Non-steroidal anti-oestrogens inhibit the differentiation of synovial macrophages into dendritic cells

Abstract

Background. Dendritic cells (DC) have been suggested to play an important role in the pathogenesis of rheumatoid arthritis (RA). Agents that inhibit DC differentiation and function may have a therapeutic value in the treatment of RA. Objective. To examine the effect of the non-steroidal anti-oestrogens toremifene and tamoxifen on the differentiation of synovial fluid (SF) macrophages into DC. Methods. SF macrophages from patients with RA were cultured with interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) in the presence or absence of anti-oestrogens. The expression of cell surface markers on SF antigen-presenting cells (APC) was studied by flow cytometry. The capacity of SF APC to stimulate allogeneic T cells was studied using the mixed lymphocyte reaction. The production of tumour necrosis factor-α, IL-10 and transforming growth factor-β1 was studied using ELISA. Results. Anti-oestrogens inhibited the differentiation of SF macrophages into DC and the capacity of SF macrophage-derived DC to stimulate allogeneic T cells. Conclusions. By inhibiting the differentiation of SF macrophages into DC, non-steroidal anti-oestrogens may have beneficial effects in RA.