Methods of treating wounds using IL-23
View Patent ↗Provided are methods of treatment for skin disorders. In particular, treatment, the skin disorders are generally inflammatory skin disorders, including improper wound healing. Provided are methods of using of a cytokine molecule.
1. A method of treating a cutaneous wound comprising administering to a subject an effective amount of an IL-23 complex comprising:
a) a polypeptide comprising residues 352 to 521 of SEQ ID NO: 8 or a conservatively modified variant thereof comprising an individual amino acid substitution; and
b) a polypeptide comprising residues 25 to 330 of SEQ ID NO: 8 or a conservatively modified variant thereof comprising an individual amino acid substitution;
wherein the IL-23 complex increases the expression of IL-17 at least 2-fold in excisional wounds on the backs of C57BI/6NT mice.
2. The method of claim 1 , wherein the wound is an incision wound, an excision wound, an ulcer or a graft.
3. The method of claim 1 , wherein treatment with the IL-23 complex increases:
a) the pressure required to break a healed or healing wound;
b) stiffness of a healed or healed wound;
c) healing rate of the wound;
d) granulation layer thickness of a healed or healing wound;
e) antimicrobial activity in the healed or healing wound; or
f) angiogenesis.
4. The method of claim 1 , wherein treatment with the IL-23 complex increases recruitment of a cell to the wound, and wherein the cell is:
a) a CD11b+ MHC class II cell;
b) a monocyte/macrophage; or
c) a CD31+ endothelial cell.
5. The method of claim 1 , wherein the polypeptide comprising residues 25 to 330 of SEQ ID NO: 8 has no amino acid substitutions.
6. The method of claim 5 , wherein the individual amino acid substitution in the polypeptide comprising residues 352 to 521 of SEQ ID NO: 8 is the exchange of one small amino acid for another small amino acid, wherein the small amino acids are Gly, Ala and Ser.
7. A method of treating a cutaneous wound comprising administering to a subject an effective amount of an IL-23 fusion protein comprising:
a) residues 352 to 521 of SEQ ID NO: 8 or a conservatively modified variant thereof comprising an individual amino acid substitution; and
b) residues 25 to 330 of SEQ ID NO: 8 or a conservatively modified variant thereof comprising an individual amino acid substitution;
wherein the IL-23 fusion protein increases the expression of IL-17 at least 2-fold in excisional wounds on the backs of C57BI/6NT mice.
8. The method of claim 7 , wherein the IL-23 fusion protein comprises residues 25 to 521 of SEQ ID NO: 8 or a conservatively modified variant thereof comprising an individual amino acid substitution.
9. The method of claim 7 , wherein the wound is an incision wound, an excision wound, an ulcer or a graft.
10. The method of claim 7 , wherein treatment with the IL-23 fusion protein increases:
a) the pressure required to break a healed or healing wound;
b) stiffness of a healed or healed wound;
c) healing rate of the wound;
d) granulation layer thickness of a healed or healing wound;
e) antimicrobial activity in the healed or healing wound; or
f) angiogenesis.
11. The method of claim 7 , wherein treatment with the IL-23 fusion protein increases the recruitment of a cell to the wound, and wherein the cell is:
a) a CD11b+ MHC class II cell;
b) a monocyte/macrophage; or
c) a CD31+ endothelial cell.
12. The method of claim 7 , wherein residues 25 to 330 of SEQ ID NO: 8 have no amino acid substitutions.
13. The method of claim 12 , wherein the individual amino acid substitution in residues 352 to 521 of SEQ ID NO: 8 is the exchange of one small amino acid for another small amino acid, wherein the small amino acids are Gly, Ala and Ser.
14. A method of treating a cutaneous wound comprising administering to a subject an effective amount of an IL-23 complex comprising:
a) a polypeptide comprising residues 352 to 521 of SEQ ID NO: 8; and
b) a polypeptide comprising residues 25 to 330 of SEQ ID NO: 8.
15. A method of treating a cutaneous wound comprising administering to a subject an effective amount of an IL-23 fusion protein comprising:
a) residues 352 to 521 of SEQ ID NO: 8; and
b) residues 25 to 330 of SEQ ID NO: 8.