What role elevated IL-6 may have in RA

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Persistently elevated IL-6 levels may play a role in systemic manifestations of rheumatoid arthritis (RA)1-3

Metabolic Manifestations
  • Lipid metabolism through interactions with adipose tissue4,5
  • Low-density lipoprotein (LDL) cholesterol metabolism6
Hepatic Manifestations
  • Systemic inflammation, through its actions on the liver, which increases C-reactive protein (CRP) and serum amyloid A (SAA)1
Cardiovascular Manifestations
  • Inducer of CRP7
  • Vascular endothelial dysfunction7,8
Hematologic Manifestations
  • Hypoferremia through induction of hepcidin—a potential cause of anemia1
  • Anemia of chronic disease1
  • Fatigue1
Skeletal Manifestations
  • Osteoclast activation1
  • Generalized bone mineral density loss9
Immunologic Manifestations
  • Auto-antibody production7
  • Dysregulation of T cells and B cells7,9,10

Elevated IL-6 levels may contribute to anemia, fatigue, and other systemic manifestations of RA.1,2,7

References: 1. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):v3-v11. 2. 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. 3. Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci. 2012;8(9):1227-1236. 4. Hashizume M, Mihara M. The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis. Arthritis. 2011;2011:765624. 5. Trujillo ME, Sullivan S, Harten I, Schneider SH, Greenberg AS, Fried SK. Interleukin-6 regulates human adipose tissue lipid metabolism and leptin production in vitro. J Clin Endocrinol Metab. 2004;89(11):5577-5582. 6. Gierens H, Nauck M, Roth M, et al. Interleukin-6 stimulates LDL receptor gene expression via activation of sterol-responsive and Sp1 binding elements. Arteriorscler Thromb Vasc Biol. 2000;20(7):1777-1783. 7. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24. 8. 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. 9. Maggio M, Guralnik J, Longo DL, Ferrucci L. Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci. 2006;61(6):575-584. 10. de Hooge AS, van De Loo FA, Arntz OJ, van Den Berg WB. Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis. Am J Pathol. 2000;157(6):2081-2091.