Method to increase the number of circulating platelets by administering PEGylated cysteine variants of IL-11

A method to treat an animal to stimulate an increase in circulating platelets in an animal comprising administering to the animal a single effective dose of an IL-11 protein covalently modified with at least one polyethylene glycol (PEG) molecule, wherein the PEGyMated IL-11 protein comprises:

• (a) at least one cysteine residue substituted for an amino acid in IL-11 (SEQ ID NO:17) selected from the group consisting of:
• P22, G23, P24, G27, and A162;
• (b) at least one cysteine residue substituted for an amino acid in IL-11 (SEQ ID NO:17) selected from the group consisting of:
• P24, P25, E38, L39, D69, L72, S74, T77, A114,S117, E123, A148, and S165, and further comprises deletion of amino acid P22 in IL-11 (SEQ ID NO:17);
• (c) at least one non-native cysteine residue which has been added following the C-terminal amino acid of IL-11 (SEQ ID NO:17);
• (d) at least one non-native cysteine residue which has been added following the C-terminal amino acid of IL-11 (SEQ ID NO:17), and further comprises deletion of amino acid P22 in IL -11 (SEQ ID NO:17);
• (e) deletion of one or more amino acids in IL-11 (SEQ ID NO:17) selected from the group consisting of:
• deletion of amino acid P22, deletion of amino acids 22-26 and deletion of amino acids 22-29;
• (f) at least two cysteine substitutions, wherein a cysteine residue is substituted for an amino acid in IL-11 (SEQ ID NO:17) selected from the group consisting of P25 and T77, P25 and S117, P25 and S165, P25 and P24, D69 and T77 and A162 and S165 and further comprises deletion of amino acid P22 in IL-11 (SEQ ID NO:17);
• or
• (g) a PEG molecule attached to at least one amino acid in IL-11 (SEQ ID NO:17) selected from the group consisting of:
• G23, K63, K120, and K196, wherein the protein further comprises a deletion of P22.