Inhibition of Classic Signaling Is a Novel Function of Soluble Glycoprotein 130 (sgp130), Which Is Controlled by the Ratio of Interleukin 6 and Soluble Interleukin 6 Receptor

Background: IL-6 trans-signaling plays a critical role in chronic inflammation and cancer. Results: The trans-signaling inhibitor sgp130(Fc) also inhibits classic signaling depending on IL-6/sIL-6R ratios. Conclusion: The additional function of sgp130(Fc) suggests that in vivo only low therapeutic concentrations guarantee blockade of trans-signaling but not classic signaling. Significance: The demonstration that the trans-signaling inhibitor can also inhibit classic signaling is central for the field of IL-6 biology.