Inhibition of Adjuvant Arthritis in Rats by Electroporation with lnterleukin-1 Receptor Antagonist

To assess the protective effects of the cytokine inhibitor interleukin-1 receptor antagonist (IL-1ra) on gene induction, an electroporation technique to treat adjuvant-induced arthritis (AIA) in rats was established, and its advantage was estimated in the present study. Electroporation with human IL-1ra was performed in Lewis rats before and after induction of AIA. Local inflammation was evaluated by monitoring hind paw swelling, whereas histological evaluations were performed using paraffin embedded sections of hind paw specimens stained with hematoxylin and eosin. In addition, serum IL-1 beta levels were analyzed using an enzyme-linked immunosorbent assay. Induction of IL-1ra by our electroporation method inhibited systematic body weight loss and enhancement of local inflammation after intradermal injection of heat-killed Mycobacterium tuberculosis. Notably, IL-1ra electroporation reduced paw swelling, inflammation, and bone erosion scores in embedded sections and serum IL-1 beta levels induced in AIA rats. The IL-1ra gene induction using the present electroporation technique inhibited local and systematic inflammation in AIA rats. These results indicate that this method may represent a novel pharmacotherapy strategy for arthritis.