LAUSR

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<0.0001, p=0.0003). On the other hand, TCZ significantly up-regulated the expression of IL-17 as compared to medium control (p=0.05) (Figure 1A). The frequency of activated CD4+CD25+ T cells was down-regulated by ADA as compared to medium and TCZ, respectively (p=0.03, p=0.005). whereas activated CD4+CD25+ T cells were up-regulated by TCZ (although not significantly) as compared to medium control (n=60) (Figure 1B).Abstract THU0030 – Figure 1 ADA and TCZ differentially modulates IL-17 mRNA expression and activated CD4+CD25+ T cells in PBMC derived from PsA patients. PBMC were co-cultured in the presence of ADA,TCZ or medium alone as a control. (A) After 72 h incubation RNA was extracted and real-time PCR for quantification of IL-17 was performed.(n=20). (B) After 5 days incubation change in%CD4+CD25+ T cells was determined by flow cytometry (n=60), ns=not significant. 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