Small peptides and methods for treatment of asthma and inflammation

Abstract

A pharmaceutical composition is described as an admixture of a pharmacological carrier and a peptide having the formula f-Met-Leu-X. X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr. Also described are methods for inhibiting the degranulation of mast cells and for treating inflammation in a patient, for example, where the inflammation is a result of a disease selected from the group consisting of asthma, rheumatoid arthritis and anaphylaxis. In addition, methods are described for inhibiting the release of cytokines in a patient, for inhibiting the release of histamines in a patient, for inhibiting the release leukotrienes in a patient, for reducing adhesion, migration and aggregation of lymphocytes, eosinophils and neutrophils to a site of inflammation in a patient, for reducing the production of IgE antibodies at site of inflammation in a patient, and for inhibiting increased vascular permeability at site of inflammation in a patient. The methods use the described pharmaceutical composition.

I claim:  
     
         1 . A pharmaceutical composition comprising a pharmacological carrier and a peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein said peptide is f-Met-Leu-Phe-Phe.  
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said peptide is f-Met-Leu-Tyr.  
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein said carrier is selected for administration of the peptide orally.  
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein said carrier is selected for administration of the peptide by inhalation.  
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein said composition is an aerosol composition.  
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein said carrier is selected for administration of the peptide topically.  
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein said carrier is selected for administration of the peptide by tablet.  
     
     
         9 . A method for inhibiting the degranulation of mast cells, said method comprising contacting the mast cells with a peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         10 . A method for treating asthma in a patient, said method comprising administering to said patient a therapeutically effective amount of a peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         11 . A method for treating inflammation in a patient, said method comprising administering to said patient an anti-inflammation effective amount of a peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         12 . The method of  claim 11 , wherein the inflammation is a result of a disease selected from the group consisting of asthma, rheumatoid arthritis and anaphylaxis.  
     
     
         13 . The method of  claim 11 , wherein the inflammation is a result of rheumatoid arthritis.  
     
     
         14 . The method of  claim 11 , wherein the inflammation is a result of anaphylaxis.  
     
     
         15 . A method for inhibiting the release of cytokines in a patient, said method comprising administering to the patient a cytokine release inhibiting effective amount of peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         16 . A method for inhibiting the release of histamines in a patient, said method comprising administering to the patient a histamine release inhibiting effective amount of peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         17 . A method for inhibiting the release leukotrienes in a patient, said method comprising administering to the patient a leukotriene release inhibiting effective amount of peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         18 . A method for reducing adhesion, migration and aggregation of lymphocytes, eosinophils and neutrophils to a site of inflammation in a patient, said method comprising administering to the patient a inhibiting therapeutically effective amount of a peptide having the formula f-Met-Leu-X where X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         19 . A method for reducing the production of IgE antibodies at site of inflammation in a patient, said method comprising administering to the patient an IgE antibody production inhibiting effective amount of a peptide having the formula f-Met-Leu-X where X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         20 . A method for reducing IgE cross-linking at a site of inflammation in a patient, said method comprising administering to the patient an IgE cross-linking inhibiting effective amount of a peptide having the formula f-Met-Leu-X where X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         21 . A method for inhibiting increased vascular permeability at site of inflammation in a patient, said method comprising administering to the patient a vascular permeability inhibiting effective amount of a peptide having the formula f-Met-Leu-X where X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr.  
     
     
         22 . A method for treating chronic inflammation in a patient, said method comprising administering to the patient an anti-inflammation effective amount of (i) a peptide having the formula f-Met-Leu-X, wherein X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr and (ii) another active ingredient.  
     
     
         23 . The method of claim  24 , wherein the other active ingredient is selected from the group consisting of anti-leukotrienes, beta 2  agonists and corticosteroids.