IL-6 is a prototypic member of the IL-6 superfamily of cytokines that share gp130 as a
component required for signal transduction (4). The rat, mouse and human IL-6 cDNAs have
been cloned (6-9). Rat IL-6 cDNA encodes a 211 amino acid (aa) residue precursor polypeptide
with a hydrophobic signal peptide that is cleaved to generate the 187 aa residue mature
protein. At the protein sequence level, there is approximately 39% identity between rat and
human, and 87% identity between mouse and rat IL-6 (6). Although human and mouse IL-6 are
equally active on mouse cells, mouse IL-6 is not active on human cells (9).
The high-affinity IL-6 receptor complex, which mediates IL-6 bioactivity, consists of two
membrane glycoproteins: an 80 kDa low-affinity IL-6-binding receptor (IL-6 R) and a 130 kDa
signal-transducing protein (gp130) that lacks IL-6 binding ability (4). The binding of IL-6 to
IL-6 R recruits gp130 to form a trimeric complex that dimerizes to form a hexameric complex,
which transduces IL-6 signal (4). Soluble forms of both IL-6 R and gp130 have been detected in
blood (11, 12). Soluble IL-6 R is capable of binding IL-6 and inducing homodimerization of
membrane gp130 and subsequent signal transduction.
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