Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein.
OBJECTIVE
To investigate the role of interleukin-17 (IL-17) in inflammatory arthritis by blockade with an IL-17 receptor/human IgG1 Fc fusion protein (muIL-17R:Fc) in adjuvant-induced arthritis (AIA) in the rat.


METHODS
AIA was induced in 39 DA rats with the use of Freund's complete adjuvant. Rats received either 7.3 or 20 mg/kg of muIL-17R:Fc or phosphate buffered saline intraperitoneally every other day from the time of arthritis induction for approximately 17 days. Paw volume, arthritis severity, and weight were assessed every 3-4 days. Rats were killed between days 21 and 23 post-induction. Ankles were removed for quantitative radiology and histology and for immunohistochemistry for T cells.


RESULTS
Treatment with muIL-17R:Fc attenuated paw volume in a dose-dependent manner. Both the 7.3 and 20 mg/kg doses of muIL-17R:Fc significantly reduced radiographic scores in the treated rats compared with the controls. The 20 mg/kg dose of muIL-17R:Fc significantly reduced histology scores compared with the controls. T cell numbers were unchanged in the muIL-17R:Fc-treated rats as a function of dose.


CONCLUSIONS
In vivo blockade of IL-17 by muIL-17R:Fc treatment attenuated AIA and reduced joint damage, suggesting that IL-17 plays an important role in the inflammation and joint destruction of AIA. IL-17 may be a potential therapeutic target for inflammatory diseases in humans, such as rheumatoid arthritis.
Bush
Katherine A
KA
University of New South Wales, Sydney, New South Wales, Australia.
Farmer
Katherine M
KM
Walker
Judith S
JS
Kirkham
Bruce W
BW
D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D001175:Arthrography; D007141:Immunoglobulin Fc Fragments / Q000235:genetics*; D007074:Immunoglobulin G / Q000235:genetics*; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051381:Rats; D018123:Receptors, Interleukin / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000235:genetics*; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins