Systemic effects of IL-17 in inflammatory arthritis

Inflammatory arthritis occurs in many diseases and is characterized by joint inflammation and damage. However, the inflammatory state in arthritis is commonly associated with systemic manifestations, which are generally linked to a poor prognosis. The pro-inflammatory cytokine IL-17 functions within a complex network of cytokines and contributes to the pathogenesis of various inflammatory diseases. Three IL-17 inhibitors have already been approved for the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. After a brief description of IL-17 and its local effects on joints, this Review focuses on the systemic effects of IL-17 in inflammatory arthritis. Increased circulating concentrations of bioactive IL-17 mediate changes in blood vessels, liver and cardiac and skeletal muscles. The effects of IL-17 on vascular and cardiac cells might contribute to the increased risk of cardiovascular events that occurs in all patients with inflammatory disorders. In the liver, IL-17 contributes to the high circulating concentrations of acute-phase proteins, such as C-reactive protein, and the appearance of liver lesions. In skeletal muscle, IL-17 contributes to muscle contractibility defects and weakness. Thus, targeting IL-17 might have beneficial effects at both local and systemic levels, and could also be proposed for the treatment of a wider range of inflammatory diseases.