Impact on

IL-6 manifestations can diminish patient quality of life1-3

IL-6 orchestrates many of the inflammatory activities within the synovium, resulting in debilitating articular manifestations such as morning stiffness and joint destruction.4,5 More importantly, elevated IL-6 also results in many systemic manifestations that may affect patient quality of life.2-5 IL-6 promotes expression of C-reactive protein and hepcidin, acute-phase proteins that are a key part of the acute- phase response seen in many patients with RA.4

RA is more than a disease of the joints

Systemic manifestations of IL-6 and RA include: osteoporosis, osteopenia, anemia, acute-phase response (e.g. elevated CRP), cardiovascular risk, metabolic dysregulation (e.g. Insulin resistance, dyslipidemia), fatigue, mental health effects and pain. Articular manifestations of IL-6 and RA include: morning stiffness and joint destruction.

Uncovering the systemic effects of elevated IL-62,4,6-9

  • Pain


    IL-6 helps mediate pain through direct action on the nociceptive system2

  • Mental Health

    Mental Health

    IL-6 can affect mental health and cause fatigue via its action on the hypothalamic-pituitary-adrenal axis2

  • Sleep


    IL-6 has been linked to sleep disruption2,7

  • Heart and Blood

    Heart and Blood

    IL-6 contributes to numerous changes in cardiovascular and hematologic parameters commonly seen in patients with RA6,8

  • Matabolism


    IL-6 can affect lipid metabolism, thereby contributing to metabolic manifestations of RA such as dyslipidemia and insulin resistance4,6,8,9

Beyond the joints: systemic manifestations of IL-6 elevation in rheumatoid arthritis
by Dr Grace Wright

IL-6 effects on bone resorption

In addition to articular and systemic effects, elevated IL-6 can affect bone resorption.1,4 Elevated IL-6 signaling favors osteoclast over osteoblast function, promoting bone resorption that may manifest as both articular and systemic bone loss.4,5

Schematic view of a normal joint (A) and a joint affected by RA (B)

Schematic view of a normal joint compared to a joint affected by RA
Adapted from Choy, 2012.1

References: 1. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):v3-v11. doi:10.1093/rheumatology/kes113. 2. Choy EHS, Calabrese LH. Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis. Rheumatology (Oxford). 2018;57(11):1885-1895. 3. Malm K, Bergman S, Andersson ML, Bremander A, Larsson I. Quality of life in patients with established rheumatoid arthritis: a phenomenographic study. SAGE Open Med. 2017;5:2050312117713647. 4. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24. 5. Cutolo M, Straub RH, Buttgereit F. Circadian rhythms of nocturnal hormones in rheumatoid arthritis: translation from bench to bedside. Ann Rheum Dis. 2008;67(7):905-908. 6. Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation. 2003;108(24):2957-2963. 7. Vgontzas AN, Bixler EO, Lin H-M, Prolo P, Trakada G, Chrousos GP. IL-6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12(3):131-140. 8. Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum. 2005;35(1):8-17. 9. Kerekes G, Nurmohamed MT, González-Gay MA, et al. Rheumatoid arthritis and metabolic syndrome. Nat Rev Rheumatol. 2014;10(11):691-696.