Regulatory immune responses induced by IL-1 receptor antagonist in rheumatoid arthritis

• Published in: Molecular immunology Vol. 49; no. 1-2; pp. 290 - 296
• Main Authors: Niu, Xiaoyin, He, Dongyi, Deng, Shaohua, Li, Weiyi, Xi, Yebin, Xie, Changyi, Jiang, Ting, Zhang, Jingwu Z., Dong, Chen, Chen, Guangjie
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2011
• Subjects: Anakinra; Antirheumatic Agents - administration & dosage; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Cell Separation; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; IL-1 receptor Antagonist; Immune regulation; Interferon-gamma - blood; Interleukin 1 Receptor Antagonist Protein - administration & dosage; Interleukin-17 - blood; Interleukin-1beta - blood; Interleukins - blood; Male; Methotrexate - administration & dosage; Middle Aged; Real-Time Polymerase Chain Reaction; Rheumatoid arthritis; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th17 Cells - drug effects; Th17 Cells - immunology; Immune regulation; Rheumatoid arthritis; Anakinra; IL-1 receptor Antagonist
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2011.08.020

► We observed the immunological changes after Anakinra treatment in RA patients. ► Serum levels of IL-17, IFN-γ, IL-21 and IL-1β significantly decreased. ► The percentages of Th17, Th1 were lower and the percentage of Treg was higher. ► Significant reduction in swollen, tender joint counts and other clinical variables. Anakinra, a human recombinant IL-1 receptor antagonist, is approved for the treatment of RA. In this study, 12 patients received the placebo plus MTX treatment, 38 patients received Anakinra combined with MTX treatment. Compared with the placebo plus MTX group, serum levels of IL-17, IFN-γ, IL-21 and IL-1β significantly decreased, the percentages of Th17 cells and Th1 cells were lower and the percentage of Treg cells was higher after receiving Anakinra combined with MTX treatment. The observed regulatory immune responses collectively correlated with clinical improvement in treated patients. A substantial response, ACR 20 at 24w were consistent with those at 12w, 16w and 20w, and was accompanied by a marked improvement in RA related laboratory parameters. The study reveals that the combination of Anakinra and MTX is safe and well tolerated, which induces regulatory immune responses and significantly provides greater clinical benefit than the placebo plus MTX group.