title: Relative expression and correlation of tumor necrosis factor-α, interferon-γ, and interleukin-17 in the rheumatoid synovium.
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.
authors.affiliation: Department of Orthopaedics, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan. a-nakaji@sf7.so-net.ne.jp.|Department of Rheumatology, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan. a-nakaji@sf7.so-net.ne.jp.
authors.forename: Arata
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of General Medical Sciences, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8677, Japan.|Department of Orthopaedic Surgery, Eastern Chiba Medical Center, 3-6-2 Okayamadai, Togane-shi, Chiba, 283-8686, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Orthopaedics, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Sonobe
authors.affiliation: Department of Orthopaedics, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Watanabe
authors.affiliation: Department of Orthopaedics, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Orthopaedics, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Orthopaedics, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D007564:Japan; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018501:Antirheumatic Agents; C573415:IFNG protein, human; D020381:Interleukin-17; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000068800:Etanercept
keywords: Interferon-γ (IFN-γ); Interleukin-17 (IL-17); Rheumatoid arthritis; Synovium; Tumor necrosis factor-α (TNF-α)