Human hepatocyte-stimulating factor-III and interleukin-6 are structurally and immunologically distinct but regulate the production of the same acute phase plasma proteins.

Human squamous carcinoma (COLO-16) cells synthesize and secrete hepatocyte-stimulating factor-III (HSF-III), a glycoprotein with Mr = 39,000, which stimulates the synthesis of several acute phase plasma proteins in human hepatoma (HepG2) cells. The qualitative response of HepG2 cells to HSF-III is essentially the same as that elicited by human recombinant interleukin-6 (IL-6). Although similar in hepatocyte-stimulating activity, HSF-III and IL-6 are distinct molecules which differ not only in size and charge but also in immunologic properties: no cross-recognition of HSF-III and IL-6 occurs using neutralizing antibodies against IL-6 and HSF-III, respectively. In addition, Northern blot hybridization of IL-6 cDNA to mRNA from COLO-16 cells revealed no detectable IL-6 message. HSF-III does not compete for binding to the IL-6 receptors suggesting that HepG2 cells carry receptors specific for each hormone. Both receptor types may trigger similar intracellular processes explaining the identical regulation of acute phase protein expression.