Emerging role of IL-23 in rheumatoid arthritis

Abstract

Dear Editor, Emerging evidence suggests that Th17 cells play a role in rheumatoid arthritis (RA) and is dependent on IL-23 for their survival and expansion [1]. Along this line, Singh et al. [2] reported that Th17 associated cytokines, particularly IL-17, IL-1β, IL-6, IL-21, IL-23, and TGF-β, in synovial fluid of reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) patients. They found that high levels of IL-17, IL-6, and IL-1β in synovial fluid of ReA and uSpA patients. This study is interesting, which suggests that serum levels of IL-17, IL-6, and IL-1β may be considered as a biologic tool of disease activity assessment in RA patients. Meanwhile, in the study, IL-23 could not be detected in synovial fluid using an IL-23 ELISA Kit. However, this report is in contrast with previous reports showing that systemic levels of IL-23 are strongly associated with disease activity in RA [3]. Moreover, Rasmussen et al. [4] confirmed that patients with early stage RA had significantly increased plasma levels of IL23. Interestingly, the expression of IL-23 p19 mRNA and protein was enhanced in the synovial fluid, serum, and synovial tissue of RA patients correlated with the presence of bone erosions, whereas both of them were absent in health and osteoarthritis [5]. Stamp et al. [6] also showed that IL-23 p19 gene expression was higher in IL-17Apositive synovial membranes. A functional study of cultured synovial cells isolated from patients with RA showed that IL-23 blockade with IL-23 receptor results to obvious decreases in the production of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 [7]. Using animal models for arthritis, such as collagen-induced arthritis (CIA), IL-23p19 mice did not develop clinical signs of CIA and were completely resistant to the development of CIA. Moreover, treatment of neutralizing IL-23 also attenuates CIA in rats [8]. These findings hinted that IL-23 has a major role in the development of RA. In addition, authors also identified IL-23 gene polymorphisms which were associated with susceptibility to RA [9]. Although much remains to be explored about roles of IL23 in RA, a solid basis of data from in vitro and in vivo is now accumulating to support the therapeutic potential of IL-23 in RA. Therefore, further studies are required, especially in human systems, to comprehensively explore the therapeutic potential of IL-23 in RA. The development of therapeutic agents targeting IL-23 could result in important, new innovative therapies for the treatment of RA and other autoimmune diseases.