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Open Access Highly Accessed Research article

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

Der-Yuan Chen1234, Yi-Ming Chen12, Hsin-Hua Chen12, Chia-Wei Hsieh123, Chi-Chen Lin4 and Joung-Liang Lan1234*

Author Affiliations

1 Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, No. 160, Section 3, Taichung-Kang Road, Taichung, 407, Taiwan

2 Faculty of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Street, Taipei 112, Taiwan

3 School of Medicine, Chung-Shan Medical University, No.110, Sec.1, Jianguo N.Rd., Taichung, 402, Taiwan

4 Institute of Biomedical Science, National Chung-Hsing University, No.250, Kuo-Kuang Rd., Taichung, 402, Taiwan

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Arthritis Research & Therapy 2011, 13:R126  doi:10.1186/ar3431

Published: 30 July 2011

Abstract

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.