PMID- 15476228
OWN - NLM
STAT- MEDLINE
DCOM- 20041130
LR  - 20220331
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 50
IP  - 10
DP  - 2004 Oct
TI  - Reduction of synovial sublining layer inflammation and proinflammatory cytokine 
      expression in psoriatic arthritis treated with methotrexate.
PG  - 3286-95
AB  - OBJECTIVE: Methotrexate is one of the most commonly used disease-modifying 
      antirheumatic drugs in the management of psoriatic arthritis (PsA). Despite the 
      differences between the inflammation in PsA and rheumatoid arthritis (RA), the 
      effects of methotrexate on the synovium have been described solely in RA. In this 
      study, we sought to determine the effects of methotrexate on the inflammatory 
      infiltrate and on cytokine and metalloproteinase gene expression in the synovium 
      of PsA patients. METHODS: Ten patients with PsA (median duration 18 months) 
      underwent arthroscopy and synovial biopsy of an inflamed knee before and after 
      clinical improvement induced by methotrexate. Immunohistologic analysis was 
      performed using antibodies to CD3, CD4, CD8, CD68, factor VIII, vascular cell 
      adhesion molecule, E-selectin, and intercellular adhesion molecule (ICAM). Matrix 
      metalloproteinase 3 (MMP-3) and tissue inhibitor of metalloproteinases 1 (TIMP-1) 
      messenger RNA (mRNA) were quantified by competitive reverse 
      transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha (IL-1alpha), 
      IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, 
      interferon-gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) mRNA 
      expression was quantified by real-time PCR. RESULTS: Patients received a median 
      methotrexate dosage of 13.75 mg/week (range 7.5-15) for a median of 11.5 months 
      (range 7-14 months). The Ritchie Articular Index, swollen joint count, and 
      Disease Activity Score were significantly reduced. There was a decrease in all 
      immunohistologic staining, although this was statistically significant only for 
      CD3, CD4, CD8, CD68, E-selectin, and ICAM. Despite clinical improvement in all 
      patients, there was a residual T cell infiltrate in all synovial biopsy tissues. 
      The synovial lining layer thickness, but not hypervascularity, was significantly 
      reduced. There was also a significant reduction in MMP-3, but not TIMP-1, 
      expression. Before treatment, PsA synovium was characterized by a predominant 
      expression of the proinflammatory cytokines IL-15, IFNgamma, IL-1beta, and 
      TNFalpha and the antiinflammatory cytokine IL-10. Methotrexate reduced synovial 
      IL-1alpha, IL-1beta, IL-8, IL-10, IL-15, IFNgamma, and TNFalpha mRNA expression, 
      but the effect was significant only for IL-8. CONCLUSION: Methotrexate produced a 
      clinical response in PsA by reducing, but not abolishing, the inflammatory 
      infiltrate, adhesion molecule expression, and MMP-3 and proinflammatory cytokine 
      gene expression, particularly IL-8, in the synovium. Methotrexate did not reduce 
      hypervascularity, which is a prominent differentiating feature of PsA synovium.
CI  - Copyright 2004 American College of Rheumatology
FAU - Kane, David
AU  - Kane D
AD  - St. Vincent's University Hospital, Dublin, Ireland. d.j.kane@ncl.ac.uk
FAU - Gogarty, Martina
AU  - Gogarty M
FAU - O'leary, John
AU  - O'leary J
FAU - Silva, Ivan
AU  - Silva I
FAU - Bermingham, Niamh
AU  - Bermingham N
FAU - Bresnihan, Barry
AU  - Bresnihan B
FAU - Fitzgerald, Oliver
AU  - Fitzgerald O
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.- (Metalloproteases)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Psoriatic/*drug therapy/*metabolism
MH  - Arthroscopy
MH  - Cytokines/genetics
MH  - Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - Inflammation/pathology
MH  - Knee
MH  - Metalloproteases/genetics
MH  - Methotrexate/administration & dosage/pharmacology/*therapeutic use
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Synovial Membrane/drug effects/*pathology
EDAT- 2004/10/12 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/10/12 09:00
PHST- 2004/10/12 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/12 09:00 [entrez]
AID - 10.1002/art.20518 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2004 Oct;50(10):3286-95. doi: 10.1002/art.20518.