The short, soluble form of Interleukin-6 receptor alpha (IL6R-2, sIL6R), like the longer membrane-associated form IL6R, binds circulating Interleukin-6 (IL6). IL6R-2 is generated by limited proteolysis of the longer membrane associated form and by translation of an alternatively spliced mRNA. The IL6:IL6R-2 dimer can associate with the IL6 receptor signaling beta subunit IL6ST (gp130) and stimulate cells that do not express IL6R, a process termed trans-signaling. IL6ST is expressed in many cell types that do not express IL6R (Rose-John et al. 2006).