Use of HMGB fragments as anti-inflammatory agents
AssigneesThe Feinstein Institute for Medical Research, The General Hospital Corporation, University of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsKevin J. Tracey, Huan Yang, Howland Shaw Warren, Mitchell P. Fink
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Abstract
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.
Claims15
A polypeptide, 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 60% sequence identity to SEQ ID NO:22;
- ii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:57;
- and
- iii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:4.
A composition comprising a polypeptide 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 60% sequence identity to SEQ ID NO:22;
- ii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:57;
- and
- iii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:4.
A vector encoding a polypeptide, 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 60% sequence identity to SEQ ID NO:22;
- ii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:57;
- and
- iii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:4.
A method of treating a condition in a patient characterized by activation of an inflammatory cytokine cascade, comprising administering to the patient a polypeptide which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of:
- i) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:22;
- ii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:57;
- and
- iii) an amino acid sequence having at least 60% sequence identity to SEQ ID NO:4
- in an amount sufficient to inhibit release of the proinflammatory cytokine from the cell.
An antibody or antigen-binding fragment thereof that specifically binds to one or more amino acid sequences selected from the group consisting of SEQ ID NO:5, SEQ ID NO:16, SEQ ID NO:20 and SEQ ID NO:23, and inhibits HMG1-mediated release of a proinflammatory cytokine from a vertebrate cell.
Dependencies are inferred from the claim text.