Adenoviral transfer of the viral IL-10 gene periarticularly to mouse paws suppresses development of collagen-induced arthritis in both injected and uninjected paws

Gene therapy is a promising new approach in the treatment of rheumatoid art hritis. Gene delivery to diseased joints offers the prospect of achieving h igh, local concentrations of a therapeutic gene product in a sustained mann er, while minimizing exposure of nontarget organs. We report that a single administration of a modified adenovirus encoding the Epstein-Barr-derived h omologue of IL-10 can suppress the development of disease for extended peri ods of time when injected locally within the periarticular tissue surroundi ng the ankle joints of mice with collagen type II-induced arthritis. Furthe rmore, we show that injection of an adenoviral vector carrying the IL-10 ge ne into a single paw can suppress development of arthritis in other, noninj ected paws of the same individual. The systemic protection resulting from l ocal gene therapy occurred in the absence of detectable levels of viral IL- 10 in the serum. Circulating Ab levels to heterologous collagen were unaffe cted; however, treatment with viral IL-10 significantly suppressed the deve lopment of Abs to autologous mouse type II collagen. Thus, the treatment of a single joint by local delivery of the VIL-10 gene may protect multiple j oints of the same individual while avoiding deleterious side effects often associated with systemic therapy.