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Departments of
*
Molecular Genetics and Biochemistry and
Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261;
Megabios, Burlingame, CA 94010; and
§
GenVec, Rockville, MD 20852
IL-10, a cytokine produced primarily by macrophages, B lymphocytes,
and Th2 cells, has both immunostimulatory and immunosuppressive
properties. A homologue 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 progression of rheumatoid arthritis,
we have utilized a replication-defective adenovirus vector to deliver
the gene encoding vIL-10 to the knee joints of rabbits with Ag-induced
arthritis. Intraarticular expression of vIL-10 significantly reduced
leukocytosis, cartilage matrix degradation, and levels of endogenous
rabbit TNF-
, as well as the degree of synovitis, while maintaining
high levels of cartilage matrix synthesis. Interestingly, an
antiarthritic effect was also observed in opposing contralateral
control knee joints that received only a marker gene. An adenoviral
vector carrying the enhanced green fluorescent protein marker gene was
used to demonstrate that a morphologically similar subset of cells
infected in the injected knee joint are able to traffic to the
uninjected contralateral knee joint. Our results suggest that direct,
local intraarticular delivery of the vIL-10 gene may have polyarticular
therapeutic effects.
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W OLLIER Rheumatoid arthritis and Epstein-Barr virus: a case of living with the enemy? Ann Rheum Dis, July 1, 2000; 59(7): 497 - 499. [Full Text]
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