Slagboom E, de Craen AJ, Meulenbelt I, Rosendaal FR, et al. Innate production of tumour necrosis factor alpha and interleukin 10 is associated with radiological progression of knee osteoarthritis. Ann Rheum Dis 2008;67:1165e9.
  20. Ding C, Cicuttini F, Jones G. How important is MRI for detecting early osteoarthritis? Nat Clin Pract Rheumatol 2008;4:4e5.
  21. Ding C, Parameswaran V, Udayan R, Burgess J, Jones G. Circu- lating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab 2008;93:1952e8.
  22. Jones G, Ding C, Scott F, Glisson M, Cicuttini F. Early radio- graphic osteoarthritis is associated with substantial changes in cartilage volume and tibial bone surface area in both males and females. Osteoarthritis Cartilage 2004;12:169e74.
  23. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833e40.
  24. Jones G, Glisson M, Hynes K, Cicuttini F. Sex and site differ- ences in cartilage development: a possible explanation for variations in knee osteoarthritis in later life. Arthritis Rheum 2000;43:2543e9.
  25. Sanchez C, Gabay O, Salvat C, Henrotin YE, Berenbaum F. Mechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts. Osteoarthritis Cartilage 2009;17:473e81.
  26. Distel E, Cadoudal T, Durant S, Poignard A, Chevalier X, Benelli C. The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor. Arthritis Rheum 2009;60:3374e7.
  27. Ding C, Jones G. Anti-interleukin-6 receptor antibody treat- ment in inflammatory autoimmune diseases. Rev Recent Clin Trials 2006;1:193e200.
  28. Brenner SS, Klotz U, Alscher DM, Mais A, Lauer G, Schweer H, et al. Osteoarthritis of the kneeeclinical assessments and inflammatory markers. Osteoarthritis Cartilage 2004;12: 469e75.
  29. Otterness IG, Weiner E, Swindell AC, Zimmerer RO, Ionescu M, Poole AR. An analysis of 14 molecular markers for monitoring osteoarthritis. Relationship of the markers to clinical end- points. Osteoarthritis Cartilage 2001;9:224e31.
  30. Penninx BW, Abbas H, Ambrosius W, Nicklas BJ, Davis C, Messier SP, et al. Inflammatory markers and physical function among older adults with knee osteoarthritis. J Rheumatol 2004;31:2027e31.
  31. Sakao K, Takahashi KA, Mazda O, Arai Y, Tonomura H, Inoue A, et al. Enhanced expression of interleukin-6, matrix metal- loproteinase-13, and receptor activator of NF-kappaB ligand in cells derived from osteoarthritic subchondral bone. J Orthop Sci 2008;13:202e10.
  32. Cicuttini FM, Jones G, Forbes A, Wluka AE. Rate of cartilage loss at two years predicts subsequent total knee arthroplasty: a prospective study. Ann Rheum Dis 2004;63:1124e7.
  33. Amin AR. Regulation of tumor necrosis factor-alpha and tumor necrosis factor converting enzyme in human osteoarthritis. Osteoarthritis Cartilage 1999;7:392e4.
  34. Riyazi N, Slagboom E, de Craen AJ, Meulenbelt I, Houwing- Duistermaat JJ, Kroon HM, et al. Association of the risk of osteoarthritis with high innate production of interleukin- 1beta and low innate production of interleukin-10 ex vivo, upon lipopolysaccharide stimulation. Arthritis Rheum 2005;52:1443e50.
  35. Ding C, Martel-Pelletier J, Pelletier JP, Abram F, Raynauld JP, Cicuttini F, et al. Two-year prospective longitudinal study exploring the factors associated with change in femoral cartilage volume in a cohort largely without knee radiographic osteoarthritis. Osteoarthritis Cartilage 2008;16:443e9.
  36. Engstrom G, Gerhardsson de Verdier M, Rollof J, Nilsson PM, Lohmander LS. C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population- based cohort study. Osteoarthritis Cartilage 2009;17:168e73.

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Authors
Stannus, O., Jones, G., Cicuttini, F., Parameswaran, V., Quinn, S., Burgess, J., & Ding, C.
Affiliations
  • University of Tasmania (AU)
  • Monash University (AU)
  • Royal Hobart Hospital (AU)
Corresponding author
Ding, C.
ORCID
Venue
Osteoarthritis and Cartilage
Publisher
Elsevier BV
Published
2010-11
Volume
18
Issue
11
Pages
1441-1447
ISSN
1063-4584 (ISSN-L)
DOI
10.1016/j.joca.2010.08.016
OpenAlex
W2021234773
Cited by
510
References
0
Citations by year
2026: 28 · 2025: 32 · 2024: 39 · 2023: 35 · 2022: 50 · 2021: 53 · 2020: 45 · 2019: 28 · 2018: 33 · 2017: 30 · 2016: 23 · 2015: 43 · 2014: 29 · 2013: 13 · 2012: 16
FWCI
8.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Osteoarthritis and Cartilage (publishedVersion)
  • PubMed (publishedVersion)
  • eCite Digital Repository (University of Tasmania) (submittedVersion)
  • Flinders Academic Commons (Flinders University) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Arthritis Foundation of Australia
  • University of Tasmania
  • Tasmanian Community Fund
  • Medical Research Council
  • National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Surgery › Hip disorders and treatments
Keywords
knee osteoarthritis, interleukin-6, TNF-α, inflammatory cytokines, joint space narrowing, older adults, cartilage volume
MeSH terms
Aged, Cartilage, Articular, Female, Humans, Knee Joint, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Pain Measurement, Radiography, Tumor Necrosis Factor-alpha, Biomarkers, Interleukin-6, Multivariate Analysis, Osteoarthritis, Knee

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