Up‐regulation of cytokines and chemokines predates the onset of rheumatoid arthritis

作者：Heidi Kokkonen, Ingegerd Söderström, Joacim Rocklöv, Göran Hallmans, Kristina Lejon, Solbritt Rantapää‐Dahlqvist · 发表于：Arthritis & Rheumatism · 年份：2010 · DOI：10.1002/art.27186 · 被引用次数：459 · 研究领域：Rheumatoid Arthritis Research and Therapies、Chemokine receptors and signaling、Systemic Lupus Erythematosus Research

OBJECTIVE: To identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA). METHODS: A nested case-control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (pre-patients) and 256 matched control subjects (1:3 ratio). In 69 of the pre-patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system. RESULTS: The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i.e., those representing signs of general immune activation (interleukin-1beta [IL-1beta], IL-2, IL-6, IL-1 receptor antagonist, and tumor necrosis factor), activation of Th1 cells (interferon-gamma, IL-12), Th2 cells (IL-4, eotaxin), Treg cells (IL-10), bone marrow-derived factors (IL-7, granulocyte-macrophage colony-stimulating factor, and granulocyte colony-stimulating factor), as well as chemokines (monocyte chemotactic protein 1 and macrophage inflammatory protein 1alpha). The levels were particularly increased in anti-cyclic citrullinated peptide antibody- and rheumatoid factor-positive individuals, and the concentration of most of these increased further after disease onset. The concentration of IL-17 in individuals before dis...