Macrophage-derived cytokine and nuclear factor kappa B p65 expression in synovial membrane and skin of patients with psoriatic arthritis

Objective. Monocyte-derived cytokines are important mediators in synovitis and represent novel therapeutic targets, This study was undertaken to analy ze their expression in synovial membrane (SM) of patients with psoriatic ar thritis (PsA) compared with that in skin of patients with Psii and (SM) of patients with rheumatoid arthritis (RA). Methods. Multiple synovial biopsy samples (24 from patients with PsA 20 fro m patients with RA 5 from patients with osteoarthritis [OA]) and skin biops y samples (lesional and perilesional skin from 25 PsA patients) were obtain ed, Standard leukocyte antigens, cytokines (tumor necrosis factor alpha [TN F alpha], interleukin-1 alpha [IL-1 alpha], IL-1 beta, IL-15, and IL-10) an d the transcription factor nuclear factor kappa B (NF-kappa B; active p65 s ubunit) were localized and quantified immunohistochemically by light micros copy and digital image analysis, Results. Sublining cellular infiltration, lymphoid aggregation, and vascula rity were similar in PsA and Ri SM, Lining layer thickness was greater in R A SM associated with more CD68+ macrophages, In PsA SM, TNF alpha, IL-1 alp ha; IL-1 beta, IL-15, and IL-10 were primarily localized to lining layer an d perivascular macrophages, as were cells expressing the active subunit of NF-KB (p65), TNF alpha, IL-1 beta, and IL-15 expression in PsA lining laver was less than that in Ri lining Iq er, likely reflecting lower macrophage numbers. in sublining areas, levels of TNF alpha and IL-15 were loner in Ps A patients than in Ri patients, whereas IL-1 alpha and IL-1 beta expression was equivalent, IL-10 was identified at similar levels in RA and PsA SM li ning layer and sublining, Expression of NF-kappa B (p65) was equal in linin g layer from both patient groups, but lower in PsA than RA sublining. Histo logic findings did not correlate with clinical parameters of disease. Cytok ine expression in skin did not correlate directly with that in SM. Cytokine expression was greater in PsA and Ri SM than in OA SM. Conclusion. This study shows, for the first time, that monocyte derived cyt okines are found in PsA SR I and demonstrates the relative paucity of the a ntiinflammatory cytokine IL-10 in PsA skin and SM. Significant divergence f rom Ri SM expression was observed, despite similar clinical and demographic features in the 2 patient groups.