Use of HMGB fragments as anti-inflammatory agents
AssigneeNorth Shore-Long Island Jewish Research Institute
InventorsKevin J. Tracey, Huan Yang, Howland Shaw Warren JR., 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.
Claims24
A polypeptide comprising a vertebrate high mobility group box protein (HMGB) A box or a non-naturally occurring HMGB A box which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein.
A polypeptide wherein the polypeptide is a vertebrate high mobility group box protein (HMGB) A box biologically active fragment or a non-naturally occurring HMGB A box biologically active fragment which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein.
A composition comprising a polypeptide comprising a vertebrate high mobility group box protein (HMGB) A box or a non-naturally occurring HMGB A box which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein in a pharmaceutically acceptable excipient.
A composition comprising a polypeptide wherein the polypeptide is a vertebrate high mobility group box protein (HMGB) A box biologically active fragment or a non-naturally occurring HMGB A box biologically active fragment which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein in a pharmaceutically acceptable excipient.
A purified preparation of antibodies that specifically bind to a vertebrate high mobility group box protein (HMGB) B box but do not specifically bind to non-B box epitopes of HMGB, wherein said antibodies can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with HMGB.
A composition comprising a purified preparation of antibodies that specifically bind to a vertebrate high mobility group box protein (HMGB) B box but do not specifically bind to non-B box epitopes of HMGB in a pharmaceutically acceptable excipient, wherein said antibodies can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with HMGB.
A polypeptide comprising a vertebrate high mobility group box protein (HMGB) B box or a non-naturally occurring HMGB B box, but not comprising a full length HMGB protein, wherein said polypeptide can cause release of a proinflammatory cytokine from a vertebrate cell.
A polypeptide wherein the polypeptide is a vertebrate high mobility group box protein (HMGB) B box biologically active fragment or a non-naturally occurring HMGB B box biologically active fragment.
A vector encoding a polypeptide comprising a vertebrate high mobility group box protein (HMGB) B box or a non-naturally occurring HMGB B box, but not comprising a full length HMGB protein, wherein said polypeptide can cause release of a proinflammatory cytokine from a vertebrate cell.
A vector encoding a polypeptide, wherein said polypeptide is a vertebrate high mobility group box protein (HMGB) B box biologically active fragment or a non-naturally occurring HMGB B box biologically active fragment, wherein said polypeptide can cause release of a proinflammatory cytokine from a vertebrate cell.
A method of inhibiting release of a proinflammatory cytokine from a mammalian cell, the method comprising treating the cell with an amount of a purified preparation of antibodies that specifically bind to a vertebrate high mobility group box protein (HMGB) B box but do not specifically bind to non-B box epitopes of HMGB.
A method of inhibiting release of a proinflammatory cytokine from a mammalian cell, the method comprising treating the cell with a polypeptide comprising a vertebrate high mobility group box protein (HMGV) A box or a non-naturally occurring HMGB A box which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein in an amount sufficient to inhibit release of the proinflammatory cytokine from the cell.
A method of inhibiting release of a proinflammatory cytokine from a mammalian cell, the method comprising treating the cell with a polypeptide, wherein said polypeptide is a vertebrate high mobility group box protein (HMGB) A box biologically active fragment or a non-naturally occurring HMGB A box biologically active fragment which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein in an amount sufficient to inhibit release of the proinflammatory cytokine from the cell.
A method of treating a condition in a patient characterized by activation of an inflammatory cytokine cascade, comprising administering to the patient a purified preparation of antibodies that specifically bind to a vertebrate high mobility group box protein (HMGB) B box but do not specifically bind to non-B box epitopes of HMGB, in an amount sufficient to inhibit the inflammatory cytokine cascade.
A method of treating a condition in a patient characterized by activation of an inflammatory cytokine cascade, comprising administering to the patient a polypeptide comprising a vertebrate high mobility group box protein (HMGB) A box or a non-naturally occurring HMGB A box which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein in an amount sufficient to inhibit release of the proinflammatory cytokine from the cell.
A method of treating a condition in a patient characterized by activation of an inflammatory cytokine cascade, comprising administering to the patient a polypeptide, wherein said polypeptide is a vertebrate high mobility group box protein (HMGB) A box biologically active fragment or a non-naturally occurring HMGB A box biologically active fragment which can inhibit release of a proinflammatory cytokine from a vertebrate cell treated with high mobility group box (HMGB) protein in an amount sufficient to inhibit release of the proinflammatory cytokine from the cell.
A method of stimulating the release of a proinflammatory cytokine from a cell comprising treating the cell with a polypeptide comprising a vertebrate high mobility group box protein (HMGB) B box or a non-naturally occurring HMGB B box, but not comprising a full length HMGB polupeptide, in an amount sufficient to stimulate the release of the proinflammatory cytokine from the cell.
A method of stimulating the release of a proinflammatory cytokine from a cell comprising treating the cell with a polypeptide, wherein said polypeptide is a vertebrate high mobility group box protein (HMGB) B box biologically active fragment thereof or a non-naturally occurring HMGB B box biologically active fragment, in an amount sufficient to stimulate the release of the proinflammatory cytokine from the cell.
A method of stimulating the release of a proinflammatory cytokine from a cell comprising treating the cell with a vector encoding a polypeptide comprising a vertebrate high mobility group box protein (HMGB) B box or a non-naturally occurring HMGB B box, but not comprising a full length HMGB, in an amount sufficient to stimulate the release of the proinflammatory cytokine from the cell.
A method of stimulating the release of a proinflammatory cytokine from a cell comprising treating the cell with a vector encoding a polypeptide, wherein said polypeptide is a vertebrate high mobility group box protein (HMGB) B box biologically active fragment or a non-naturally occurring HMGB B box biologically active fragment, in an amount sufficient to stimulate the release of the proinflammatory cytokine from the cell.
A method for effecting weight loss or treating obesity in a patient, comprising administering to the patient an effective amount of a polypeptide comprising a vertebrate high mobility group box protein (HMGB) B box or a non-naturally occurring HMGB B box, but not comprising a full length HMGB polypeptide, in an amount sufficient to stimulate the release of a proinflammatory cytokine from a cell.
A method for effecting weight loss or treating obesity in a patient, comprising administering to the patient an effective amount of a polypeptide, wherein said polypeptide is a vertebrate high mobility group box protein (HMGB) B box biologically active fragment or a non-naturally occurring HMGB B box biologically active fragment, in an amount sufficient to stimulate the release of a proinflammatory cytokine from a cell.
A method of determining whether a compound inhibits inflammation, comprising combining the compound with
- (a) a cell that releases a proinflammatory cytokine when exposed to a vertebrate high mobility group box protein (HMGB) B box;
- and (b) the HMGB B box, then determining whether the compound inhibits the release of the proinflammatory cytokine from the cell.
A method of determining whether a compound inhibits inflammation, comprising combining the compound with
- (a) a cell that releases a proinflammatory cytokine when exposed to a vertebrate high mobility group box protein (HMGB) B box or a biologically active fragment thereof;
- and (b) the HMGB B box or biologically active fragment thereof, then determining whether the compound inhibits the release of the proinflammatory cytokine from the cell.
Dependencies are inferred from the claim text.