Method of treatment and bioassay involving macrophage migration inhibitory factor (MIF) as cardiac-derived myocardial depressant factor

Abstract

One embodiment of the present invention relates to a pharmaceutical composition, which includes a therapeutically effective amount of at least one anti-MIF antibody; and at least one pharmaceutically acceptable carrier. Another embodiment of the present invention relates to a pharmaceutical composition, which includes a therapeutically effective amount at least one anti-CD74 antibody; and at least one pharmaceutically acceptable carrier. Another embodiment of the present invention relates to a pharmaceutical composition, which includes a therapeutically effective amount of at least one anti-TNFR antibody; a therapeutically effective amount of at least one anti-MIF antibody; and at least one pharmaceutically acceptable carrier. Other embodiments of the present invention relate to methods of treating or preventing cardiac dysfunction, cardiodepression, burn injury-associated cardiac dysfunction, improving cardiac function in a subject following acute myocardial infarction, and identifying an MIF inhibitor.

1 . A pharmaceutical composition effective for at least one selected from the group consisting of treating or preventing cardiac dysfunction in a subject in need thereof, treating or preventing irregularity in myocardial activity in a subject in need thereof, treating or preventing depression in myocardial activity in a subject in need thereof, treating or preventing burn-injury associated cardiac dysfunction in a subject in need thereof, treating or preventing cardiac dysfunction following acute myocardial infarction in a subject in need thereof, treating or preventing cardiodepression in a subject in need thereof, and a combination thereof, comprising: 
 an effective amount of at least one anti-MIF antibody; and    at least one pharmaceutically acceptable carrier.    
     
     
         2 . The pharmaceutical composition of  claim 1 , further comprising at least one CD74 inhibitor.  
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein said CD74 inhibitor comprises at least one anti-CD74 antibody.  
     
     
         4 . A pharmaceutical composition effective for at least one selected from the group consisting of treating or preventing cardiac dysfunction in a subject in need thereof, treating or preventing irregularity in myocardial activity in a subject in need thereof, treating or preventing depression in myocardial activity in a subject in need thereof, treating or preventing burn-injury associated cardiac dysfunction in a subject in need thereof, treating or preventing cardiac dysfunction following acute myocardial infarction in a subject in need thereof, treating or preventing cardiodepression in a subject in need thereof, and a combination thereof, comprising: 
 an effective amount of at least one anti-CD74 antibody, and    at least one pharmaceutically acceptable carrier.    
     
     
         5 . A pharmaceutical composition effective for at least one selected from the group consisting of treating or preventing cardiac dysfunction in a subject in need thereof, treating or preventing irregularity in myocardial activity in a subject in need thereof, treating or preventing depression in myocardial activity in a subject in need thereof, treating or preventing burn-injury associated cardiac dysfunction in a subject in need thereof, treating or preventing cardiac dysfunction following acute myocardial infarction in a subject in need thereof, treating or preventing cardiodepression in a subject in need thereof, and a combination thereof, comprising: 
 an effective amount of at least one anti-TNFR antibody;    an effective amount of at least one anti-MIF antibody; and    at least one pharmaceutically acceptable carrier.    
     
     
         6 . A method for treating or preventing cardiac dysfunction in a subject, said method comprising: 
 administering to said subject an effective amount of at least one anti-MIF antibody.    
     
     
         7 . The method of  claim 6 , wherein said cardiac dysfunction is selected from the group consisting of irregularity in myocardial activity, depression in myocardial activity, and a combination thereof.  
     
     
         8 . A method for treating or preventing burn injury-associated cardiac dysfunction in a subject, said method comprising: 
 administering to said subject an effective amount of at least one anti-MIF antibody.    
     
     
         9 . The method of  claim 8 , wherein said burn injury-associated cardiac dysfunction is selected from the group consisting of irregularity in myocardial activity, depression in myocardial activity, and a combination thereof.  
     
     
         10 . A method for treating or preventing cardiac dysfunction in a subject, said method comprising: 
 administering to said subject an effective amount of at least one anti-CD74 antibody.    
     
     
         11 . A method for improving cardiac function in a subject following acute myocardial infarction, said method comprising: 
 administering to said subject an effective amount of at least one anti-MIF antibody.    
     
     
         12 . A method for at least one selected from the group consisting of treating or preventing cardiac dysfunction in a subject in need thereof, treating or preventing irregularity in myocardial activity in a subject in need thereof, treating or preventing depression in myocardial activity in a subject in need thereof, treating or preventing burn-injury associated cardiac dysfunction in a subject in need thereof, treating or preventing cardiac dysfunction following acute myocardial infarction in a subject in need thereof, treating or preventing cardiodepression in a subject in need thereof, and a combination thereof, comprising administering to a subject in need thereof an effective amount of at least one anti-TNFR antibody; and 
 optionally, at least one pharmaceutically acceptable carrier.    
     
     
         13 . A method for identifying an MIF inhibitor, said method comprising: 
 exposing at least one myocyte to at least one MIF;    determining at least one MIF-related myocyte activity;    exposing said myocyte to said MIF and at least one candidate agent;    determining said MIF-related myocyte activity in the presence of said candidate agent; and    determining whether said candidate agent affects said MIF-related myocyte activity.    
     
     
         14 . A method for treating or preventing or preventing cardiac dysfunction in a subject following acute myocardial infarction, said method comprising: 
 administering to said subject an effective amount of at least one anti-TNFR antibody and an effective amount of at least one anti-MIF antibody.    
     
     
         15 . A method for treating or preventing cardiac dysfunction in a subject, said method comprising: 
 administering to said subject an effective amount of at least one anti-MIF antibody.    
     
     
         16 . A method for treating or preventing burn injury-associated cardiac dysfunction in a subject, said method comprising: 
 administering to said subject an effective amount of a composition comprising at least one anti-MIF antibody and at least one pharmaceutically acceptable carrier.    
     
     
         17 . A method for treating or preventing cardiac dysfunction in a subject, said method comprising: 
 administering to said subject an effective amount of a composition comprising at least one anti-CD74 antibody and at least one pharmaceutically acceptable carrier.    
     
     
         18 . A method for improving cardiac function in a subject following acute myocardial infarction, said method comprising: 
 administering to said subject an effective amount of a composition comprising at least one anti-MIF antibody and at least one pharmaceutically acceptable carrier.    
     
     
         19 . A method for treating or preventing cardiac dysfunction in a subject following acute myocardial infarction, said method comprising: 
 administering to said subject an effective amount of a composition comprising at least one anti-TNFR antibody, at least one anti-MIF antibody, and at least one pharmaceutically acceptable carrier.    
     
     
         20 . A method for at least one selected from the group consisting of treating or preventing cardiac dysfunction in a subject in need thereof, treating or preventing irregularity in myocardial activity in a subject in need thereof, treating or preventing depression in myocardial activity in a subject in need thereof, treating or preventing burn-injury associated cardiac dysfunction in a subject in need thereof, treating or preventing cardiac dysfunction following acute myocardial infarction in a subject in need thereof, treating or preventing cardiodepression in a subject in need thereof, and a combination thereof, comprising administering to said subject an effective amount of at least one selected from the group consisting of small molecule MIF inhibitor, salt thereof, prodrug thereof, and a combination thereof.