Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

INTRODUCTION: The objective of this study was to investigate the effects of tumor necrosis factor (TNF)-α inhibitors on circulating T helper-type 17 (Th17) cells and Th17-related cytokines in patients with rheumatoid arthritis (RA). METHODS: The frequencies of circulating Th17 cells and serum levels of Th17-related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 48 RA patients both before (baseline) and six months after anti-TNF-α therapy. Therapeutic response was evaluated using European League Against Rheumatism (EULAR) response criteria. RESULTS: Significantly higher baseline frequencies of circulating Th17 cells and serum levels of interleukin (IL)-6, IL-17, IL-21, IL-23 and TNF-α were observed in active RA patients than in 12 healthy controls (all P < 0.001). After anti-TNF-α therapy, 36 patients (75%) were EULAR responders (20 good responders and 16 moderate responders) and 12 (25.0%) were non-responders. The mean levels of circulating Th17 cells and IL-17 significantly decreased (1.13% vs. 0.79%; 43.1 pg/ml vs. 27.8 pg/ml; respectively, both P < 0.001) in parallel with clinical remission in responders. Levels of IL-6, IL-21, IL-23 and TNF-α were significantly decreased after anti-TNF-α therapy in responders. In contrast, the mean levels of circulating Th17 cells and IL-17 significantly increased after anti-TNF-α therapy (2.94% vs. 4.23%; 92.1 pg/ml vs. 148.6 pg/ml; respectively, both P < 0.05) in non-responders. Logistic regression analysis identified a high baseline level of IL-17 as a significant predictor of poor therapeutic response. CONCLUSIONS: The beneficial effect of anti-TNF-α therapy might involve a decrease in Th17-related cytokines in responders, whereas rising levels of circulating Th17-cells and IL-17 were observed in patients with an inadequate response to anti-TNF-α therapy.