Macrophage-derived cytokine and nuclear factor κB 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 analyze their expression in synovial membrane (SM) of patients with psoriatic arthritis (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 from patients with RA 5 from patients with osteoarthritis [OA]) and skin biopsy samples (lesional and perilesional skin from 25 PsA patients) were obtained, Standard leukocyte antigens, cytokines (tumor necrosis factor alpha [TNF alpha], interleukin-1 alpha [IL-1 alpha], IL-1 beta, IL-15, and IL-10) and the transcription factor nuclear factor kappa B (NF-kappa B; active p65 subunit) were localized and quantified immunohistochemically by light microscopy and digital image analysis, Results. Sublining cellular infiltration, lymphoid aggregation, and vascularity were similar in PsA and Ri SM, Lining layer thickness was greater in RA SM associated with more CD68+ macrophages, In PsA SM, TNF alpha, IL-1 alpha; IL-1 beta, IL-15, and IL-10 were primarily localized to lining layer and 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 PsA 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 lining layer and sublining, Expression of NF-kappa B (p65) was equal in lining layer from both patient groups, but lower in PsA than RA sublining. Histologic findings did not correlate with clinical parameters of disease. Cytokine 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 cytokines are found in PsA SR I and demonstrates the relative paucity of the antiinflammatory cytokine IL-10 in PsA skin and SM. Significant divergence from Ri SM expression was observed, despite similar clinical and demographic features in the 2 patient groups.