PHARMACOKINETICS AND BIOLOGIC ACTIVITIES OF HUMAN NATIVE AND ASIALOINTERFERON-BETA-S

Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in vivo. They are desialylated and taken up by the liver via a n asialoglycoprotein receptor. Fibroblast-derived natural human interf eron-beta is a glycoprotein having a single asparagine-linked sugar ch ain. Although natural human interferon-beta may also be metabolized th rough this pathway, there is very little information about the biologi c features of human asialointerferon-beta. We evaluated the pharmacoki netics and biologic activities of human native and asialointerferon-be ta s. After intravenous administration to rabbits, human asialointerfe ron-beta was cleared from the blood circulation faster than the human native interferon-beta. More asialoprotein was distributed to the live r than the native type, but it induced less 2'5'-oligoadenylate synthe tase. The human asialointerferon-beta had less activity than the human native interferon-beta on cell growth inhibition and 2'5'-oligoadenyl ate synthetase induction in Hep-G2 and HuH6 human hepatoblastoma cells , Southern blotting using a hepatitis B virus-transfected HuH6 cell li ne, HB611, revealed that the inhibition of hepatitis B virus DNA repli cation by the asialoprotein was weaker than that by the native protein . The results showed that the different effects exerted by the human n ative and asialointerferon-beta s may be a result of recognition of th e sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results also suggested that the terminal sialic acid of the sugar chains in natural human interferon-beta significantly affects its pha rmacokinetics and biologic activities.