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We investigated the immunosuppressive effect of FK 506 on adjuvant arthritis in rats as an experimental model of rheumatoid arthritis.FK 506 was intramuscularly administered at a dose of 0.32 mg/kg/day from day 0 to day 28 after adjuvant injection. The severity of arthritis was evaluated by macroscopic score graded from 0 to 4 for each limb and histopathological examination of joints stained with hematoxylin and eosin. We also examined the expression of fibroblast growth factor (FGF) -1 and tyrosine phosphorylated proteins (phosphotyrosine, P-Tyr) in the inflamed synovia by immunoperoxidase staining.FK 506 macroscopically prevented the development of arthritis and suppressed the proliferation of synovial tissues, the infiltration of inflammatory mononuclear cells and the destruction of bone and cartilage when compared with the control group. The expression of FGF-1 and P-Tyr of synovial sections was suppressed by treatment with FK 506. The intensity of immunostaining observed within synovial lining cells, sublining stromal fibroblast-like cells and cartilage chondrocytes decreased.These findings suggest that FK 506 is a useful drug for the treatment of rheumatoid arthritis.

Effect of FK506 on adjuvant arthritis in rats: Studies on the expression of fibroblast growth factor-1 and tyrosine phosphorylated proteins.