A COMPLEX OF THE SOLUBLE INTERLEUKIN-6 RECEPTOR AND INTERLEUKIN-6 IS INTERNALIZED VIA THE SIGNAL TRANSDUCER GP130

In human body fluids a soluble form of the interleukin-6 receptor (sIL -6R) has been found which together with interleukin-6 (IL-6) acts agon istically on cells expressing the signal transducer gp130. The means b y which the sIL-6R is removed from the circulation is unknown. Here, w e show that a complex of I-125-labelled recombinant sIL-6R and IL-6 is internalized by MDCK cells stably transfected with gp130 and by human hepatoma cells HepG2 that endogenously express the IL-6R and gp130. W e further show that most of the internalized sIL-6R is degraded within lysosomes. Our studies suggest that cells expressing gp130 are capabl e of endocytosing an IL-6/s-IL-6R complex, thereby removing both from the circulation.