Effects of tumor necrosis factor-alpha, interleukin 1 beta, and activated peripheral blood mononuclear cells on the expression of adhesion molecules and recruitment of leukocytes in rheumatoid synovial xenografts in SCID mice

Objective. To examine expression of adhesion molecules within human synovia l xenografts in vivo after injection of human cytokines or peripheral blood mononuclear cells (PBMC). Methods, Rheumatoid synovium was transplanted into subcutaneous pouches in the ears of severe combined immunodeficient (SCID) mice. Tumor necrosis fac tor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), or PBMC were injecte d into the xenografts. The grafts were assessed by immunohistochemistry and quantitative video image analysis. Results. TNF-alpha, IL-1 beta, and concanavalin A activated PBMC increased the expression of vascular cellular adhesion molecule I and intercellular a dhesion molecule I significantly on vessels and nonvascular synovial cells compared with injection of medium only. Vascular expression of E-selectin, but not of MHC Class II, was also increased. These stimuli also induced the migration of murine leukocytes into the xenografts. Conclusion. Rheumatoid synovial xenografts in SCID mice respond by upregula tion of adhesion molecule expression when challenged in vivo with proinflam matory cytokines or activated PBMC.