Why IL-6 is Important

For U.S. Healthcare Professionals Only

IL-6 is a multifunctional cytokine that may impact the functions of a wide variety of cells and physiologic processes1-4

Normal levels of cytokines and other signaling molecules are requisites for homeostasis with regard to inflammatory processes.1,5 Many cytokines, including tumor necrosis factor-α (TNF-α), interleukins (IL) 1, 4, 6, 12, 13, 17, and 21, and interferons (IFNs), play a pivotal role in inflammatory diseases.1,6

IL-6 represents a critical node in the inflammatory cytokine network. In conditions of autoimmunity and chronic inflammation, elevated levels of IL-6 can disrupt homeostasis in multiple physiologic processes and contribute to chronic inflammation and disease progression.1-4,7-12

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

Immune cells use cytokines and their receptors as tools to communicate and maintain homeostasis or regulate inflammation during infection or trauma.13

Normal levels of IL-6 are vital for homeostasis in the inflammatory process. In response to infection or injury, IL-6 signaling helps promote and coordinate the pro-inflammatory activities of cells throughout the body.1,5,7

  • At sites of infection, IL-6 is released by infiltrating cells of the innate and adaptive immune system, as well as adjacent endothelial cells, stimulating each of these cell types to carry out their respective immune functions14-17
  • IL-6 can promote systemic inflammation through its actions on the liver, which increases hepatic production of acute phase reactants involved in the pro-inflammatory cascade1,18

Under normal conditions, circulating levels of IL-6 are maintained at low levels. Several studies have shown that serum levels of circulating IL-6 in healthy subjects range from ~1 pg/mL to ~16 pg/mL.19-23

However, as one of the central coordinators of the immune response, IL-6 levels are greatly increased in response to infection or trauma. This contributes to increased immune cell survival and proliferation, B-cell antibody production, and a shifting of metabolic function by altering lipid and glucose utilization. Once infection or trauma is resolved, circulating IL-6 levels are restored to basal levels.5,7,8,24-27

Serum IL-6 levels may reach 10,000 pg/mL in response to severe infections, with significant, albeit less dramatic, increases reported in other inflammatory and infectious diseases.22,28,29

  • In patients with rheumatoid arthritis (RA), reports of serum IL-6 levels have varied, ranging from 5 pg/mL to 200 pg/mL, with 100- to 1000-fold higher concentrations found in synovial fluid20,21,29-32

  • In fact, IL-6 is one of the most abundant cytokines in the serum and synovial fluid of the inflamed joints of patients with RA and is associated with disease activity and articular destruction1
Elevated IL-6 levels may affect the homeostasis of a broad range of cells
Elevated IL-6 levels may affect the
homeostasis of a broad range of cells2,24,33-37

Persistently elevated IL-6 may play a role in disrupting homeostasis in multiple physiologic processes

Prolonged elevation of serum IL-6 may have far-reaching effects. In addition to inflammatory effects, elevated IL-6 signaling may also have some impact on metabolism (lipid, glucose), hematopoiesis, the central nervous system, and host defense.5,7-9

In RA, elevated IL-6 levels have been associated with disease activity, articular destruction, and systemic manifestations and may contribute to fatigue, anemia, and the elevated risk of osteoporosis and cardiovascular disease observed in RA patients.1,2,38

Learn more about how IL-6 signaling works

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