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Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate.
Arthritis Rheum. 2004 Oct; 50(10):3286-95.AR

Abstract

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.

Authors+Show Affiliations

St. Vincent's University Hospital, Dublin, Ireland. d.j.kane@ncl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15476228

Citation

Kane, David, et al. "Reduction of Synovial Sublining Layer Inflammation and Proinflammatory Cytokine Expression in Psoriatic Arthritis Treated With Methotrexate." Arthritis and Rheumatism, vol. 50, no. 10, 2004, pp. 3286-95.
Kane D, Gogarty M, O'leary J, et al. Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate. Arthritis Rheum. 2004;50(10):3286-95.
Kane, D., Gogarty, M., O'leary, J., Silva, I., Bermingham, N., Bresnihan, B., & Fitzgerald, O. (2004). Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate. Arthritis and Rheumatism, 50(10), 3286-95.
Kane D, et al. Reduction of Synovial Sublining Layer Inflammation and Proinflammatory Cytokine Expression in Psoriatic Arthritis Treated With Methotrexate. Arthritis Rheum. 2004;50(10):3286-95. PubMed PMID: 15476228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate. AU - Kane,David, AU - Gogarty,Martina, AU - O'leary,John, AU - Silva,Ivan, AU - Bermingham,Niamh, AU - Bresnihan,Barry, AU - Fitzgerald,Oliver, PY - 2004/10/12/pubmed PY - 2004/12/16/medline PY - 2004/10/12/entrez SP - 3286 EP - 95 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 50 IS - 10 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15476228/Reduction_of_synovial_sublining_layer_inflammation_and_proinflammatory_cytokine_expression_in_psoriatic_arthritis_treated_with_methotrexate_ L2 - https://doi.org/10.1002/art.20518 DB - PRIME DP - Unbound Medicine ER -