EXTENDED REPORT

Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis

T Rooney¹, E Murphy¹, M Benito¹, P Roux-Lombard², O FitzGerald¹, J-M Dayer² and B Bresnihan¹

¹ Department of Rheumatology, St Vincent’s University Hospital, Dublin, Republic of Ireland
² Division of Immunology and Allergy, University Hospital, Geneva, Switzerland

Correspondence to:
Correspondence to:
Dr T Rooney
Department of Rheumatology, St Vincent’s University Hospital, Elm Park, Dublin 4, Republic of Ireland; rooneyterence{at}hotmail.com

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.

Abbreviations: 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

Keywords: DMARD; arthritis; interleukin-18; synovial tissue

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