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Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis.
Arthritis Rheum. 2000 Jun; 43(6):1244-56.AR

Abstract

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 PsA 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 [TNFalpha], interleukin-1apha [IL-1alpha], IL-1beta, IL-15, and IL-10) and the transcription factor nuclear factor KB (NF-kappaB; 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 RA SM. Lining layer thickness was greater in RA SM, associated with more CD68+ macrophages. In PsA SM, TNFalpha, IL-1alpha, IL-1beta, IL-15, and IL-10 were primarily localized to lining layer and perivascular macrophages, as were cells expressing the active subunit of NF-kappaB (p65). TNFalpha, IL-1p, and IL-15 expression in PsA lining layer was less than that in RA lining layer, likely reflecting lower macrophage numbers. In sublining areas, levels of TNFalpha and IL-15 were lower in PsA patients than in RA patients, whereas IL-lalpha and IL-1beta expression was equivalent. IL-10 was identified at similar levels in RA and PsA SM lining layer and sublining. Expression of NF-kappaB (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 RA SM than in OA SM.

CONCLUSION

This study shows, for the first time, that monocyte-derived cytokines are found in PsA SM and demonstrates the relative paucity of the antiinflammatory cytokine IL-10 in PsA skin and SM. Significant divergence from RA SM expression was observed, despite similar clinical and demographic features in the 2 patient groups.

Authors+Show Affiliations

University of Glasgow, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10857783

Citation

Danning, C L., et al. "Macrophage-derived Cytokine and Nuclear Factor kappaB P65 Expression in Synovial Membrane and Skin of Patients With Psoriatic Arthritis." Arthritis and Rheumatism, vol. 43, no. 6, 2000, pp. 1244-56.
Danning CL, Illei GG, Hitchon C, et al. Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis. Arthritis Rheum. 2000;43(6):1244-56.
Danning, C. L., Illei, G. G., Hitchon, C., Greer, M. R., Boumpas, D. T., & McInnes, I. B. (2000). Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis. Arthritis and Rheumatism, 43(6), 1244-56.
Danning CL, et al. Macrophage-derived Cytokine and Nuclear Factor kappaB P65 Expression in Synovial Membrane and Skin of Patients With Psoriatic Arthritis. Arthritis Rheum. 2000;43(6):1244-56. PubMed PMID: 10857783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis. AU - Danning,C L, AU - Illei,G G, AU - Hitchon,C, AU - Greer,M R, AU - Boumpas,D T, AU - McInnes,I B, PY - 2000/6/17/pubmed PY - 2000/7/8/medline PY - 2000/6/17/entrez SP - 1244 EP - 56 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 43 IS - 6 N2 - 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 PsA 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 [TNFalpha], interleukin-1apha [IL-1alpha], IL-1beta, IL-15, and IL-10) and the transcription factor nuclear factor KB (NF-kappaB; 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 RA SM. Lining layer thickness was greater in RA SM, associated with more CD68+ macrophages. In PsA SM, TNFalpha, IL-1alpha, IL-1beta, IL-15, and IL-10 were primarily localized to lining layer and perivascular macrophages, as were cells expressing the active subunit of NF-kappaB (p65). TNFalpha, IL-1p, and IL-15 expression in PsA lining layer was less than that in RA lining layer, likely reflecting lower macrophage numbers. In sublining areas, levels of TNFalpha and IL-15 were lower in PsA patients than in RA patients, whereas IL-lalpha and IL-1beta expression was equivalent. IL-10 was identified at similar levels in RA and PsA SM lining layer and sublining. Expression of NF-kappaB (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 RA SM than in OA SM. CONCLUSION: This study shows, for the first time, that monocyte-derived cytokines are found in PsA SM and demonstrates the relative paucity of the antiinflammatory cytokine IL-10 in PsA skin and SM. Significant divergence from RA SM expression was observed, despite similar clinical and demographic features in the 2 patient groups. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10857783/Macrophage_derived_cytokine_and_nuclear_factor_kappaB_p65_expression_in_synovial_membrane_and_skin_of_patients_with_psoriatic_arthritis_ L2 - https://doi.org/10.1002/1529-0131(200006)43:6<1244::AID-ANR7>3.0.CO;2-2 DB - PRIME DP - Unbound Medicine ER -