Direct adenoviral gene transfer of viral IL-10 to rabbit knees with experimental arthritis ameliorates disease in both injected and contralateral control knees

IL-10, a cytokine produced primarily by macrophages, B lymphocytes, and Th2 cells, has both immunostimulatory and immunosuppressive properties. A homo logue of IL-10 encoded by EBV, known as viral IL-10 (vIL-10), is also able to suppress the immune response, but may lack some of the immunostimulatory properties of IL-10. To evaluate the potential of vIL-10 to block the prog ression of rheumatoid arthritis, we have utilized a replication-defective a denovirus vector to deliver the gene encoding vIL-10 to the knee joints of rabbits with Ag-induced arthritis. Intraarticular expression of VIL-10 sign ificantly reduced leukocytosis, cartilage matrix degradation, and levels of endogenous rabbit TNF-alpha, as well as the degree of synovitis, while mai ntaining high levels of cartilage matrix synthesis. Interestingly, an antia rthritic effect was also observed in opposing contralateral control knee jo ints that received only a marker gene. An adenoviral vector carrying the en hanced green fluorescent protein marker gene was used to demonstrate that a morphologically similar subset of cells infected in the injected knee fein t are able to traffic to the uninjected contralateral knee joint. Our resul ts suggest that direct, local intraarticular delivery of the vIL-10 gene ma y have polyarticular therapeutic effects.