sgp130

sgp130, short for soluble gp130, is a circulating form of the gp130 signal-transducing subunit of the interleukin-6 (IL-6) receptor family. It is generated by mechanisms such as alternative splicing and proteolytic shedding of the membrane-bound gp130, producing an extracellular domain that is released into the bloodstream. As a soluble receptor, sgp130 participates in dialing the intensity and scope of IL-6 signaling.

In signaling terms, sgp130 binds to the IL-6–soluble IL-6 receptor (IL-6R) complex with high affinity and acts as a natural antagonist of IL-6 trans-signaling. By sequestering this complex, sgp130 prevents activation of gp130 on cells lacking membrane IL-6R, thereby reducing inflammatory signaling that would otherwise propagate through trans-signaling pathways. Importantly, sgp130 does not block classic signaling, which occurs when IL-6 binds membrane-bound IL-6R, allowing some signaling to continue on cells with IL-6R.

Biological significance and therapeutic interest center on its regulatory role in inflammatory responses. Alterations in sgp130 levels have been observed in various disease states, and approaches that modulate sgp130 activity have been explored as potential therapies. A recombinant fusion protein combining sgp130 with an IgG1 Fc fragment, referred to as sgp130Fc, has been studied as a selective inhibitor of IL-6 trans-signaling (often discussed under the name olamkicept). Clinical development has been pursued for several inflammatory conditions, with ongoing research to clarify efficacy and safety profiles.