Compositions and methods to accelerate resolution of acute lung inflammation

Abstract

The present invention provides methods and compositions for treatment of acute inflammatory diseases or disorders and/or for treatment of lung injury. Certain exemplary methods involve administering an IL-4 polypeptide or fragment thereof possessing cytokine activity or an IL-4 agonist systemically to a subject having an inflammatory disease or disorder and/or a lung injury. Other exemplary methods involve administering an inhibitor of DNA methylation systemically to a subject and/or administering an inhibitor of DNA methylation to a cell population comprising T cells (e.g., Treg cells) for introduction/re-introduction to a subject having an inflammatory disease or disorder and/or a lung injury. Compositions and cells for use in such methods are also provided.

1 . A method for treating an acute inflammatory disease or disorder in a subject, the method comprising:
 identifying a subject having an acute inflammatory disease or disorder, and   administering a DNA methyltransferase inhibitor to the subject,   thereby treating the acute inflammatory disease or disorder in the subject; or   
       A method for treating a lung injury in a subject, the method comprising:
 identifying a subject having a lung injury, and 
 administering a DNA methyltransferase inhibitor to the subject, 
 thereby treating the lung injury in the subject; or 
 
       A method for treating influenza in a subject, the method comprising:
 identifying a subject having influenza, and 
 administering a DNA methyltransferase inhibitor to the subject, 
 thereby treating influenza in the subject. 
 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the DNA methyltransferase inhibitor is administered in an amount sufficient to increase Treg frequency in the subject. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the DNA methyltransferase inhibitor is selected from the group consisting of 5-Azacytidine; 5-Aza-2′-deoxycytidine; zebularine; 5-Fluoro-2′-deoxycytidine; 5, 6-Dihydro-5-azacytidine; Hydralazine; Procainamide; Procaine; EGCG ((−)-epigallocatechin-3-gallate); Psammaplin A; MG98; RG108; a DNA methyltransferase-targeting antisense oligonucleotide; and a DNA methyltransferase-targeting RNAi agent. 
     
     
         7 . The method of  claim 1 , wherein the DNA methyltransferase inhibitor is 5-Aza-2′-deoxycytidine. 
     
     
         8 . The method of  claim 1 , wherein the acute inflammatory disease or disorder or lung injury is an acute lung injury. 
     
     
         9 . The method of  claim 1 , wherein the acute inflammatory disease or disorder or lung injury is acute respiratory distress syndrome (ARDS). 
     
     
         10 . The method of  claim 1 , wherein the subject is human. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . A method for treating an acute inflammatory disease or disorder in a subject, the method comprising:
 identifying a subject having an acute inflammatory disease or disorder;   obtaining a population of cells comprising T cells;   administering a DNA methyltransferase inhibitor to the population of cells in vitro, thereby generating a treated population of cells; and   administering the treated population of cells to the subject,   thereby treating the acute inflammatory disease or disorder in the subject.   
     
     
         14 . A method for treating influenza in a subject, the method comprising:
 identifying a subject having influenza;   obtaining a population of cells comprising T cells;   administering a DNA methyltransferase inhibitor to the population of cells in vitro, thereby generating a treated population of cells; and   administering the treated population of cells to the subject,   thereby treating influenza in the subject.   
     
     
         15 - 17 . (canceled) 
     
     
         18 . The method of  claim 13 , wherein the DNA methyltransferase inhibitor is administered in an amount sufficient to increase Treg frequency in the treated population of cells. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 13 , wherein the DNA methyltransferase inhibitor is selected from the group consisting of 5-Azacytidine; 5-Aza-2′-deoxycytidine; zebularine; 5-Fluoro-2′-deoxycytidine; 5, 6-Dihydro-5-azacytidine; Hydralazine; Procainamide; Procaine; EGCG ((−)-epigallocatechin-3-gallate); Psammaplin A; MG98; RG108; a DNA methyltransferase-targeting antisense oligonucleotide; and a DNA methyltransferase-targeting RNAi agent. 
     
     
         21 . The method of  claim 13 , wherein the DNA methyltransferase inhibitor is 5-Aza-2′-deoxycytidine. 
     
     
         22 . The method of  claim 13  wherein the acute inflammatory disease or disorder is an acute lung injury. 
     
     
         23 . The method of  claim 13 , wherein the acute inflammatory disease or disorder is acute respiratory distress syndrome (ARDS). 
     
     
         24 . The method of  claim 13 , wherein the subject is human. 
     
     
         25 . The method of  claim 13 , wherein the treated population of cells is administered to the subject at least 24 hours after a lung injury event in the subject. 
     
     
         26 . The method of  claim 13 , wherein the treated population of cells is administered to the subject within 24 hours after diagnosis of an acute inflammatory disease or disorder, a lung injury event or influenza in the subject. 
     
     
         27 - 51 . (canceled)