Soluble interleukin 6 receptor is biologically active in vivo

A cancer cell transfection model was used to evaluate biological activity of soluble IL-6 receptor (sIL-6R) in vivo. B-78 melanoma cells were stably transfected with cDNAs encoding human IL-6, murine sIL-6R and human leukaemia inhibitory factor (LIF). Control and transfected cells were intravenously (i.v.) and/or subcutaneously (s.c.) injected into B57BL/6 x C3H or SCID mice. Whereas B-78 cells formed tumours and lung metastasis in injected animals, transfected animals, transfected cells showed greatly reduced tumour and metastasis formation. Transfection of IL-6, sIL-6R or LIF had similar protective effects. The combination of IL-6 and sIL-6R was most effective. Kinetic analysis demonstrated a 3 week lag period between formation of tumours by B-78 cells and the combination of B-78 cells transfected with IL-6 and sIL-6R. No such lag phase was seen when B-78-IL-6 or B-78-IL-6 or B-78-sIL-6R were injected alone. These results indicate that IL-6 alone exhibits a different quality of activity when compared to the IL-6-soluble receptor complex. Our results demonstrate for the first time that sIL-6R is a biologically active molecule in vivo.