Development of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with D-galactose monosaccharide: biological activities in vivo.
In our previous study, a galactose monosaccharide with C9 spacer was chemically coupled to recombinant human interleukin 1alpha (rhIL-1alpha) in order to study the effect of glycosylation on its activities, and to develop IL-1 with less deleterious effects. The glycosylated IL-la exhibited reduced activities in vitro by 10 to 10000-fold depending upon different aspects of activities addressed. The affinity to type I and II IL-1 receptors were also reduced. In this study we examined a variety of IL-1 activities in vivo, including upregulation of serum levels of IL-6, alpha1-acid glycoprotein, NOx, corticosterone, downregulation of serum level of glucose, and recovery of peripheral white blood cells (WBCs) from myelosuppression in 5-fluorouracil-treated mice. In contrast to the biological activities in vitro, these activities in vivo were uniformly reduced by only about 10 to 20-fold compared to untreated IL-1alpha.
Nabeshima
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan.
Chiba
T
T
Takei
Y
Y
Ono
A
A
Moriya
K
K
Onozaki
K
K
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002455:Cell Division; D003345:Corticosterone / Q000097:blood; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005690:Galactose / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007375:Interleukin-1 / Q000031:analogs & derivatives / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D009961:Orosomucoid / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D001786:Blood Glucose; D007375:Interleukin-1; D015850:Interleukin-6; D009961:Orosomucoid; D011994:Recombinant Proteins; D009569:Nitric Oxide; D005472:Fluorouracil; D003345:Corticosterone; D005690:Galactose