Interleukin-13 gene therapy reduces inflammation, vascularization, and bony destruction in rat adjuvant-induced arthritis

James M. Woods, M. Asif Amin, Kenneth J. Katschke, Michael V. Volin, Jeffrey H. Ruth, Matthew A. Connors, Drew C. Woodruff, Hirokazu Kurata, Ken Ichi Arai, G. Kenneth Haines, Pawan Kumar, Alisa E. Koch

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial pannus formation, leukocyte infiltration, and angiogenesis. Adenoviral production of interleukin-13 (IL-13) reduces levels of proinflammatory mediators in an explant model of RA synovial tissue in vitro. To assess this approach in an animal model of arthritis, we compared intra-articular injections of an adenovirus producing rat IL-13 (AxCArIL-13), a control virus, and rat ankles receiving phosphate-buffered saline (PBS) in rat adjuvant-induced arthritis (AIA). We demonstrate that IL-13 levels are normally low in ankles throughout the course of rat AIA. We show that administration of AxCArIL-13 before arthritis onset significantly reduces ankle circumference, paw volume, bony destruction, the number of polymorphonuclear cells (PMNs), the quantity of blood vessels, and levels of monocyte chemoattractant protein (MCP)-1 in ankles. When administered as a treatment to inflamed ankles, AxCArIL-13 decreases articular index scores, paw volumes, bony destruction, vascularization, tumor necrosis factor-α (TNF-α) levels, and the quantity of monocytes, lymphocytes, and PMNs. Thus, increasing IL-13 levels significantly ameliorates the course of rat AIA, suggesting that similar strategies for the treatment of human RA are worthy of further study.

Original languageEnglish
Pages (from-to)381-393
Number of pages13
JournalHuman Gene Therapy
Volume13
Issue number3
DOIs
StatePublished - 10 Feb 2002
Externally publishedYes

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