The Hyper-IL-6 protein has also been used to explore the physiologic role of Interleukin-6 trans-signaling in vivo. It turned out that this signaling mode was involved in many types of inflammation and cancer.
Hyper-IL-6 has helped to establish the concept of Interleukin-6 trans-signaling. Interleukin-6 trans-signaling mediates the pro-inflammatory activities of Interleukin-6 whereas Interleukin-6 classic signaling governs the protective and regenerative Interleukin-6 activities. Recently, in breast cancer patients, it was shown with the help of Hyper-IL-6 that IL-6 trans-signaling via phosphoinositid-3-kinase signaling activates disseminated cancer cells long before metastases are formed. In addition, it was demonstrated in mice that Hyper-IL-6 transneuronal delivery enabled functional recovery after severe spinal cord injury.