The IL-6 receptor is a heterodimeric complex that consists of a ligand-binding IL-6 receptor α (IL-6Rα) subunit and a signaling component, gp130. Binding of IL-6 to IL-6Rα results in dimerization of receptor with gp130 and subsequent STAT3 activation (1). IL-6Rα is cleaved from the cell surface by ADAM17. In humans, soluble IL-6Rα is also generated via alternatively spliced mRNA. Soluble IL-6Rα binds to IL-6 and can stimulate signaling via membrane bound gp130 in a process known as “trans-signaling”. It is through trans-signaling that IL-6 stimulates cells that do not express membrane bound IL-6Rα.