Recently, it has been demonstrated that
oxygen free radicals have an important role as a signaling messenger in the development of
inflammation and osteoclastogenesis, suggesting the implication of
oxygen free radicals in the pathogenesis of
arthritis. The aim of this study was to examine the potential of a strong
free-radical scavenger, water-soluble
fullerene (C60), as a
protective agent against
synovitis in
arthritis, both in vitro and in vivo. In the presence or absence of C60 (0.1, 1.0, 10.0 muM), human synovial fibroblasts, synovial infiltrating lymphocytes or macrophages were incubated with
tumor necrosis factor-alpha (
TNF-alpha) (10.0 ng/mL), and the production of proinflammatory
cytokines by the individual cells were analyzed. C60 significantly suppressed the
TNF-alpha-induced production of proinflammatory
cytokines in synovial fibroblasts, synovial infiltrating lymphocytes and macrophages in vitro. Adjuvant induced arthritic rats were used as an animal model of
arthritis. Rats were divided into two subgroups: control and treatment with C60 at 10.0 muM. The left ankle joint was injected intraarticularly with water-soluble C60 (20 mul) in the C60-treated group, while, as a control, the left ankle joint in the control rats received
phosphate-buffered saline (20 mul), once weekly for eight weeks. Ankle joint tissues were prepared for histological analysis. In adjuvant-induced arthritic rats, intra-articular treatment with C60 in vivo reduced
synovitis and alleviated
bone resorption and destruction in the joints, while control ankle joints showed progression of
synovitis and joint destruction with time. These findings indicate that C60 is a potential therapeutic agent for inhibition of
arthritis.