Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, leading to cartilage and bone destruction. We investigated whether the electrotransfer of IL-4 DNA could regulate the disease progress of murine collagen-induced arthritis (CIA). The maximum serum level of ml L-4 was measured by 340 pg/ml on day I following DNA transfer. The onset of severe CIA and the degree of synovitis and cartilage erosion were significantly reduced in mice treated with IL-4 DNA (P < 0.05). The beneficial effect of IL-4 gene transfer lasted for at least 17 days subsequent to treatment. The expression of IL-1beta was considerably decreased in the paws by IL-4 DNA transfer (P < 0.01). On the contrary, the ratio of TIMP2 to MMP2 significantly increased in the IL-4 DNA-treated group (P < 0.01). These data demonstrated that electroporation-mediated gene transfer could provide a new approach as an IL-4 therapy for autoirninune arthritis. (C) 2004 Elsevier Inc. All rights reserved.