Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin‐17 receptor IgG1 Fc fusion protein
KA Bush, KM Farmer, JS Walker… - Arthritis & …, 2002 - Wiley Online Library
KA Bush, KM Farmer, JS Walker, BW Kirkham
Arthritis & Rheumatism, 2002•Wiley Online LibraryObjective 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∼ 17 days. Paw volume, arthritis severity, and weight were assessed every 3–4 …
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∼ 17 days. Paw volume, arthritis severity, and weight were assessed every 3–4 …
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 ∼17 days. Paw volume, arthritis severity, and weight were assessed every 3–4 days. Rats were killed between days 21 and 23 postinduction. 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.
Conclusion
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.
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