Monocyte Derived Interleukin (IL)-23 Is an Important Determinant of Synovial IL-17A Expression in Rheumatoid Arthritis

Objective. To demonstrate gene expression of interleukin (IL)-17A, IL-23, and IL-12 and to determine the proximity of IL-17A and 11-23 producing Cells in rheumatoid synovial tissue. Methods. Total RNA was isolated from 25 synovial membranes obtained from 20 patients with rheumatoid arthritis (RA). Quantitative real-time polymerase chain reaction was used to measure IL-17A, IL-12p35, IL-23p19 p40, and GAPDH expression. Immunohistochemistry was utilized to determine cell type and proximity of IL-17A, IL-12, and IL-23 in rheumatoid synovium. Results. IL-17A was present in 13/25 synovia. IL-12p35 was present in all samples while IL-23p19 was present in 23/25. p40 was present in 23/25 samples. Of the 2 p40- samples both were IL-23p19 and IL-12p35 positive. Mean expression of IL-23p19 was significantly higher in the IL-17A+ versus IL-17A- synovia (0.10 +/- 0.02 no vs 0.05 +/- 0.01 no; p < 0.05). There was no difference in IL-12p35 expression between IL-17A+ and IL-17A- synovia (0.5 +/- 0.21 ng vs 0.38 +/- 0.24 no; p = 0.2). All IL-17A+ cells were in the vicinity of IL-23+ cells. IL-12+ cells were both close to and removed from IL-17A+ cells. Only a proportion of CD3+T cells appeared to produce IL-17A. Conclusion. IL-17A gene expression occurs in only a subset of rheumatoid synovial membranes. IL-23 gene expression is higher in IL-17A+ versus IL-17A- membranes. In keeping with this, IL-17A+ and IL-23+ cells colocalize in synovial membranes. IL-17 is not an absolute requirement in RA but may be important in amplifying the inflammatory response. Anti-IL23 therapies may have a role in those patients with IL-17A expression. (First Release Oct 1 2009; J Rheurnatol 2009;36:2403-8; doi: 10.3899/jrheum.081304)