FK506 inhibits prostaglandin E2 production from synovial cells by suppressing peripheral blood mononuclear cells

FK506, an immunosuppressive drug for T cells, reduces pain in patients with rheumatoid arthritis. However, the mechanism for pain reduction remains uncharacterized. In this study, we investigated the effect of FK506 on prostaglandin E2 (PGE2) production from synovial cells in vitro. Human synovial cells were cultured with supernatant from peripheral blood mononuclear cells (PBMC) stimulated with anti-CD3 plus anti-CD28 antibodies. Cultured synovial cells with PBMC supernatant produced a high amount of PGE2 and FK506 inhibited PGE2 induction from synovial cells. Culture supernatant contained interleukin-1β (IL-1β) and TNFα, and FK506 suppressed both in PBMC supernatant. Anti-IL-1β neutralizing antibody, but not anti-TNFα neutralizing antibody, completely inhibited PGE2 induction by PBMC supernatant. These results suggest that FK506 suppresses inflammation by inhibiting PGE2 production from synovial cells through suppression of IL-1β production from leukocytes.