Treatment of liver disease and injury with CXC chemokines
AssigneesThe Regents of the University of Michigan, The University Court of the University of Edinburgh
InventorsCory M. Hogaboam, Cynthia L. Bone-Larson, Kenneth J. Simpson, Nicholas W. Lukacs, Steven L. Kunkel, Lisa M. Colletti, Robert M. Strieter
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Abstract
Disclosed is the surprising discovery that CXC chemokines function to induce rapid hepatocyte proliferation and liver regeneration after injury. The invention thus provides a range of compositions and methods for use in treating liver injury, including those suitable for treating acetaminophen overdose outside the therapeutic window for N-acetyl-cysteine treatment, and those that limit the hepatotoxic side-effects of gene therapy regimens.
Claims51
A method of stimulating hepatocyte proliferation, comprising providing to a hepatocyte at least a first composition comprising at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2) in an amount effective to stimulate hepatocyte proliferation.
A method of stimulating hepatic regeneration, comprising providing to an animal an amount of at least a first CXC chemokine composition effective to activate the CXCR2 receptor, thereby stimulating hepatic regeneration in said animal.
A method of treating an animal with liver damage, comprising administering to said animal at least a first composition comprising at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2);
- wherein said composition is administered in an amount and for a time effective to treat said liver damage in said animal.
A method of treating an animal with liver damage, comprising administering to said animal at least a first ELR-containing CXC chemokine in an amount effective to treat liver damage in said animal.
A method of timely treating a patient with acute liver damage, comprising administering to said patient an amount of at least a first CXC chemokine composition effective to treat acute liver damage in said patient;
- wherein said composition comprises at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2) in said patient and wherein said composition is administered at a time between about ten hours and about 72 hours after the onset of said liver damage.
A method of treating acetaminophen-induced liver damage, comprising administering to a patient with acetaminophen-induced liver damage an amount of at least a first CXC chemokine composition effective to promote liver cell proliferation and liver regeneration in said patient;
- wherein said CXC chemokine composition comprises at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2).
A method of treating an animal with liver damage, comprising administering to said animal an amount of at least a first CXC chemokine composition effective to activate the CXCR2 receptor in said animal, thereby stimulating hepatic regeneration and treating said liver damage in said animal.
A method of treating an animal with liver damage associated with excess acetaminophen or surgical intervention, comprising administering to said animal an amount of at least a first CXC chemokine composition effective to activate the CXCR2 receptor in said animal, thereby stimulating hepatic regeneration and treating said liver damage in said animal.
A method of treating an animal with liver damage, comprising administering to said animal an amount of at least a first ELR-containing CXC chemokine effective to stimulate hepatic regeneration and treat said liver damage in said animal.
A method of stimulating hepatocyte proliferation, comprising providing to a hepatocyte a biologically effective amount of at least a first composition comprising at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2).
A method of treating an animal with liver damage, comprising administering to said animal a therapeutically effective amount of at least a first composition comprising at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2) in said animal.
A method of treating an animal with liver damage, comprising administering to said animal a therapeutically effective amount of at least a first ELR-containing CXC chemokine.
A method of timely treating a patient with acute liver damage, comprising administering to said patient a therapeutically effective amount of at least a first CXC chemokine composition at a time between about ten hours and about 72 hours after the onset of said liver damage;
- wherein said composition comprises at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2) in said patient.
A method of treating acetaminophen-induced liver damage, comprising administering to a patient with acetaminophen-induced liver damage a therapeutically effective amount of at least a first CXC chemokine composition comprising at least a first CXC chemokine that activates the CXC chemokine receptor 2 (CXCR2), thereby promoting liver cell proliferation and liver regeneration in said patient.
A method of stimulating hepatocyte proliferation, comprising providing to a hepatocyte at least a first composition comprising at least a first ELR-containing CXC chemokine selected from the group consisting of MIP-2, ENA-78 and IL-8 in an amount effective to stimulate hepatocyte proliferation.
A method of stimulating hepatic regeneration, comprising providing to an animal at least a first ELR-containing CXC chemokine selected from the group consisting of MIP-2, ENA-78 and IL-8 in an amount effective to activate the CXCR2 receptor, thereby stimulating hepatic regeneration in said animal.
A method of treating an animal with liver damage, comprising administering to said` animal at least a first composition comprising at least a first ELR-containing CXC chemokine selected from the group consisting of MIP-2, ENA-78 and IL-8;
- wherein said composition is administered in an amount and for a time effective to treat said liver damage in said animal.
Dependencies are inferred from the claim text.