POLYETHYLENE-GLYCOL MODIFICATION OF INTERLEUKIN-6 ENHANCES ITS THROMBOPOIETIC ACTIVITY

This study was conducted to increase the in vivo thrombopoietic activi ty of interleukin-6 (IL-6). Recombinant human IL-6 was covalently conj ugated with N-succinimidyl succinate monomethoxy polyethylene glycol ( PEG). The in vitro bioactivity of the PEG-modified IL-6 was reduced wi th increase in its degree of PEG modification, but the in vivo thrombo poietic activity of PEG-modified IL-6 was markedly increased compared to unmodified IL-6. In particular, modified IL-6, in which 54% of the 14 lysine amino groups were coupled with PEG, showed > 10 times greate r thrombopoietic effect in vivo than unmodified IL-6. The area under t he serum concentration curve of PEG-modified n-6 after subcutaneous in jection was > 17 times larger than that of unmodified IL-6. Chemical a ttachment of PEG to IL-6 thus increased the bioavailability of IL-6, a nd may facilitate its potential therapeutic use.