Abstract
Although tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-17 (IL-17) play important roles in RA, their relative expression and possible correlation in synovial tissues are not well understood. In this study, mRNA expression levels of IFN-γ, IL-17, and TNF-α were investigated in individual patients with RA and the correlations between pairs of these three pro-inflammatory cytokines were analyzed. Synovial tissues were obtained during arthroplasties from 24 joints of 24 RA patients. After harvesting synovial tissues, total RNA was isolated then quantitative real-time polymerase chain reaction (qRT-PCR) for IFN-γ, IL-17, and TNF-α was performed. Correlation of expression levels between them was also analyzed. Expression levels of TNF-α, IFN-γ, and IL-17 in patients receiving TNF inhibitors (TNFi) and those treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone were also compared between groups. Based on relative expression levels of the three pro-inflammatory cytokines, patients were classified into three major types; an IFN-γ plus TNF-α-dominant type, an IL-17-dominant type, and the other type. TNF-α expression levels were correlated with IFN-γ. In addition, there was a negative correlation between TNF-α and IL-17, and IFN-γ and IL-17. Median relative expression levels of TNF-α have no significant difference between the TNFi and the csDMARDs groups. In the rheumatoid synovial tissues, expression levels of TNF-α were modulated in parallel with IFN-γ, and TNF-α and IL-17, or IFN-γ and IL-17 did not co-express at high levels. This characteristic expression pattern of the three pro-inflammatory cytokines may be clinically useful information in the current cytokine-targeted treatment with biological DMARDs for RA.
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Acknowledgments
This work was supported in part by Grant-in-Aid (23592233 to A. N., 23592234 to M. So.) from the Ministry of Education, Science, Technology, Sports and Culture of Japan, the Futaba Electronics Memorial Foundation (A. N.), the Takeda Science Foundation (A. N.), the Research Promotion Grant from Toho University Graduate School of Medicine (No. 12-03 to A. N.), and the Hamaguchi Foundation for the Advancement of Biochemistry (A. N.)
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Written informed consent was obtained from all the patients prior to surgery. The study protocol was approved by the Ethical Committee for Clinical Research at Toho University (Approved No. 2013-009).
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Nakajima, A., Aoki, Y., Sonobe, M. et al. Relative expression and correlation of tumor necrosis factor-α, interferon-γ, and interleukin-17 in the rheumatoid synovium. Clin Rheumatol 35, 1691–1697 (2016). https://doi.org/10.1007/s10067-016-3249-2
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DOI: https://doi.org/10.1007/s10067-016-3249-2