INTERLEUKIN-4 INCREASES HUMAN SYNOVIAL CELL EXPRESSION OF VCAM-1 AND T-CELL BINDING

Objective-The effects were studied of interleukin 4 (IL-4) on T cell-s ynovial cell adhesion and on the expression of adhesion molecules on t he surface of synovial fibroblast-like cells. Methods-The adhesion of T cells toward the synovial cells were measured by (51)chromium-labell ed adhesion assay. The expression of adhesion molecules on synovial ce lls were analysed by flowcytometry. Results-Stimulation of synovial ce lls with IL-4 increased T cell-synovial cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VC AM-1 on the surface of synovial cells, but not the expression of ICAM- 1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on t he expression of ICAM-1 or VCAM-1 on the surface of synovial cells. Th e increased adhesion of T cells to IL-4 stimulated synovial cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA -4 alpha and anti-VCAM-1 antibodies blocked completely T-cell binding to IL-4 stimulated synovial cells. Conclusions-These results suggest t hat the increased adhesion of T cells to IL-4-stimulated synovial cell s is mediated by VLA-4/VCAM-1 pathway.