THU0030 THE DIFFERENTIAL EFFECT OF TNF-α AND IL-6R BLOCKERS ON THE EXPRESSION OF IL-17 AND ACTIVATED CD4+CD25+ T CELLS IN PATIENTS WITH PSORIATIC ARTHRITIS

ANNALS OF THE RHEUMATIC DISEASES(2019)

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摘要
Background TNF-α blockers are effective drugs for the treatment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). On the other hand, while interleukin-6 receptor (IL-6R) blockers have emerged as effective drugs in the treatment of RA, their effect in PsA has been disappointing. We hypothesized that the differential effect of TNF-α and IL-6R blockers in PsA may be mediated by the effect of these drugs on IL-17 expression, a cytokine profoundly involved in PsA and by their influence on activated CD4+CD25+ T cells. Objectives To evaluate the differential effect of adalimumab (ADA) (representing TNF-α blockers) and tocilizumab (TCZ) (IL-6R blocker) on the expression level of IL-17 and on the frequency of activated CD4+CD25+ T cells. Methods Levels of IL-17 mRNA expression were measured following in vitro co-culture of peripheral blood mononuclear cells (PBMC) derived from PsA patients with, ADA, TCZ at 10ug/ml or with medium alone as control for 3 days. Next, RNA was extracted and real-time PCR for IL-17 mRNA expression was performed. In addition, after 5 days incubation with the biologic agents the frequency of activated CD4+CD25+ T cells were analyzed by flow cytometry. Results The differential effect of ADA and TCZ on IL-17 mRNA expression and modulation of activated CD4+CD25+ T cells in culture of PBMC derived from PsA patients is shown in Figure 1. We found that IL-17 mRNA expression in PsA patients derived PBMC (n=20) was down-regulated by ADA. This down grading was significant in comparison with TCZ and medium control respectively (p Conclusion Our data highlight the differential effect of ADA and TCZ on IL-17 expression level and on frequency of activated CD4+CD25+ T cells in culture of peripheral immune cells derived from PsA patients. This data suggest a new mechanism of action of ADA and provide a possible explanation of the inefficacy of TCZ in PsA. Disclosure of Interests None declared
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