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 similar to17 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 MA. IL-17 may be a potential therapeutic target for inflammatory diseases in humans, such as rheumatoid arthritis.