Construction and functional analysis of hybrid interleukin‐6 variants Characterization of the role of the C‐terminus for species specificity

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Abstract
We have constructed several hybrid human interleukin‐6 (IL‐6) variants in which the carboxyl‐terminus, which includes a receptor binding site of IL‐6 has been replaced with the C‐terminus of various proteins homologous to human IL‐6, IL‐6 hybrids with the C‐terminus of human growth hormone and human granulocyte‐colony stimulating factor maintain part of the biological activity of human IL‐6. Replacing the C‐terminus of human IL‐6 with the C‐terminus of mouse and rat IL‐6 resulted in a normal or increased activity on a mouse cell line; however, this gave a low (to 200‐fold less) activity on a human cell line compared to wild‐type human IL‐6. We therefore conclude that the C‐terminus of IL‐6 plays in important role in the species specificity of IL‐6.