Effects of Pyrrolidine Dithiocarbamate, an Nf-κb Inhibitor, on Cytokine Expression and Ocular Inflammation in Experimental Autoimmune Anterior Uveitis

Aims: The aim of this study was to investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor (NF) -icB inhibitor, on cytokine expression and suppression of anterior chamber inflammation in experimental autoimmune anterior uveitis. Uveitis was induced in the Lewis rats with the injection of a melanin-associated antigen into the peritoneum and footpad. At defined time points, cytokine mRNA expressions in the iris and ciliary body were measured by using a semiquantitative polymerase chain-reaction method . Results: We found that interferon-y ( IFN-y) and tumor necrosis factor (TNF)-a mRNA ex- pression peaked during the active phase of uveitis, whereas interleukin (IL)-1O mRNA in - creased during the disease resolution. In a separate experiment, PDTC (100 and 200 mg/kg/day) was administrated intraperitoneally daily after immunization. We found that PDTC (100 and 200 mg/kg/day) effectively suppressed ocular inflammation, as indicated by reduced clinical scores and inflammatory cells infiltration in aqueous humor and the iris and ciliary body. Conclusions: The inhibitory effects of PDTC are mainly resulted from inhibiting the ex- pression of proinflammatory cytokines, TNF-a and IFN-y but augmenting anti-inflammatory cytokines, IL-b expression. These findings suggest that the application of NE-KB inhibitors may be a potential therapeutic method for the treatment of acute anterior uveitis