Interleukin-6 (IL-6) signaling axis (IL-6 axis)

The Interleukin-6 (IL-6) signaling axis is a fundamental pathway in the human immune system, responsible for coordinating the pro-inflammatory response, hematopoiesis, and the induction of acute-phase proteins by the liver (Source: UniProt: P05231). Signaling occurs through two primary modes: "classic signaling" via membrane-bound IL-6 receptors (IL-6R) and "trans-signaling" via soluble IL-6R, both of which require the recruitment of the signal-transducing protein gp130 (Source: PubMed: 29038296). Chronic overproduction of IL-6 is implicated in the pathogenesis of numerous autoimmune and inflammatory conditions, including rheumatoid arthritis and cytokine release syndrome, as well as the progression of certain cancers (Source: StatPearls: NBK499840). Therapeutic targeting of this axis has revolutionized the treatment of these disorders, utilizing monoclonal antibodies to either sequester the IL-6 ligand or block the IL-6 receptor. While highly effective, suppression of this axis can impair the body's ability to fight infections and has been associated with rare but serious adverse events like gastrointestinal perforation. Consequently, patients undergoing IL-6 targeted therapy require diligent monitoring of inflammatory markers and hematological profiles.

Other names

IL6B-cell stimulatory factor 2BSF-2Hepatocyte stimulatory factorHSFInterferon beta-2IFNB2CTL differentiation factorCDFHybridoma growth factor

Inhibition of the IL-6 signaling pathway via monoclonal antibodies that either bind directly to the IL-6 cytokine (neutralization) or to the IL-6 receptor (competitive antagonism), preventing the assembly of the IL-6/IL-6R/gp130 signaling complex and subsequent JAK/STAT activation (Source: PubMed: 30204228).