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

The Interleukin-6 receptor (IL-6R) is a critical mediator of the inflammatory response, composed of a ligand-binding alpha chain (CD126) and a signal-transducing subunit (gp130) (UniProt P08887). It functions through two distinct mechanisms: classic signaling via membrane-bound receptors and trans-signaling via soluble receptors, the latter of which is often associated with pathological inflammation (PubMed PMID: 23233728). Binding of the cytokine IL-6 to the receptor triggers the JAK/STAT3 signaling cascade, promoting the production of acute-phase proteins and the differentiation of immune cells (NCBI Gene ID: 3570). Overactivation of this pathway is implicated in numerous autoimmune diseases, such as rheumatoid arthritis, and life-threatening conditions like cytokine release syndrome (PubMed PMID: 32433946). Consequently, IL-6R is a major therapeutic target, with several approved monoclonal antibodies designed to block its activity and mitigate systemic inflammation (DrugBank DB06273). These drugs, including tocilizumab and sarilumab, bind to both soluble and membrane-bound IL-6R to prevent the formation of the signaling complex.

Other names

IL6RCD126gp80Interleukin-6 receptor subunit alphaIL-6 receptor alpha

Interleukin-6 receptor antagonists bind to the IL-6R alpha subunit, preventing the binding of IL-6 and the subsequent recruitment of gp130, thereby blocking the activation of the JAK/STAT3 signaling pathway (StatPearls, 2023).