Interleukin-6 and Interleukin-6 receptor (IL-6 and IL-6R)

Interleukin-6 is a pleiotropic cytokine (small glycoprotein, 185 amino acids, four-helix bundle structure) produced by multiple cell types (immune cells, osteoblasts, endothelial cells, muscle cells)[1][6]. It acts as a pro-inflammatory and anti-inflammatory mediator, driving acute phase response, inflammation, hematopoiesis, bone resorption, and cellular differentiation[4][7]. IL-6 binds to its receptor, the membrane-bound or soluble interleukin-6 receptor (IL-6R, CD126), forming a complex that recruits the ubiquitously expressed gp130 (CD130) signal transducer. The trimeric complex (IL-6, IL-6R, gp130) dimerizes into a hexamer, which activates JAK/STAT signaling and other transcriptional responses[2][3]. Overproduction or dysregulated activity of IL-6/IL-6R is implicated in cancers, autoimmune diseases, severe infections (e.g., COVID-19), and bone disorders[4][7]. Therapeutic targeting focuses on antagonists of the cytokine or receptor, inhibiting the inflammatory signaling pathway[5]. Both IL-6 and IL-6R are regarded as validated drug targets in clinical practice and research.

Other names

IL6human cytokine synthesis inhibitory factorinterferon beta-2B-cell hybridoma growth factorHPGF (hepatocyte stimulating factor)IL-6Rα (for IL-6R, also known as CD126)gp130 (IL-6 signaling subunit, also known as CD130; commonly considered part of IL-6R complex)

Antagonism/neutralization of IL-6 ligand (e.g., siltuximab) Blockade of IL-6R to suppress downstream signaling (e.g., tocilizumab, sarilumab) Inhibition of IL-6-induced JAK/STAT pathway activation Disrupting hexameric complex formation, preventing gp130 dimerization and transcriptional activity