Methods for attenuating release of inflammatory mediators and peptides useful therein

Abstract

The present invention includes methods of inhibiting or suppressing cellular secretory processes. More specifically the present invention relates to inhibiting or reducing the release of inflammatory mediators from inflammatory cells by inhibiting the mechanism associated with the release of inflammatory mediators from granules in inflammatory cells. In this regard, the present invention discloses an intracellular signaling mechanism that illustrates several novel intracellular targets for pharmacological intervention in disorders involving secretion of inflammatory mediators from vesicles in inflammatory cells. Peptide fragments and variants thereof of MANS peptide as disclosed in the present invention are useful in such methods.

I claim: 
     
         1 . A method for inhibiting the production of one or more inflammatory mediators from an inflammatory cell in a tissue and/or fluid of a subject, the method comprising administering to the subject an effective amount of a peptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 106, 1, 11, 37, 45, 79, 91, 93, 108, 121, 124, 141, 143, 153, 219, 234, 239, 248, 241, and 251, wherein the N-terminal amino acid of the peptide is chemically modified by acetylation, and wherein the one or more inflammatory mediators are IL-1beta, IL-8, TNFalpha, or a combination thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject has a respiratory disease. 
     
     
         3 . The method of  claim 2 , wherein the respiratory disease is asthma, chronic bronchitis, chronic obstructive respiratory disease, or acute respiratory distress syndrome (ARDS). 
     
     
         4 . The method of any one of the above claims, wherein the peptide is administered by inhalation, pulmonary administration, or nasal administration. 
     
     
         5 . The method of  claim 1 , wherein the peptide is administered in the form of an aerosol. 
     
     
         6 . The method of  claim 1 , wherein the peptide is administered in the form of a dry powder. 
     
     
         7 . The method of  claim 1 , wherein the peptide is administered by a dry powder inhaler, metered dose inhaler, or nebulizer. 
     
     
         8 . The method of  claim 1 , wherein the subject is a human. 
     
     
         9 . The method of  claim 1 , further comprising administering to the subject a second therapeutic agent selected from the group consisting of an antibiotic, an antiviral compound, an antiparasitic compound, an anti-inflammatory compound, and an immunomodulator. 
     
     
         10 . The method of any one of the above claims, wherein said peptide consists of acetyl-peptide 106 (SEQ ID NO: 106).