Method for Preventing and Treating Hyperpermeability

Abstract

A peptide is described, which consists of 7-17 adjacent amino acids and comprises the hexamer TXEXXE, wherein X, X and X can be any natural or non-natural amino acid, wherein the peptide has no TNF receptor binding activity and is cyclized, for the prevention and treatment of hyperpermeability of epithelial cells and endothelial cells.

1 . A method for the prevention of oedema by reduction of hyperpermeability, based on injuries of the endothelium and epithelium layers, comprising the step of:
 administering a peptide consisting the amino acid sequence CGQRETPEGAEAKPWYC (SEQ ID NO: 1) and is cyclized via the C residues in a patient suffering from pneumonia, acute lung injury, acute respiratory distress syndrome (ADRS) or bacterial or viral lung disease.   
     
     
         2 .- 3 . (canceled) 
     
     
         4 . The method according to  claim 1 , wherein the bacterial or viral lung diseases are selected from  Listeria monocytogenes, Streptococcus pneumoniae , SARS viruses, RSV or influenza viruses. 
     
     
         5 . (canceled) 
     
     
         6 . The method according to  claim 1 , wherein the peptide is cyclized via a disulfide bridge between said C residues. 
     
     
         7 . The method according to  claim 1 , wherein the cells of the endothelial layers are protected against hyperpermeability triggered by reactive oxygen molecules. 
     
     
         8 . The method according to  claim 1 , wherein wherein the cells of the endothelial layers are protected against hyperpermeability triggered by bacterial toxins. 
     
     
         9 . The method according to  claim 1 , wherein the phosphorylation of the myosin light chain is inhibited. 
     
     
         10 . The method according to  claim 1 , wherein the peptide is used for inhibiting the activation of protein kinase C. 
     
     
         11 . The method according to  claim 1 , wherein the peptide is used for increasing the expression of the epithelial sodium channel. 
     
     
         12 . The method according to  claim 1 , wherein the peptide is used for treating hyperpermeability triggered by reactive oxygen molecules, microbial toxins, or pulmonary virus infections. 
     
     
         13 . The method according to  claim 1 , wherein the peptide is contained in a pharmaceutical composition comprising the peptide and a pharmaceutical carrier. 
     
     
         14 . A method for the prevention of oedema by reduction of hyperpermeability, based on injuries of the endothelium and epithelium layers, comprising the administration of a peptide consisting the amino acid sequence 7-17 adjacent amino acids and comprising the hexamer TX 1 EX 2 X 3 E, wherein X 1 , X 2  and X 3  can be any natural or non-natural amino acid, wherein the peptide has no TNF receptor binding activity and is cyclized, in a patient suffering from pneumonia, acute lung injury, acute respiratory distress syndrome (ADRS) or bacterial or viral lung disease. 
     
     
         15 . The method according to  claim 14 , wherein peptide comprises the hexamer TPEGAE (SEQ. ID. No. 4). 
     
     
         16 . The method according to  claim 14 , wherein peptide comprises peptide is a cyclized peptide consisting of a sequence of consecutive amino acids selected from the group consisting of 
       
         
           
                 
                 
               
                     
                   (SEQ. ID. No. 5) 
                 
                     
                   QRETPEGAEAKPWY; 
                 
                     
                     
                 
                     
                   (SEQ. ID. No. 6) 
                 
                     
                   PKDTPEGAELKPWY; 
                 
                     
                     
                 
                     
                   (SEQ. ID. No. 7) 
                 
                     
                   CGQRETPEGAEAKPWYC; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ. ID. No. 8) 
                 
                     
                   CGPKDTPEGAELKPWYC; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and fragments of at least 7 amino acids thereof, which fragments include the hexamer TPEGAE. 
     
     
         17 . The method according to  claim 14 , wherein the bacterial or viral lung diseases are selected from  Listeria monocytogenes, Streptococcus pneumoniae , SARS viruses, RSV or influenza viruses. 
     
     
         18 . The method according to  claim 14 , wherein the peptide is cyclized via a disulfide bridge between said C residues. 
     
     
         19 . The method according to  claim 14 , wherein the cells of the endothelial layers are protected against hyperpermeability triggered by reactive oxygen molecules. 
     
     
         20 . The method according to  claim 14 , wherein wherein the cells of the endothelial layers are protected against hyperpermeability triggered by bacterial toxins. 
     
     
         21 . The method according to  claim 14 , wherein the phosphorylation of the myosin light chain is inhibited. 
     
     
         22 . The method according to  claim 14 , wherein the peptide is used for inhibiting the activation of protein kinase C. 
     
     
         23 . The method according to  claim 14 , wherein the peptide is used for increasing the expression of the epithelial sodium channel. 
     
     
         24 . The method according to  claim 14 , wherein the peptide is used for treating hyperpermeability triggered by reactive oxygen molecules, microbial toxins, or pulmonary virus infections. 
     
     
         25 . The method according to  claim 14 , wherein the peptide is contained in a pharmaceutical composition comprising the peptide and a pharmaceutical carrier.