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

This study was conducted to increase the in vivo thrombopoietic activity of interleukin-6 (IL-6). Recombinant human IL-6 was covalently conjugated with N-succinimidyl succinate monomethoxy polyethylene glycol (PEG). The in vitro bioactivity of the PEG-modified IL-6 was reduced with increase in its degree of PEG modification, but the in vivo thrombopoietic 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 greater thrombopoietic effect in vivo than unmodified IL-6. The area under the serum concentration curve of PEG-modified n-6 after subcutaneous injection was > 17 times larger than that of unmodified IL-6. Chemical attachment of PEG to IL-6 thus increased the bioavailability of IL-6, and may facilitate its potential therapeutic use.