The biology of IL-23 and IL-17 and their therapeutic targeting in rheumatic diseases.
Sherlock JP., Taylor PC., Buckley CD.
Interleukin (IL)-23 and the related cytokine IL-17 play vital roles in immune-mediated inflammatory pathology. In the years since its discovery, IL-23 has been implicated as a central pathogenic factor in multiple rheumatic conditions and has been shown to act via a wide range of immune cells including type 17 T-helper (Th17) cells and innate-like immune cells. We review here the pivotal role of these cytokines and IL-23-responsive cells in both the bona fide autoimmune rheumatic diseases rheumatoid arthritis and systemic lupus erythematosus, as well as the spondyloarthropathies which more closely resemble the auto-inflammatory conditions.IL-23 and related cytokines have been found to be up-regulated in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy, and preclinical models suggest that they play important pathological roles in these conditions.It is anticipated that agents which target the IL-23 pathway will have profound roles in modifying the natural history of these diseases and in preventing the structural damage which occurs secondary to such chronic inflammation. This is especially relevant in the case of spondyloarthropathy in which case prevention of the novel bone formation is a particular challenge. It is also potentially pertinent for patients with rheumatoid arthritis, particularly those who do not respond to other biological therapies.