Use of HMGB fragments as anti-inflammatory agents
View Patent ↗Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.
1. A pharmaceutical composition comprising a therapeutically effective amount of a polypeptide, an antagonist of TNF and a pharmaceutically acceptable excipient, wherein said polypeptide does not contain an HMGB B box, and wherein said polypeptide inhibits release of a proinflammatory cytokine from a vertebrate cell and comprises an amino acid sequence selected from the group consisting of:
i) an amino acid sequence having at least 80% sequence identity to SEQ ID NO:22;
ii) an amino acid sequence having at least 80% sequence identity to SEQ ID NO:57; and
iii) an amino acid sequence having at least 80% sequence identity to SEQ ID NO:4.
2. The pharmaceutical composition of claim 1 , wherein said polypeptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:22.
3. The pharmaceutical composition of claim 1 , wherein said polypeptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:57.
4. The pharmaceutical composition of claim 1 , wherein said polypeptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:4.
5. A pharmaceutical composition comprising a therapeutically effective amount of a polypeptide, an antagonist of TNF and a pharmaceutically acceptable excipient, wherein said polypeptide does not contain an HMGB B box, and wherein said polypeptide inhibits release of a proinflammatory cytokine from a vertebrate cell and comprises an amino acid sequence selected from the group consisting of:
i) the amino acid sequence of SEQ ID NO:57;
ii) a biologically active fragment of SEQ ID NO:57;
iii) the amino acid sequence of SEQ ID NO:22; and
iv) a biologically active fragment of SEQ ID NO:22.
6. The pharmaceutical composition of claim 5 , wherein said polypeptide comprises the amino acid sequence of SEQ lD NO:57.
7. The pharmaceutical composition of claim 5 , wherein said polypeptide comprises a biologically active fragment of SEQ ID NO:57.
8. The pharmaceutical composition of claim 5 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:22.
9. The pharmaceutical composition of claim 5 , wherein said polypeptide comprises a biologically active fragment of SEQ ID NO:22.
10. A pharmaceutical composition comprising a therapeutically effective amount of a polypeptide and a pharmaceutically acceptable excipient, wherein said polypeptide inhibits release of a proinflammatory cytokine from a vertebrate cell and consists of an amino acid sequence selected from the group consisting of:
i) the amino acid sequence of SEQ ID NO:57;
ii) a biologically active fragment of SEQ ID NO:57;
iii) the amino acid sequence of SEQ ID NO:22; and
iv) a biologically active fragment of SEQ ID NO:22.
11. The pharmaceutical composition of claim 10 , wherein said polypeptide consists of the amino acid sequence of SEQ ID NO:57.
12. The pharmaceutical composition of claim 10 , wherein said polypeptide consists of a biologically active fragment of SEQ ID NO:57.
13. The pharmaceutical composition of claim 12 , wherein said biologically active fragment consists of the amino acid sequence of SEQ ID NO:4.
14. The pharmaceutical composition of claim 10 , wherein said polypeptide consists of the amino acid sequence of SEQ ID NO:22.
15. The pharmaceutical composition of claim 10 , wherein said polypeptide consists of a biologically active fragment of SEQ ID NO:22.
16. The pharmaceutical composition of claim 10 , further comprising an antagonist of TNF.
17. A pharmaceutical composition comprising a therapeutically effective amount of a fusion protein and a pharmaceutically acceptable excipient, wherein said fusion protein comprises a polypeptide, wherein said fusion protein does not contain an HMGB B box, wherein said fusion protein inhibits release of a proinflammatory cytokine from a vertebrate cell, and wherein said polypeptide consists of an amino acid sequence selected from the group consisting of:
i) the amino acid sequence of SEQ ID NO:22;
ii) a biologically active fragment of SEQ ID NO:22;
iii) the amino acid sequence of SEQ ID NO:57;
iv) a biologically active fragment of SEQ ID NO:57; and
v) the amino acid sequence of SEQ ID NO:4.
18. The pharmaceutical composition of claim 17 , wherein said polypeptide consisis of an amino acid sequence selected from the group consisting of SEQ ID NO:22 and a biologically active fragment of SEQ ID NO:22.
19. The pharmaceutical composition of claim 17 , wherein said polypeptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO:57 and a biologically active fragment of SEQ ID NO:57.
20. The pharmaceutical composition of claim 17 , wherein said polypeptide consists of the amino acid sequence of SEQ ID NO:4.