Amelioration of established collagen induced arthritis by systemic IL-10 gene delivery

A novel formulation of cationic liposomes containing the novel cytofectin A CHx was used for delivery of an antiinflammatory cytokine gene, IL-10, to m ice with established collagen induced arthritis. A single intraperitoneal i njection of human IL-10 expression plasmid complexed with liposomes 2 to 4 days after the onset of arthritis was sufficient to give significant and pr olonged amelioration of arthritis for 30 days. Preliminary experiments sugg ested that the therapeutic effect was IL-10 dose-dependent. The distributio n of the human IL-10 DNA after injection was widespread, including the infl amed paws. Human IL-10 mRNA was also detected in the paws 24 h after inject ion. IL-10 protein was below the level of defection in paws and serum but w as defected in some tissues up to 10 days after injection. The target cell of transfection was demonstrated to be the macrophage. These results sugges t that systemic therapy with plasmid DNA complexed with cationic liposomes merits further development as an alternative method for antiinflammatory tr eatment of arthritis.