WHY IL-6 IS IMPORTANT IN HOMEOSTASIS AND RA

WHY IL-6 IS IMPORTANT IN HOMEOSTASIS AND RA

Through its unique biology, interleukin-6 (IL-6) plays a pivotal role in both immune homeostasis and inflammatory disease1,2

IL-6 activity is mediated through a dual signaling mechanism, expanding its biological impact throughout the body3

Before signaling complex formation and signal transduction are initiated

IL-6 signals through cis-signaling and trans-signaling1,6

IL-6 is a multifunctional cytokine that can influence a wide range of cells and physiologic processes1,3,5

Normal levels of cytokines and other signaling molecules are requisites for homeostasis of inflammatory processes. Many cytokines, including IL-6, play an important role in inflammatory responses and diseases.1,2

Adapted from Choy 2004.

The role of IL-6 in homeostasis and the immune response

IL-6 represents a critical signaling node in the inflammatory cytokine network. Normal levels of IL-6 are vital for homeostasis in the inflammatory process.1-3

  • In response to infection or injury, IL-6 levels are greatly increased locally, helping promote and coordinate the pro-inflammatory activities of cells throughout the body1,3,7,8
    • Increases production of other pro-inflammatory cytokines and antibody production
    • Promotes inflammation
    • Contributes to the innate and adaptive immune responses
  • Under normal physiologic conditions, increased IL-6 expression is immediate and transient; once the infection or trauma is resolved, circulating IL-6 levels are restored to basal levels7,8
  • In conditions of autoimmunity, elevated levels of IL-6 can disrupt homeostasis and contribute to chronic inflammation and disease progression1,7

Persistently high IL-6 levels can disrupt homeostasis in multiple physiological processes1,3

References: 1. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24. 2. McInnes IB. Cytokines. 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; 2013:369-381. 3. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):v3-v11. 4. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012;122(4):143-159. 5. Choy E. Clinical experience with inhibition of interleukin-6. Rheum Dis Clin North Am. 2004;30(2):405-415. 6. Boulanger MJ, Chow D, Brevnova EE, Garcia KC. Hexameric structure and assembly of interleukin-6/IL-6 α-receptor/gp130 complex. Science. 2003;300:2101-2104. 7. 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. 8. 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.

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