Glycosylated human recombinant interleukin-1 alpha, neo interleukin-1 alpha, with D-mannose dimer exhibits selective activities in vivo.
To investigate the effect of carbohydrate-introduction on IL-1 activity, especially in vivo, and to develop IL-1 with less deleterious effects, recombinant human IL-1 alpha was coupled with mannose dimer, alpha-D-Man-1-6-D-Man [Man2 alpha(1-6)] by an acyl azide method. Previous studies demonstrated that the glycosylated IL-1 exhibited reduced activities compared with original IL-1 in all the experiments performed in vitro. In this study, we investigated the in vivo activities of Man2 alpha(1-6)-conjugated IL-1 alpha. The glycosylated IL-1 alpha exhibited very low pyrogenic activity and alpha 1-acid glycoprotein induction compared with untreated IL-1 alpha. Untreated IL-1 alpha increased the serum level of IL-6, but the glycosylated IL-1 alpha did not. However, the glycosylated IL-1 alpha possessed the same potency as untreated IL-1 alpha in reduction of serum levels of glucose and triglyceride and in recovery of peripheral white blood cells in 5-fluorouracil-treated mice. Therefore, glycosylation of IL-1 appeared to be useful for the development of neoIL-1 with selective activity in vivo.
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Y
Y
Takei
T
T
Chiba
K
K
Wada
H
H
Hayashi
M
M
Yamada
J
J
Kuwashima
K
K
Onozaki
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000737:chemistry*; D005260:Female; D006031:Glycosylation; D006801:Humans; D006825:Hybridomas; D007375:Interleukin-1 / Q000737:chemistry / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007962:Leukocytes / Q000187:drug effects; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009961:Orosomucoid / Q000096:biosynthesis; D011749:Pyrogens / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004187:Disaccharides; D007375:Interleukin-1; D015850:Interleukin-6; D009961:Orosomucoid; D011749:Pyrogens; D011994:Recombinant Proteins; D014280:Triglycerides; D008358:Mannose