Interleukin-13 gene therapy reduces inflammation, vascularization, and bony destruction in rat adjuvant-induced arthritis.
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.
Woods
James M
JM
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
Amin
M Asif
MA
Katschke
Kenneth J
KJ
Volin
Michael V
MV
Ruth
Jeffrey H
JH
Connors
Matthew A
MA
Woodruff
Drew C
DC
Kurata
Hirokazu
H
Arai
Ken-Ichi
K
Haines
G Kenneth
GK
Kumar
Pawan
P
Koch
Alisa E
AE
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
D018793:Interleukin-13