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

Ann Rheum Dis. 2004 Nov;63(11):1393-8. doi: 10.1136/ard.2003.016428.

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.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Arthritis / drug therapy*
  • Arthritis / immunology*
  • Arthritis, Psoriatic / immunology
  • Arthritis, Reactive / immunology
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / analysis
  • C-Reactive Protein / analysis
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Interleukin-18 / analysis*
  • Interleukin-18 / blood
  • Male
  • Middle Aged
  • Osteoarthritis / immunology
  • Prohibitins
  • Statistics, Nonparametric
  • Synovial Membrane / immunology*

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Interleukin-18
  • PHB2 protein, human
  • Prohibitins
  • C-Reactive Protein