The short, soluble form of Interleukin-6 receptor alpha (sIL6R), like the longer membrane-associated form IL6RA, binds circulating Interleukin-6 (IL-6). sIL6R is generated by limited proteolysis of the longer membrane associated form and by translation of an alternatively spliced mRNA. The IL-6:sIL6R dimer can associate with the IL6 receptor signaling beta subunit gp130 and stimulate cells that do not express IL6RA, a process termed trans-signaling. Gp130 is widely expressed in many cell types that do not express IL6RA (Rose-John et al. 2006).