Site-specific mutagenesis of human interleukin-6 and its biological activity

AbstractAmino acid substitutions of human interleukin-6 (IL-6) were performed. Single substitution Met162 → Ala and double substitutions Leu159, 166 → Val resulted in a significant decrease of IL-6 activity in the production of immunoglobulin (lg) from B-cells. Single substitution Leu166→Val or Leu159→Val gave a slight or no significant decrease in the Ig-induction activity, respectively. The receptor-binding activity of each IL-6 mutant was also examined. It was observed that the decrease of the receptor-binding activity was generally in parallel with that of the Ig-induction activity. We therefore suggest that hydrophobic side-chains existing in Met162, Leu159, and Leu164 are significantly involved in the receptor-binding of IL-6