INHIBITION OF INTERLEUKIN-1-INDUCED EFFECTS IN SYNOVIOCYTES TRANSDUCED WITH THE HUMAN IL-1 RECEPTOR ANTAGONIST CDNA USING AN ADENOVIRAL VECTOR

In this report, we present data showing that a recombinant adenoviral vector (Ad.RSVIL-1ra) containing the cDNA for human interleukin-1 rece ptor antagonist protein (IL-1ra) can genetically modify synoviocytes b oth in vitro and in vivo. Human synoviocytes infected with Ad.RSVIL-1r a in vitro expressed and secreted high levels of human IL-1ra that wer e detected by ELISA of tissue culture supernatants. New Zealand White rabbits that received intra-articular injections of Ad.RSVIL-1ra expre ssed transgenic IL-1ra in synoviocytes, and secretion was detected for at least 4 weeks post-infection. Further, biological activity of the transgenic IL-1ra was demonstrated by its ability to inhibit IL-1-indu ced prostaglandin E(2) (PGE(2)) synthesis in vitro and IL-1-induced gl ycosaminoglycan (GAG) degradation in vivo. These data demonstrate that recombinant adenoviral vectors can mediate the intra-articular expres sion of anti-inflammatory proteins and may be a reasonable method to d eliver therapeutically relevant proteins for the regional treatment of synovial inflammation.