title: Interleukin-13 gene therapy reduces inflammation, vascularization, and bony destruction in rat adjuvant-induced arthritis.
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-alpha (TNF-alpha) 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.
authors.affiliation: Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Woods
authors.forename: M Asif
authors.initials: MA
authors.lastname: Amin
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Katschke
authors.forename: Michael V
authors.initials: MV
authors.lastname: Volin
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ruth
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Connors
authors.forename: Drew C
authors.initials: DC
authors.lastname: Woodruff
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurata
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Arai
authors.forename: G Kenneth
authors.initials: GK
authors.lastname: Haines
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000842:Ankle / Q000473:pathology / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005347:Fibroblasts; D015316:Genetic Therapy; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D009161:Mycobacterium; D051381:Rats
chemical_list: D018793:Interleukin-13