Hyper-IL-6: a highly active designer cytokine consisting of Interleukin-6 (IL-6) and soluble Interleukin-6 receptor (sIL-6R). Molecular model of the fusion protein consisting of IL-6 (gray) and sIL-6R (yellow) fused by a flexible peptide linker (green). A, B, C, and D denote the four helices of IL-6; D-II and D-III are the two cytokinebinding receptor domains of the soluble IL-6R used for the construction of the fusion protein. The fusion protein Hyper-IL-6 is 100-1000 times more active than the separate proteins IL-6 and sIL-6R. Hyper-IL-6 can be used to stimulate several types of target cells, which are not stimulated by IL-6 alone, since they do not express the membrane bound IL-6R. Such cells include embryonic stem cells, endothelial cells, hematopoietic progenitor cells, osteoclasts and neuronal cells.