Compositions and methods for treatment of intracellular damage and bacterial infection

Abstract

Pre-implantation factor (PIF) may be used to treat intracellular damage. Aspects of the invention are directed to a method of treating intracellular damage comprising administering PIF to a subject in need thereof. Some aspects may be directed to methods of increasing cytokine secretion in response to intracellular damage comprising administering PIF to a subject in need thereof. The intracellular damage may be a result of a disease such as Listeria monocytogenes infection, malaria, Lyme disease, cardiovascular disease, duodenal peptic ulcer, atherosclerosis, peritonitis or tuberculosis. In some aspects, a method of treating tuberculosis is disclosed, comprising administering PIF to a subject in need thereof. In some aspects, a method of treating atherosclerosis is disclosed, comprising administering PIF to a subject in need thereof. In some aspects, a method of treating peritonitis is disclosed, comprising administering PIF to a subject in need thereof.

1 . A method of treating intracellular damage comprising administering to a subject in need thereof a therapeutically effective amount of a PIF peptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, compositions thereof, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof. 
     
     
         2 . The method of  claim 1  further comprising administering a potassium channel inhibitor. 
     
     
         3 . The method of  claim 2 , wherein the potassium channel inhibitor is a Kv1.3 inhibitor. 
     
     
         4 . The method of  claim 3 , wherein the potassium channel inhibitor is IFNγ. 
     
     
         5 . The method of  claim 1 , wherein the intracellular damage is the result of a disease selected from  Listeria monocytogenes  infection, malaria, Lyme disease, cardiovascular disease, duodenal peptic ulcer, atherosclerosis or tuberculosis. 
     
     
         6 . The method of  claim 1 , wherein the treating further comprises increasing cytokine secretion in response to the intracellular damage. 
     
     
         7 . A method of treating intracellular infection comprising administering to a subject in need thereof a therapeutically effective amount of a PIF peptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, compositions thereof, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof. 
     
     
         8 . The method of  claim 7  further comprising administering a potassium channel inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the potassium channel inhibitor is a Kv1.3 inhibitor. 
     
     
         10 . The method of  claim 8 , wherein the potassium channel inhibitor is IFNγ. 
     
     
         11 . The method of  claim 7 , wherein the intracellular infection is selected from  Listeria monocytogenes, Mycobacterium tuberculosis, Heliobacter pylori, Borrelia burgdorferi sensu stricto, Borelia afzelii , and  Borrelia garinii.    
     
     
         12 . A method of treating peritonitis comprising administering to a subject in need thereof a therapeutically effective amount of a PIF peptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, compositions thereof, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof. 
     
     
         13 . The method of  claim 12  further comprising administering a potassium channel inhibitor. 
     
     
         14 . The method of  claim 13 , wherein the potassium channel inhibitor is a Kv1.3 inhibitor. 
     
     
         15 . The method of  claim 13 , wherein the potassium channel inhibitor is IFNγ. 
     
     
         16 . A method of reducing lipids comprising administering to a subject in need thereof a therapeutically effective amount of a PIF peptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, compositions thereof, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof. 
     
     
         17 . The method of  claim 16  further comprising administering a potassium channel inhibitor. 
     
     
         18 . The method of  claim 17 , wherein the potassium channel inhibitor is a Kv1.3 inhibitor or IFNγ. 
     
     
         19 . The method of  claim 16 , wherein the treating comprises reducing plaque, reducing monocyte proteins, reducing lipids, reducing cytokines and combinations thereof. 
     
     
         20 . The method of  claim 19 , wherein the reducing is completed in an aortic arch, an aortic root and combinations thereof.