Relative expression and correlation of tumor necrosis factor-α, interferon-γ, and interleukin-17 in the rheumatoid synovium

Although tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), 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-gamma, IL-17, and TNF-alpha 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-gamma, IL-17, and TNF-alpha was performed. Correlation of expression levels between them was also analyzed. Expression levels of TNF-alpha, IFN-gamma, 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-gamma plus TNF-alpha-dominant type, an IL-17-dominant type, and the other type. TNF-alpha expression levels were correlated with IFN-gamma. In addition, there was a negative correlation between TNF-alpha and IL-17, and IFN-gamma and IL-17. Median relative expression levels of TNF-alpha have no significant difference between the TNFi and the csDMARDs groups. In the rheumatoid synovial tissues, expression levels of TNF-alpha were modulated in parallel with IFN-gamma, and TNF-alpha and IL-17, or IFN-gamma 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.