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Prolonged increase of serum IL-6 levels can cause numerous systemic manifestations of RA, including abnormal lipid metabolism, cardiovascular disease (CVD), anemia, osteoporosis, fatigue, mood disorders, pain, and morning stiffness.1-3
Serum IL-6 levels are highest in the early morning hours when patients with RA most often experience articular pain and stiffness, as well as functional disability.5
Adapted from Crofford 1997.
Nearly 4X higher early morning levels of IL-6 in patients with RA5
Elevated IL-6 plays a central role in osteoclast activation, tissue damage, joint destruction, and bone loss.1,2
References: 1. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):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. Ota M, Yanagisawa M, Tachibana H, et al. A significant induction of neutrophilic chemoattractants but not RANKL in synoviocytes stimulated with interleukin 17. J Bone Miner Metab. 2015;33(1):40-47. 5. 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. 6. 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.