Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer are equally effective in ameliorating disease pathology in a rabbit knee model of antigen-induced arthritis

Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA.
Arthritis research & therapy (Impact Factor: 3.75). 02/2006; 8(4):R91. DOI: 10.1186/ar1960
Source: PubMed


IL-10 is a Th2 cytokine important for inhibiting cell-mediated immunity while promoting humoral responses. Human IL-10 (hIL-10) has anti-inflammatory, immunosuppressive as well as immunostimulatory characteristics, whereas viral IL-10 (vIL-10), a homologue of hIL-10 encoded by Epstein Barr virus (EBV), lacks several immunostimulatory functions. The immunostimulatory characteristic of hIL-10 has been attributed to a single amino acid, isoleucine at position 87, which in vIL-10 is alanine. A mutant hIL-10 in which isoleucine has been substituted (mut.hIL-10) is biologically active with only immunosuppressive, but not immunostimulatory, functions, making it a potentially superior therapeutic for inflammatory diseases. To compare the efficacy of mut.hIL-10 with hIL-10 and vIL-10 in blocking the progression of rheumatoid arthritis, we used replication defective adenoviral vectors to deliver intra-articularly the gene encoding hIL-10, vIL-10 or mut.hIL-10 to antigen-induced arthritic (AIA) knee joints in rabbits. Intra-articular expression of hIL-10, vIL-10, and mut.hIL-10 resulted in significant improvement of the pathology in the treated joints to similar levels. These observed changes included a significant reduction in intra-articular leukocytosis and the degree of synovitis, as well as normalization of cartilage matrix metabolism. Our results suggest that hIL-10, vIL-10, and mut.hIL-10 are all equally therapeutic in the rabbit AIA model for treating disease pathology.


Available from: Eric R Lechman
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    • "The present study is the first work in which WJ-hMSCs have been transduced with EBV-derived vIL-10, which has been extensively studied and is well known to have immunosuppressive properties. This cytokine-like molecule has been tested in several animal models and has proved effective at inhibiting collagen-induced arthritis, suppressing autoimmune diabetes and improving survival to sepsis [35,37,68697071 . Furthermore, in several transplantation models vIL-10 consistently increased graft survival compared with hIL-10 [3,30,69,72,73]. "
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    • "AIA in rabbits provides one of the best models of RA available. The rabbit knee joint is anatomically similar to the human knee joint, the area of the body with the highest incidence of RA (Kerevala 2006). The joint histopathology of AIA closely resembles RA, and its responsiveness to anti-rheumatic and antiinflammatory drugs is similar to that of the clinical disease (Glynn 1968, Zvaifler 1973, Foong 1996). "
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    Full-text · Article · Jan 2008 · Journal of Drug Targeting
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