IL-23/IL-17 axis in the pathogenesis and therapy of axial spondyloarthritis associated with inflammatory

In spite of obvious role of IL-17 in the pathogenesis of IBD and axial spondyloarthritis, recently, in combination of these pathologies, usage of targeted drugs aimed at IL-17 and IL-23 requires special caution. Thus, using an IL-17A inhibitor in patients with axial spondyloarthritis associated with IBD, it is possible to prevent the progression of spondyloarthritis, but cause exacerbation of IBD. In turn, using an IL-23 inhibitor in such patients, can expect remission of IBD, but progression of spondyloarthritis. The purpose of our literature review is to identify and explain the cause of such observations. In IBD, IL-23 promotes the formation of "pathogenic" Th17, and inhibition of this cytokine appears to be somewhat effective, since IL-17A production by "nonpathogenic" Th17 in the intestinal mucosa remains unchanged. At the same time, in axial spondyloarthritis, IL-23 plays an important role only in the initiation of the pathological process, rather than in maintaining joint damage in an already established disease, which may explain the ineffectiveness of targeted drugs aimed at this cytokine. Exacerbation of IBD with IL-17A inhibition may be explained by disruption of IL-17-induced intercellular epithelial contacts. However, IL-17A inhibitors are quite effective in the treatment of axial spondyloarthritis, since they prevent IL-17-induced inflammation and bone destruction. We also suggest that IL-17A in axial spondyloarthritis is secreted predominantly by myeloid cells rather than Th17. Thus, in the pathogenesis of axial spondyloarthritis associated with inflammatory bowel diseases, the IL-23/ IL-17 axis plays a central role. However, modulation of the IL-17 signaling cascade in this situation remains ambiguous and requires further study.

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