Interleukin-6–soluble interleukin-6 receptor–glycoprotein 130 trans-signaling complex (IL-6/sIL-6R/gp130 complex)

The Interleukin-6–soluble interleukin-6 receptor–glycoprotein 130 (IL-6/sIL-6R/gp130) trans-signaling complex is a critical mediator of pro-inflammatory responses in various chronic diseases (Rose-John, S., 2018, PMC). Unlike classic IL-6 signaling, which requires membrane-bound IL-6 receptors (mIL-6R) found only on specific cells like hepatocytes and leukocytes, trans-signaling occurs when IL-6 binds to the soluble form of the receptor (sIL-6R). This binary complex then associates with the ubiquitously expressed glycoprotein 130 (gp130) to initiate signaling in virtually any cell type (Garbers, C., et al., 2018, Nature Reviews Drug Discovery). This pathway is primarily responsible for the pathological, pro-inflammatory effects of IL-6, whereas classic signaling is often associated with regenerative and anti-inflammatory functions (Schreiber, S., et al., 2021, Nature Reviews Gastroenterology & Hepatology). Dysregulation of this complex is a hallmark of conditions such as inflammatory bowel disease, rheumatoid arthritis, and certain cancers (Rose-John, S., 2018, PMC). Therapeutic agents like Olamkicept (sgp130Fc) are designed to selectively inhibit this trans-signaling complex by acting as a decoy for the IL-6/sIL-6R complex, thereby preventing its interaction with membrane-bound gp130 (Zhang, J., et al., 2023, JAMA). This selective approach aims to block chronic inflammation while sparing the homeostatic and protective functions of the classic IL-6 signaling pathway (Garbers, C., et al., 2018, Nature Reviews Drug Discovery).

Other names

IL-6 trans-signaling complexsIL-6R/IL-6/gp130 complexSoluble interleukin-6 receptor trans-signaling complexIL-6/sIL-6R/gp130 hexamer

Selective inhibition of IL-6 trans-signaling by binding to the IL-6/sIL-6R complex and preventing its association with membrane-bound gp130 on the cell surface.