Alleviation of collagen-induced arthritis through cytokine-modulatory activity of Brazilian propolis AF-08 in mice

Brazilian propolis AF-08 as a dietary supplement has been shown to be effective in alleviating symptoms of herpes simplex virus and respiratory syncytial virus infection in mice. The alleviation was associated with the modification of immunological activity by AF-08 as a cytokine regulator. The immunomodulatory activity of AF-08 was suggested to contribute to the severity of symptoms and pathogenesis in cytokine-mediated diseases. In this study, we investigated the effectiveness of AF-08 as a potential cytokine modulator in alleviating autoimmune diseases. The efficacy and cytokine-modulatory activity of AF-08 were examined in collagen-induced arthritis (CIA) in mice. Mice were immunized with type II collagen. AF-08 at 0, 30, or 100 mg/kg was administered orally to the immunized mice once daily for three weeks before and/or three times daily for two weeks after the onset of CIA. The development of arthritis of the paws and inflammatory cytokine levels in serum were examined. AF-08 at 100 mg/kg significantly reduced the incidence and severity of CIA prophylactically and therapeutically and reduced the rise of systemic interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α levels in the early phase of CIA. In the early phase of CIA, the reduction of inflammatory cytokine levels by AF-08 correlated with the amelioration of symptoms of CIA. AF-08 might inhibit the initiation of cytokine-mediated disease rather than suppressing disease progression without toxicity. AF-08 was confirmed to possess cytokine-modulatory activity in vivo. It is possible that AF-08 is a potential prophylactic and therapeutic agent for autoimmune diseases.