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Innate production of tumour necrosis factor α and interleukin 10 is associated with radiological progression of knee osteoarthritis
  1. S Botha-Scheepers1,
  2. I Watt2,
  3. E Slagboom3,
  4. A J M de Craen3,
  5. I Meulenbelt4,
  6. F R Rosendaal5,
  7. F C Breedveld,
  8. T W J Huizinga1,
  9. M Kloppenburg1
  1. 1
    Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
  2. 2
    Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands
  3. 3
    Department of Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands
  4. 4
    Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
  5. 5
    Department of Clinical Epidemiology and Haematology, Leiden University Medical Centre, Leiden, The Netherlands
  1. S Botha-Scheepers, Leiden University Medical Centre, Department of Rheumatology, C01-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands; S.A.Scheepers{at}lumc.nl

Abstract

Objectives: Inflammation may contribute to progression of knee osteoarthritis (OA). Therefore, we investigated whether innate differences in the inflammatory response regarding cytokine production were associated with radiological progression of knee OA.

Methods: Symptomatic patients with knee OA (n = 89) were included. Standardised posteroanterior knee radiographs were obtained at baseline and after 24 months. Medial and lateral tibiofemoral joint space narrowing (JSN) was graded with the Altman atlas. Radiological progression was defined as an increase of at least one score in JSN total scores. Whole blood samples were stimulated with lipopolysaccharide (LPS) (10 ng/ml). Relative risks (RR) with 95% CIs of OA progression in relation to quartiles of innate ex vivo production of interleukin (IL)1β, tumour necrosis factor (TNF)α, IL1 receptor antagonist (Ra) and IL10 were calculated.

Results: Progression of JSN was present in 29 (33.7%) of 86 followed patients after 2 years. Patients in the highest quartile of TNFα production had a sixfold increased risk of JSN progression (age, sex and body mass index adjusted RR 6.1, 95% CI 1.4 to 9.8) and patients in the highest quartile of IL10 production had a fourfold increased risk of JSN progression (age, sex and body mass index adjusted RR 4.3, 95% CI 1.7 to 6.2), both in comparison with those patients in the lowest quartile. No significant associations were found between variations in IL1β and IL1Ra production and JSN progression.

Conclusion: The innate capacity to produce TNFα and IL10 upon LPS stimulation is associated with radiological progression of knee OA, even over a relatively short follow-up period of 2 years.

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Footnotes

  • Funding: The Genetics, Arthrosis and Progression (GARP) study cohort, whose members took part in the present work, was partly sponsored by Pfizer Inc., Groton, CT, USA. Pfizer was not involved in the present study and had no role in obtaining, analysing and interpreting data on cytokine profiles.

  • Competing interests: None declared.

  • Ethics approval: The Genetics, Arthrosis and Progression (GARP) study was approved by the Medical Ethics Committee of the Leiden University Medical Center.