Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis.
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.
Rooney
T
T
Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin 4, Republic of Ireland. rooneyterence@hotmail.com
Murphy
E
E
Benito
M
M
Roux-Lombard
P
P
FitzGerald
O
O
Dayer
J-M
JM
Bresnihan
B
B
D000208:Acute Disease; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology*; D015535:Arthritis, Psoriatic / Q000276:immunology; D016918:Arthritis, Reactive / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020382:Interleukin-18 / Q000032:analysis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology; D000091402:Prohibitins; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000276:immunology*
D018501:Antirheumatic Agents; D015415:Biomarkers; D020382:Interleukin-18; C000717331:PHB2 protein, human; D000091402:Prohibitins; D002097:C-Reactive Protein