Morphometric analysis of synovial membrane blood vessels in rheumatoid arthritis: associations with the immunohistologic features, synovial fluid cytokine levels and the clinical course.

Abstract

The morphologic characteristics of the endothelial cells lining postcapillary venules are cytokine dependent and critical in facilitating the infiltration of mononuclear cells into synovial membrane in rheumatoid arthritis (RA). We determined the relationships between endothelial cell (EC) tallness, mononuclear cell infiltration and synovial fluid levels of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) at different stages of RA. EC tallness was greatest in synovial tissues obtained by needle biopsy of the knee joints from 18 patients with active RA who had never received disease modifying drugs (Group 1) (p = 0.000001 versus controls). EC tallness in tissues obtained from 18 patients with advanced disease undergoing knee arthroplasty (Group 2) was greater than controls (p = 0.001) only when vessels located in focal lymphoid aggregates were considered. Vascular proliferation was noted in both groups. Synovial fluid IL-6 levels were greatest in Group 1. IL-1 beta levels were greatest in Group 2. The total numbers of infiltrating mononuclear cells and the clinical measures of disease activity were similar in both groups. The differences in EC characteristics at different stages of RA suggest changing pathogenic mechanisms as disease progresses. Disease modifying antirheumatic drugs may contribute to the findings observed.