Takei Y, Chiba T, Wada K, Hayashi H, Yamada M, Kuwashima J, Onozaki K
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
J Interferon Cytokine Res. 1995 Aug;15(8):713-9. doi: 10.1089/jir.1995.15.713.
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.
