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.
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.
Keravala
Annahita
A
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA.
Lechman
Eric R
ER
Nash
Joan
J
Mi
Zhibao
Z
Robbins
Paul D
PD
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007270:Injections, Intra-Articular; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007719:Knee Joint / Q000473:pathology*; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D011817:Rabbits
D016753:Interleukin-10; D010047:Ovalbumin