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 E(2) (PGE(2)) 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 PGE(2) and FK506 inhibited PGE(2) induction from synovial cells. Culture supernatant contained interleukin-1beta (IL-1beta) and TNFalpha, and FK506 suppressed both in PBMC supernatant. Anti-IL-1beta neutralizing antibody, but not anti-TNFalpha neutralizing antibody, completely inhibited PGE(2) induction by PBMC supernatant. These results suggest that FK506 suppresses inflammation by inhibiting PGE(2) production from synovial cells through suppression of IL-1beta production from leukocytes.