Abstract
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-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 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-1β production from leukocytes.
Published Version
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