DIRECT ADENOVIRUS-MEDIATED GENE-TRANSFER OF INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR-ALPHA SOLUBLE RECEPTORS TO RABBIT KNEES WITH EXPERIMENTAL ARTHRITIS HAS LOCAL AND DISTAL ANTIARTHRITIC EFFECTS

Adenoviral vectors were used to deliver genes encoding a soluble inter leukin 1 (IL-1)-type I receptor-IgG fusion protein and/or a soluble ty pe I tumor necrosis factor alpha (TNF alpha) receptor-IgG fusion prote in directly to the knees of rabbits with antigen-induced arthritis. Wh en tested individually, knees receiving the soluble IL-1 receptor had significantly reduced cartilage matrix degradation and white blood cel l infiltration into the joint space. Delivery of the soluble TNF alpha receptor was less effective, having only a moderate effect on white b lood cell infiltration and no effect on cartilage breakdown. When both soluble receptors were used together, there was a greater inhibition of white blood cell infiltration and cartilage breakdown with a consid erable reduction of synovitis. Interestingly, anti-arthritic effects w ere also seen in contralateral control knees receiving only a marker g ene, suggesting that sustained local inhibition of disease activity in one joint mag confer an anti-arthritic effect on other joints. These results suggest that local intra-articular gene transfer could be used to treat systemic polyarticular arthritides.