WHAT ROLE ELEVATED IL-6 CAN PLAY IN RA

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WHAT ROLE ELEVATED IL-6 CAN PLAY IN RA

Elevated IL-6 and RA

The inflammatory milieu of rheumatoid arthritis (RA) is driven by a complex network of pro-inflammatory cytokines, including interleukin-6 (IL-6), and other immune processes.1,2

IL-6 is one of the most abundant cytokines in the serum and synovial fluid of the inflamed joints in patients with RA. When elevated, IL-6 has been associated with disease activity, articular destruction, and systemic manifestations.2

Because of its dual signaling mechanism, dysregulated IL-6 affects the function of many tissues and processes, promoting1,2:

  • Chronic systemic inflammation
  • Production of autoantibodies that form immune complexes and stimulate pro-inflammatory cytokine production
  • Joint destruction

Persistently high serum levels of IL-6 correlate with morning stiffness, disease severity, and joint damage progression.2,3

Adapted from Dayer 2010.

Inflammatory pathways activated by IL-6. In the joints, IL-6 induces pannus formation and osteoclast activation and mediates chronic synovitis2

Adapted from Dayer 2010.

Inflammatory pathways activated by IL-6. In the joints, IL-6 induces pannus formation and osteoclast activation and mediates chronic synovitis2

IL-6 and articular manifestations of RA

Elevated IL-6 plays a central role in osteoclast activation, tissue damage, joint destruction, and bone loss.1,2

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IL-6 and systemic manifestations of RA

Overproduction of IL-6 can contribute to systemic manifestations, including hypolipidemia, acute-phase protein production, cardiovascular disease, anemia of chronic inflammation, osteoporosis and osteopenia, fatigue, autoimmunity, and morning stiffness.2,4,5

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References: 1. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl5):v3-v11. 2. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24. 3. Gibbs JE, Ray DW. The role of the circadian clock in rheumatoid arthritis. Arthritis Res Ther. 2013;15(1):1-9. 4. Crofford LJ, Kalogeras KT, Mastorakos G, et al. Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab. 1997;82(4):1279-1283. 5. Perry MG, Kirwan JR, Jessop DS, Hunt LP. Overnight variations in cortisol, interleukin 6, tumour necrosis factor alpha and other cytokines in people with rheumatoid arthritis. Ann Rheum Dis. 2009;68(1):63-68.