Cell death inhibitor

Abstract

The cell death inhibitor comprising a substance capable of binding to macrophage migration inhibitory factor is useful as a preventive/therapeutic agent for, e.g., heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone/joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS, cancer, etc.

1 . A cell death inhibitor comprising a substance capable of binding to macrophage migration inhibitory factor.  
     
     
         2 . The cell death inhibitor according to  claim 1 , wherein the substance capable of binding to a macrophage migration inhibitory factor is an antibody against macrophage migration inhibitory factor.  
     
     
         3 . The cell death inhibitor according to  claim 2 , wherein the antibody is a monoclonal antibody.  
     
     
         4 . The cell death inhibitor according to  claim 1 , wherein the substance capable of binding to macrophage migration inhibitory factor is a compound represented by the formula:  
       
         
           
           
               
               
           
         
       
       wherein R represents a hydrocarbon group which may optionally have one or more substituents, an aromatic heterocyclic group which may optionally have one or more substituents, or an amino group which may optionally have one or more substituents; or a salt thereof.  
     
     
         5 . The cell death inhibitor according to  claim 1 , wherein the substance capable of binding to macrophage migration inhibitory factor is a metalloporphyrin.  
     
     
         6 . The cell death inhibitor according to  claim 1 , wherein the substance capable of binding to macrophage migration inhibitory factor is a substance promoting expression of a gene under control of Antioxidant response element.  
     
     
         7 . The cell death inhibitor according to  claim 1 , wherein the substance capable of binding to macrophage migration inhibitory factor is a substance enhancing the production of a gene protein under control of antioxidant response element.  
     
     
         8 . The cell death inhibitor according to  claim 1 , wherein the substance capable of binding to macrophage migration inhibitory factor is a substance promoting the activity of a gene protein under control of antioxidant response element.  
     
     
         9 . A method of screening a cell death inhibitor, which comprises using macrophage migration inhibitory factor.  
     
     
         10 . The screening method according to  claim 9 , wherein the cell death inhibitor is a substance promoting the expression of a gene under control of antioxidant response element.  
     
     
         11 . The screening method according to  claim 9 , wherein (i) in case that macrophage migration inhibitory factor is mixed with a labeled compound capable of binding to macrophage migration inhibitory factor and (ii) in case that a test compound and macrophage migration inhibitory factor are mixed with the labeled compound capable of binding to macrophage migration inhibitory factor, the binding amounts of the labeled compounds bound to the macrophage migration inhibitory factor are measured in each case, and comparison is made therebetween.  
     
     
         12 . A kit for screening a cell death inhibitor, comprising macrophage migration inhibitory factor.  
     
     
         13 . A method for quantification of macrophage migration inhibitory factor, which comprises using a substance capable of binding to macrophage migration inhibitory factor.  
     
     
         14 . A method for diagnosis of diseases associated with the macrophage migration inhibitory factor, which comprises using the method for quantification according to  claim 13 .  
     
     
         15 . The cell death inhibitor according to  claim 1 , which is an agent for the prevention/treatment of heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone/joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS or cancer, or an agent for protecting transplant organs.  
     
     
         16 . The cell death inhibitor according to  claim 1 , which is an agent for the prevention/treatment of inflammatory bowel diseases.  
     
     
         17 . The cell death inhibitor according to  claim 1 , wherein a HMG-CoA reductase inhibitor, a fibrate-type antihyperlipidemic drug and/or an anticancer agent are/is used in combination.  
     
     
         18 . A method of inhibiting cell death, which comprises administering to a mammal an effective dose of a substance capable of binding to macrophage migration inhibitory factor.  
     
     
         19 . A pharmaceutical composition comprising substance capable of binding to macrophage migration inhibitory factor and a pharmaceutically acceptable carrier.  
     
     
         20 . The method according to  claim 18 , wherein the substance capable of binding to a macrophage migration inhibitory factor is an antibody against macrophage migration inhibitory factor.  
     
     
         21 . The method according to  claim 20 , wherein the antibody is a monoclonal antibody.  
     
     
         22 . The method according to  claim 18 , wherein the substance capable of binding to macrophage migration inhibitory factor is a compound represented by the formula:  
       
         
           
           
               
               
           
         
       
       wherein R represents an optionally substituted hydrocarbon group, an optionally substituted aromatic heterocyclic group, or an optionally substituted amino; or a salt thereof.  
     
     
         23 . The method according to  claim 18 , wherein the substance capable of binding to macrophage migration inhibitory factor is a metalloporphyrin.  
     
     
         24 . The method according to  claim 18 , wherein the substance capable of binding to macrophage migration inhibitory factor is a substance promoting expression of a gene under control of antioxidant response element.  
     
     
         25 . The method according to  claim 18 , wherein the substance capable of binding to macrophage migration inhibitory factor is a substance enhancing the production of a gene protein under control of antioxidant response element.  
     
     
         26 . The method according to  claim 18 , wherein the substance capable of binding to macrophage migration inhibitory factor is a substance promoting the activity of a gene protein under control of antioxidant response element.  
     
     
         27 . The method according to  claim 18 , which is a method for preventing or treating heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone/joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS or cancer, or protecting transplant organs.  
     
     
         28 . The method according to  claim 18 , which is a method for preventing or treating inflammatory bowel diseases.  
     
     
         29 . The method according to  claim 18 , wherein HMG-CoA reductase inhibitor, a fibrate-type antihyperlipidemic drug and/or an anticancer agent are/is used in combination.  
     
     
         30 . A method for preventing or treating a disease selected from the group consisting of heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone/joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS and cancer, or for protecting transplant organs, which comprises administering to a mammal an effective does of the cell death inhibitor according to  claim 1 .  
     
     
         31 . The method according to  claim 30 , wherein the disease is inflammatory bowel diseases.  
     
     
         32 . A method for reducing side effects of a HMG-CoA reductase inhibitor, a fibrate-type antihyperlipidemic drug and/or an anticancer drug, which comprises simultaneously or separately administering to a mammal an effective dose of the cell death inhibitor according to  claim 1  and the HMG-CoA reductase inhibitor, a fibrate-type antihyperlipidemic drug and/or an anticancer drug.  
     
     
         33 . A method of inhibiting cell death, comprising contacting a cell with a cell death inhibitor comprising a substance capable of binding to macrophage migration inhibitory factor.