What role elevated IL-6 may have in RA

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Elevated IL-6 and rheumatoid arthritis (RA)

Interleukin-6 (IL-6) is one of the most abundant cytokines in the serum and synovial fluid of the inflamed joints of patients with RA. It has been associated with disease activity, articular destruction, and systemic manifestations.1

While normal levels of IL-6 are vital for homeostasis, in the inflammatory process, persistent, elevated IL-6 levels may play a role in disrupting homeostasis by affecting the function of a broad range of cells, and activating inflammatory pathways.1-10

Elevated IL-6 signaling plays a key role in chronic inflammation by stimulating and facilitating interactions between both the innate and adaptive arms of the immune system.1,10,11

Adapted from Dayer 2010.

Inflammatory pathways activated by IL-6. In the joints, IL-6 induces pannus
formation and osteoclast activation and mediates chronic synovitis1

Elevated levels of IL-6 and the soluble IL-6 receptor (sIL-6R) are associated with disease activity in RA12,13

References: 1. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24. 2. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):v3-v11. 3. Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatology. 5th ed. Philadelphia, PA: MOSBY Elsevier Ltd; 2011. 4. Janeway CJ, Travers P, Walport M, Shlomchik M. Immunobiology: The Immune System in Health and Disease. 5th ed. New York: Garland Science; 2001. 5. Ito A, Itoh Y, Sasaguri Y, Morimatsu M, Mori Y. Effects of interleukin-6 on the metabolism of connective tissue components in rheumatoid synovial fibroblasts. Arthritis Rheum. 1992;35(10):1197-1201. 6. Jansen JH, Kluin-Nelemans JC, Van Damme J, Wientjens GJ, Willemze R, Fibbe WE. Interleukin 6 is a permissive factor for monocytic colony formation by human hematopoietic progenitor cells. J Exp Med. 1992;175(4):1151-1154. 7. Okada A, Yamasaki S, Koga T, et al. Adipogenesis of the mesenchymal stromal cells and bone oedema in rheumatoid arthritis. Clin Exp Rheumatol. 2012;30(3):332-337. 8. Schmitt RM, Bruyns E, Snodgrass HR. Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Genes Dev. 1991;5(5):728-740. 9. Choy EH, Kavanaugh AF, Jones SA. The problem of choice: current biologic agents and future prospects in RA. Nat Rev Rheumatol. 2013;9(3):154-163. 10. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429-442. 11. Saxena A, Cronstein BN. Acute phase reactants and the concept of inflammation. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR, eds. Kelley’s Textbook of Rheumatology. Vol 1. 9th ed. Philadelphia, PA: Elsevier/Saunders. 2013:818-829. 12. Robak T, Gladalska A, Stepién H, Robak E. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. Med Inflamm. 1998;7(5):347-353. 13. Mallya RK, Mace BE. The assessment of disease activity in rheumatoid arthritis using a multivariate analysis. Rheum Rehab. 1981;20(1):14-17.