Mononuclear cell retention in rheumatoid synovial tissue engrafted in severe combined immunodeficient (SCID) mice is up-regulated by tumour necrosis factor-alpha (TNF-alpha) and mediated through intercellular adhesion molecule-1 (ICAM-1).

The aim of this study was to assess regulation of mononuclear cell (MNC) traffic to human synovial tissue by TNF-alpha and IL-1 and the involvement of ICAM-1 in MNC retention in rheumatoid synovial tissue. Human rheumatoid arthritis synovium was engrafted subcutaneously in 6-8 week-old SCID/CB17 mice. Three weeks later, we injected 20 x 10(6) human peripheral blood mononuclear cells (PBMC) previously labelled with 111indium intraperitoneally into mice containing control or cytokine-injected grafts. Total body scintigraphy was performed 72 h postinjection. The graft was removed and immunochemical analysis carried out to assess ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. In some experiments, mice were treated intravenously with 500 micrograms MoAb anti-ICAM-1 (BIRR-1) or an isotype-matched control MoAb before introduction of MNC. TNF-alpha, but not IL-1 alpha, enhanced MNC retention in the rheumatoid synovial graft 72 h post-injection (graft activity 989 +/- 1227 ct/min per 200 pixels or 3.36 +/- 4.16% of initial injected activity versus 411 +/- 157 ct/min per 200 pixels or 1.13 +/- 0.45% in controls; P < 0.03). TNF-alpha enhanced ICAM-1 expression by synovial cells and endothelial cells, whereas VCAM-1 or E-selectin expression was not enhanced on either cell type. After MoAb treatment of ICAM-1, synovial lymphocyte recruitment of TNF-alpha-treated mice decreased significantly to levels below that of control mice (160 +/- 97 ct/min per 200 pixels, 0.54 +/- 0.33%; P < 0.01). Mononuclear cell retention in rheumatoid synovial tissue engrafted into SCID mice was up-regulated by TNF-alpha and blocked by MoAb to ICAM-1. These results suggest that ICAM-1 is involved in mononuclear cell retention in rheumatoid synovium.