PMID: 17708739Oct 10, 2007Paper

Interleukin-6--a key mediator of systemic and local symptoms in rheumatoid arthritis

Bulletin of the NYU Hospital for Joint Diseases
Bruce N Cronstein

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine, present at elevated levels in patients with rheumatoid arthritis (RA). Il-6 signaling involves both a specific IL-6 receptor (IL-6R) and a ubiquitous signal-transducing protein, gp130 that is also utilized by other members of the IL-6 family. Il-6 signaling occurs by two mechanisms. Conventional signaling involves the binding of IL-6 to transmembrane IL-6R on cells expressing this receptor. In contrast, trans-signaling involves binding between the complex of soluble IL-6R/IL-6 and membrane-bound gp130. Trans-signaling allows IL-6 to affect cells that do not express IL-6R, including many synovial cells. The biological activities of IL-6 contribute to both systemic and local RA symptoms. Il-6 is a strong inducer of the acute-phase response, which can result in fever, secondary amyloidosis, anemia, and elevations in acute-phase proteins, such as C-reactive protein (CRP). The ability of IL-6 to induce B-cell differentiation may lead to the formation of rheumatoid factor and other autoantibodies. In joints, IL-6 promotes osteoclast activation and induces the release of matrix metalloproteinases, thus contributing to joint damage. In patients with RA, IL-6 levels correlate with markers ...Continue Reading

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