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Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis
  1. T Rooney1,
  2. E Murphy1,
  3. M Benito1,
  4. P Roux-Lombard2,
  5. O FitzGerald1,
  6. J-M Dayer2,
  7. B Bresnihan1
  1. 1Department of Rheumatology, St Vincent’s University Hospital, Dublin, Republic of Ireland
  2. 2Division of Immunology and Allergy, University Hospital, Geneva, Switzerland
  1. Correspondence to:
    Dr T Rooney
    Department of Rheumatology, St Vincent’s University Hospital, Elm Park, Dublin 4, Republic of Ireland; rooneyterencehotmail.com

Abstract

Objective: To measure synovial tissue interleukin-18 (IL-18) expression in patients with inflammatory arthritis, and to identify associations with serum levels, disease activity, and response to treatment.

Methods: Synovial tissue biopsies and serum samples were obtained from patients with early, active, rheumatoid arthritis (RA) (n = 12), undifferentiated seronegative arthritis (SnA) (n = 9), psoriatic arthritis (PsA) (n = 5), and reactive arthritis (ReA) (n = 2) before and one year after introduction of disease modifying antirheumatic drug (DMARD) treatment. Osteoarthritis (OA) tissues were compared. Tissue IL-18 expression was determined after immunohistochemical staining using a semiquantitative scale. Serum IL-18 was measured by enzyme linked immunosorbent assay.

Results: Before treatment was started, tissue IL-18 expression was increased in each diagnostic group compared with OA (p<0.05). Tissue IL-18 expression was correlated with serum C reactive protein levels (r = 0.53, p = 0.003) but not with serum IL-18. After DMARD treatment, 12 patients (five RA, four SnA, three PsA) were re-evaluated. Decreases in tissue IL-18 expression were observed in eight, although the trend did not reach significance (p = 0.068). Changes in tissue IL-18 expression were correlated with changes in serum IL-18 (r = 0.62, p = 0.041) and C reactive protein (r = 0.72, p = 0.009).

Conclusions: Synovial tissue IL-18 expression was correlated with disease activity in inflammatory arthritis. After treatment, tissue levels changed in parallel with changes in serum IL-18 and with changes in the acute phase response. These observations support a role for IL-18 in the pathophysiology of inflammatory arthritis.

  • DMARD, disease modifying anti-rheumatic drug
  • IL, interleukin
  • OA, osteoarthritis
  • PBMC, peripheral blood mononuclear cells
  • PsA, psoriatic arthritis
  • RA, rheumatoid arthritis
  • ReA, reactive arthritis
  • SnA, undifferentiated seronegative arthritis
  • DMARD
  • arthritis
  • interleukin-18
  • synovial tissue

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