IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis

T cell IL-17 displays proinflammatory properties and is expressed in the sy novium of patients with rheumatoid arthritis. Its contribution to the arthr itic process has not been identified. Here, we show that blocking of endoge nous IL-17 in the autoimmune collagen-induced arthritis model results in su ppression of arthritis. Also, joint damage was significantly reduced. In co ntrast, overexpression of IL-17 enhanced collagen arthritis. Moreover, aden oviral IL-17 injected in the knee joint of type II collagen-immunized mice accelerated the onset and aggravated the synovial inflammation at the site. Radiographic and histologic analysis showed markedly increased joint destr uction. Elevated levels of IL-1 beta protein were found in synovial tissue. Intriguingly, blocking of IL-1 alpha beta with neutralizing Abs had no eff ect on the IL-17-induced inflammation and joint damage in the knee joint, i mplying an IL-1 independent pathway. This direct potency of IL-17 was under scored in the unabated IL-17-induced exaggeration of bacterial cell wall-in duced arthritis in IL-1 beta (-/-) mice. In conclusion, this data shows tha t IL-17 contributes to joint destruction and identifies an IL-1-independent role of IL-17. These findings suggest IL-17 to be a novel target for the t reatment of destructive arthritis and may have implications for tissue dest ruction in other autoimmune diseases.