| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
This article has been cited by other articles:
|
|
 |
|
  M Hegen, J C Keith Jr, M Collins, and C L Nickerson-Nutter Utility of animal models for identification of potential therapeutics for rheumatoid arthritis Ann Rheum Dis, November 1, 2008; 67(11): 1505 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Evans, P. D. Robbins, S. C. Ghivizzani, M. C. Wasko, M. M. Tomaino, R. Kang, T. A. Muzzonigro, M. Vogt, E. M. Elder, T. L. Whiteside, et al. Gene transfer to human joints: Progress toward a gene therapy of arthritis PNAS, June 14, 2005; 102(24): 8698 - 8703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Kim, E. R. Lechman, N. Bianco, R. Menon, A. Keravala, J. Nash, Z. Mi, S. C. Watkins, A. Gambotto, and P. D. Robbins Exosomes Derived from IL-10-Treated Dendritic Cells Can Suppress Inflammation and Collagen-Induced Arthritis J. Immunol., May 15, 2005; 174(10): 6440 - 6448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lucas and G. McFadden Secreted Immunomodulatory Viral Proteins as Novel Biotherapeutics J. Immunol., October 15, 2004; 173(8): 4765 - 4774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. B. Mehta and G. E. Besner Inhibition of NF-{kappa}B Activation and Its Target Genes by Heparin-Binding Epidermal Growth Factor-Like Growth Factor J. Immunol., December 1, 2003; 171(11): 6014 - 6022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Shenker, R. Haigh, E. Roberts, P. Mapp, N. Harris, and D. Blake A review of contralateral responses to a unilateral inflammatory lesion Rheumatology, November 1, 2003; 42(11): 1279 - 1286. [Full Text] [PDF]
|
|
|
|
 |
|
 N Wilkinson, G Jackson, and J Gardner-Medwin Biologic therapies for juvenile arthritis Arch. Dis. Child., March 1, 2003; 88(3): 186 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shen, N. Taylor, L. Duncan, I. Kovesdi, J. T Bruder, J. V Forrester, and A. D Dick Ex vivo adenovirus mediated gene transfection of human conjunctival epithelium Br J Ophthalmol, July 1, 2001; 85(7): 861 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nonomura, H. Kohsaka, K. Nasu, Y. Terada, M.-a. Ikeda, and N. Miyasaka Suppression of arthritis by forced expression of cyclin-dependent kinase inhibitor p21Cip1 gene into the joints Int. Immunol., June 1, 2001; 13(6): 723 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Quattrocchi, M. J. Dallman, A. P. Dhillon, A. Quaglia, G. Bagnato, and M. Feldmann Murine IL-10 Gene Transfer Inhibits Established Collagen-Induced Arthritis and Reduces Adenovirus-Mediated Inflammatory Responses in Mouse Liver J. Immunol., May 15, 2001; 166(10): 5970 - 5978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Crawley, S. Kon, and P. Woo Hereditary predisposition to low interleukin-10 production in children with extended oligoarticular juvenile idiopathic arthritis Rheumatology, May 1, 2001; 40(5): 574 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Kim, S. Kim, C. H. Evans, S. C. Ghivizzani, T. Oligino, and P. D. Robbins Effective Treatment of Established Murine Collagen-Induced Arthritis by Systemic Administration of Dendritic Cells Genetically Modified to Express IL-4 J. Immunol., March 1, 2001; 166(5): 3499 - 3505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nasu, H. Kohsaka, Y. Nonomura, Y. Terada, H. Ito, K. Hirokawa, and N. Miyasaka Adenoviral Transfer of Cyclin-Dependent Kinase Inhibitor Genes Suppresses Collagen-Induced Arthritis in Mice J. Immunol., December 15, 2000; 165(12): 7246 - 7252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Setoguchi, Y. Misaki, Y. Araki, K. Fujio, K. Kawahata, T. Kitamura, and K. Yamamoto Antigen-Specific T Cells Transduced with IL-10 Ameliorate Experimentally Induced Arthritis Without Impairing the Systemic Immune Response to the Antigen J. Immunol., November 15, 2000; 165(10): 5980 - 5986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Russell Update on adenovirus and its vectors J. Gen. Virol., November 1, 2000; 81(11): 2573 - 2604. [Full Text]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
