Suppressive effects of a novel compound on interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis in rats

Abstract

The immunosuppressive effect of ethyl O-(N-(pcarboxyphenyl)-carbamoyl)-mycophenolate(CAM) was examined in interphotoreceptor retinoid-binding protein (IRBP)-induced experimental autoimmune uveoretinitis (EAU) in rats. Lewis rats immunized with bovine IRBP were treated with various oral doses of CAM postimmunization. The degree of inflammation was assessed clinically each day and histologically on day 14 or day 20. Production of various cytokines and IRBP-specific antibody, as well as IRBP-specific proliferation response, was assessed. Complete inhibition of EAU in rats, both by clinical and histologic criteria, was achieved with 50 mg/kg CAM when administered daily for 14 days following IRBP immunization. Partial inhibition was observed at lesser doses of CAM. This CAM-mediated response was accompanied by diminished production of cytokines interleukin-2, interferon-γ and tumor necrosis factor-α, as well as a reduction in IRBP-specific antibody production. Furthermore, administration of CAM either in the induction phase only (days 0–7) or in the effector phase only (days 9 or 11 to day 20) was also capable of suppressing EAU, as assessed histopathologically on day 20. We conclude that CAM is effective in suppressing EAU in rats and its mechanism of action appears to involve modulation of T cell function.

Keywords

• cytokine
• experimental autoimmune uveoretinitis
• immunosuppression
• interphotoreceptor retinoid-binding protein
• mycophenolic acid