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Autoimmun Rev. 2009 Jun;8(7):538-42. doi: 10.1016/j.autrev.2009.01.012. Epub 2009 Feb 2.

Interleukin-6 as a key player in systemic inflammation and joint destruction.

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Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.


Interleukin-6 (IL-6) is a cytokine that can facilitate autoimmune phenomena, amplify acute inflammation and promote the evolution into a chronic inflammatory state. In addition, it is a major promoter of bone resorption in pathological conditions. In particular, IL-6 has a pivotal role in synovitis, bone erosions and in the systemic features of inflammation. This cytokine specifically binds to IL-6 receptor (IL-6R), forming the IL-6/IL-6R complex that binds to gp130, a membrane-bound protein, which is involved in non-ligand-binding signal transduction. Targeting IL-6R in both animal models of arthritis and in rheumatoid arthritis patients with a humanized anti IL-6R monoclonal antibody (tocilizumab) effectively controls local and systemic inflammatory manifestations and blocks cartilage and bone destruction. Given the pleiotropic function of IL-6 it can be anticipated that other inflammatory diseases and bone metabolic conditions might benefit from selective IL-6 signaling inhibition.

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