Development of glycosylated human interleukin-1α, neoglyco IL-1α, by coupling with D-galactose monosaccharide: Biological activities in vitro

In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1α in order to study the effect of glycosylation on its activities, and to develop IL-1 with less deleterious effects. In this study we examined a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on myeloid leukemic cells and melanoma cells, stimulatory effects on IL-6 synthesis by melanoma cells and PGE₂, synthesis by fibroblast cells Galactose-introduced IL-1α (Gal-IL-1α) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1α in all the activities performed in vitro. The competitive binding of ¹²⁵HL-1α to mouse T cells and pre-B cells with unlabeled IL-1α s suggests a decrease in binding affinities of Gal-IL-1α to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1α are due, at least partially, to the decrease in their receptor binding affinities.