Use of HMGB1 for protection against ischemia reperfusion injury
View Patent ↗Methods and compositions are disclosed for protecting an organ or tissue from inflammation and organ injury following ischemia, reperfusion, and trauma through the administration of an HMGB 1 protein within a time period sufficient to protect the organ or tissue from injury.
1. A method of protecting a heart, liver or a portion of a liver contained within a host animal from injury resulting from controlled ischemia and reperfusion of the heart, liver or a portion of a liver, the method comprising administering to the host animal prior to the initial ischemic insult a mammalian High Mobility Group Box 1 (HMGB1) protein in an amount effective to protect the heart, liver or portion of a liver from injury.
2. The method of claim 1 , wherein the HMGB1 protein comprises a polypeptide having the amino acid sequence of SEQ ID NO:2.
3. The method of claim 1 , wherein the HMGB1 protein consists of a polypeptide having the amino acid sequence of SEQ ID NO:2.
4. The method of claim 1 , wherein the HMGB1 protein is administered about one hour prior to the injury.
5. The method of claim 1 , wherein the HMGB1 protein is administered about 45 minutes prior to the injury.
6. The method of claim 1 , wherein the HMGB1 protein is administered about 30 minutes prior to the injury.
7. The method of claim 1 , wherein the HMGB1 protein is administered about 15 minutes prior to the injury.
8. The method of claim 1 , wherein the HMGB1 protein is administered about 10 minutes prior to the injury.
9. The method of claim 1 , wherein the HMGB1 protein is administered about 5 minutes prior to the injury.
10. The method of claim 1 , wherein the host is a human.
11. The method of claim 1 , wherein the host is a non-human mammal.
12. The method of claim 1 , wherein the HMGB1 protein is administered systemically to the host.
13. The method of claim 1 , wherein the HMGB1 protein is administered by a route selected from the group consisting of intravenous, intramuscular, intraperitoneal, percutaneous, subcutaneous, topical, transmucosal, or oral.
14. The method of claim 1 , wherein the HMGB1 protein is administered locally to the heart, liver or a portion of a liver.
15. The method of claim 1 , wherein the HMGB1 protein is administered in a dosage of about 5 μg to about 35 mg.
16. The method of claim 15 , wherein the HMGB1 protein is administered in a dosage of about 5 μg to about 20 μg.
17. The method of claim 15 , wherein the HMGB1 protein is administered in a dosage of about 20 μg to about 1 mg.
18. The method of claim 15 , wherein the HMGB1 protein is administered in a dosage of about 1 mg to about 10 mg.
19. The method of claim 15 , wherein the HMGB1 protein is administered in a dosage of about 10 mg to about 35 mg.
20. The method of claim 1 , wherein the injury resulting from controlled ischemia and reperfusion occurs during transplantation of the heart, liver or portion of a liver from a donor to a recipient, and wherein the HMGB1 protein is administered to the donor prior to the initial ischemic insult.
21. The method of claim 1 , wherein the ischemia and reperfusion occur during a surgical procedure.
22. The method of claim 1 , wherein the heart, liver or a portion of a liver is a heart.
23. The method of claim 1 , wherein the heart, liver or a portion of a liver is a liver or a portion of a liver.
24. The method of claim 1 , wherein the host animal is a donor of the heart, liver or portion of the liver.
25. The method of claim 24 , wherein the donor is a cadaver donor.
26. The method of claim 24 , wherein the donor is a human.
27. The method of claim 24 , wherein the donor is a non-human mammal.
28. The method of claim 24 , wherein the HMGB1 protein is administered systemically to the donor.
29. The method of claim 1 , wherein the HMGB1 protein is administered locally to the heart, liver or portion of the liver.
30. The method of claim 24 , wherein the HMGB1 protein is administered by a route selected from the group consisting of intravenous, intramuscular, intraperitoneal, percutaneous, subcutaneous, transmucosal, topical, or oral.