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Innate production of Tumor Necrosis Factor-α and Interleukin-10 is associated with radiological progression of knee osteoarthritis.
  1. Stella A Botha-Scheepers (s.a.scheepers{at}lumc.nl)
  1. Leiden University Medical Center, Netherlands
    1. Iain Watt (i.watt{at}lumc.nl)
    1. Leiden University Medical Center, Netherlands
      1. Eline Slagboom (p.slagboom{at}lumc.nl)
      1. Leiden University Medical Center, Netherlands
        1. Anton JM de Craen
        1. Leiden University Medical Center, Netherlands
          1. Ingrid Meulenbelt
          1. Leiden University Medical Center, Netherlands
            1. Frits R Rosendaal
            1. Leiden University Medical Center, Netherlands
              1. Ferdinand C Breedveld
              1. Leiden University Medical Center, Netherlands
                1. Tom WJ Huizinga
                1. Leiden University Medical Center, Netherlands
                  1. Margreet Kloppenburg
                  1. Leiden University Medical Center, Netherlands

                    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 knee OA patients (n=89) were included. Standardised posteroanterior knee radiographs were obtained at baseline and after 24 months. Medial and lateral tibiofemoral joint space narrowing (JSN) were graded with the Altman atlas. Radiological progression was defined as an increase of at least 1 score in JSN total scores. Whole-blood samples were stimulated with lipopolysaccharide (LPS) (10 ng/ml). Relative risks (RR) with 95% confidence intervals (CI95) of OA progression in relation to quartiles of innate ex vivo production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (Ra) and IL-10 were calculated.

                    Results: Progression of JSN was present in 29 (33.7%) of 86 followed patients after two years. Patients in the highest quartile of TNF-α production had a 6-fold increased risk of JSN progression (age, sex and body mass index adjusted RR 6.1, CI95 1.4-9.8) and patients in the highest quartile of IL-10 production had a 4-fold increased risk of JSN progression (age, sex and body mass index adjusted RR 4.3, CI95 1.7-6.2), both in comparison with those patients in the lowest quartile. No significant associations were found between variations in IL-1β and IL-1Ra production and JSN progression.

                    Conclusion: The innate capacity to produce TNF-α and IL-10 upon LPS stimulation is associated with radiological progression of knee OA, even over a relative short follow-up period of two years.

                    • Tumor Necrosis Factor-alpha
                    • innate ex vivo cytokine production
                    • interleukin-10
                    • knee osteoarthritis
                    • progression

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