This lecture will explore the central importance of the powerful, pro-inflammatory cytokine interleukin(IL)-23 in spondyloarthropathy. Although the pathogenesis of these conditions has been highly enigmatic for decades, numerous lines of investigation have recently independently converged upon IL-23, demonstrating it to be fundamental to the biology of spondyloarthropathy. Thus the bowel inflammation which is associated with spondyloarthropathy results in production of IL-23 and HLA-B27, which itself is very strongly associated with these conditions, has also been shown to misfold and trigger production of IL-23. Moreover genetic studies have demonstrated that polymorphisms in the receptor for IL-23 are associated with the risk of developing spondyloarthropathy. We have recently explored the direct mechanism of IL-23 action in this context to show that IL-23 acts directly on the hallmark anatomical sites affected in spondyloarthropathy, such as the entheseal attachments of tendons and ligaments to bone and the aortic root. These findings not only clarify the pathogenesis of these conditions but open exciting new therapeutic approaches for their treatment.
Disclosure of Interest J. Sherlock Employee of: Work presented in this seminar was conducted wtihin Merck