title: Effect of carbohydrates on the pharmacokinetics of human interferon-gamma.
abstract: Human interferon-gamma (IFN-gamma) has two N-linked glycosylation sites at positions 25 and 97 of the 143-amino-acid-long secretory form. To study the role of glycan residues in the pharmacokinetics of IFN-gamma, we produced recombinant IFN-gamma molecules lacking either one or both of the glycosylation sites (Asn mutated to Gln) by baculovirus expression in insect cells. In addition, we produced the fully glycosylated forms both in insect cells and in human leukocyte cultures. Two million units of each IFN were injected intravenously or intramuscularly into rabbits. The glycosylated IFN-gamma molecules from the insect cells were rapidly eliminated from the blood. This is probably due to the fact that their oligosaccharides are of a high mannose type that are rapidly taken up by the liver. The unglycosylated IFN-gamma persisted longer in the blood than the glycosylated recombinant forms. However, the natural IFN-gamma exhibited the longest survival in the blood. The results emphasize the importance of the carbohydrate groups in human IFN-gamma to its pharmacokinetic properties.
authors.affiliation: National Public Health Institute, Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Sareneva
authors.forename: K
authors.initials: K
authors.lastname: Cantell
authors.forename: L
authors.initials: L
authors.lastname: Pyhälä
authors.forename: J
authors.initials: J
authors.lastname: Pirhonen
authors.forename: I
authors.initials: I
authors.lastname: Julkunen
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002478:Cells, Cultured; D006031:Glycosylation; D006801:Humans; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000737:chemistry / Q000493:pharmacokinetics*; D009036:Moths / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry*; D011817:Rabbits; D011994:Recombinant Proteins / Q000493:pharmacokinetics
chemical_list: D011134:Polysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma